Keywords

11.1 Introduction

The World Health Organization (WHO) reported that the lung cancer (lung carcinoma) is one of the main reasons of deaths around the world [1,2,3]. The late diagnosis is the major reason of high casualty rate in lung carcinoma patient, with 70% of cases diagnosed at the final stages. This late diagnosis is the rate determining step in the cancer treatment such as radiotherapy and chemotherapy. The occurrence of lung cancer might be due to environmental factors, genetic factors, and lifestyle. The role of genetic factor is little, while environmental and lifestyle factors have an equal and led role in origin of lung cancer [4, 5]. Ionizing radiation, asbestos, tobacco smoking, sulfur mustard, and coal tar pitch are representative of environmental as well as lifestyle factors and responsible for lung carcinogens. Tobacco smoking is the most dominant threat responsible for lung carcinoma in approximately 80% of women and 90% of men. The lung cancer occurrence rate falls very gradually when the smoking is stopped. This concept is signifying that the person who has stopped the smoking is also the considerable carrier for developing lung cancer [6]. A family history increased the two-fold risk for lung cancer which suggests that genetic factors might play a crucial role in the individual’s susceptibility to lung carcinoma. Though, only smoking is not responsible for lung cancers, the lung cancer patient’s proportion who has by no means smoked may increase in the near future. Exposure to high doses of radiation, air pollution, pre-existing diseases such as tuberculosis or pneumonia and industrial or chemical cancer causing agents such as silica, arsenic, and asbestos also enhanced the risk of developing lung carcinoma. There are other factors like in-house air pollution during cooking also plays an important part for non-smokers especially for women. As a result, besides cessation of smoking, life style adaptation might be a healthy alternative approach for the management of lung carcinoma [7, 8]. Lung carcinoma is a malign lung tissue marked by unrestricted growth of cells in the lung tissue [9]. Metastatis is the process by which cancer cells migrate throughout the body. Primary cancer of lungs is also called as first stage of lung cancer [10]. The survival rate after surgical treatment for non-small cell lung cancer (NSCLC) at earlier stage is much greater than that at the later stage of disease. Unfortunately, lung cancer is mostly recognized at late stages, because the symptoms are not clear and the observation is difficult at stage I and II of NSCLC. Thus, earlier observation of lung cancer is necessary which may lead to more efficacious management of the disease [3]. Increased life span and exposure to new causing agents made it a deadliest disease [11]. Many environmental factors contribute for the development of lung carcinoma in non-smokers. These factors are second-hand tobacco smoke, exposure of gases like polluted air, radon gas, etc. [12].

The basic symptoms of lung cancer are cough and dyspnea [13]. The possible symptoms of lung cancer include pain, cough, blood in sputum, problem in respiratory tract, fatigue, and loss of appetite. Additionally, many studies revealed that patient’s quality of life has been decreased due to more severe form of symptoms. The quality of life has been minimized by the symptoms like pain, loss of appetite, fatigue, dyspnea, etc. [14].

11.2 Epidemiology

The studies on lung cancer have become an extensive subject of interest since last several decades. Lung cancer is more lethal, with greater than 90% mortality rate worldwide [15]. In recent year, the cases of lung cancer were 228,150 and deaths due to this disease was approximately 142,670 as estimated by [16] [17]. It is apparent that genetic and epigenetic pathways are quite different between anti-body drug conjugates and smoking-associated lung cancer. Furthermore, in non-smokers the peripheral cells of bronchioles and alveoli develop the lung cancer. On the other hand, squamous cell carcinomas (SCC), small cell lung cancer, and around 20% of adenocarcinoma developed in the bronchioles [18]. Out of all lung cancer patients, approximately 38.5% suffering from adenocarcinoma, while 20% suffering from squamous cell carcinoma and 2.9% suffering from large cell carcinoma. Since many years, the occurrence of adenocarcinoma has amplified greatly and adenocarcinoma has taken the place of squamous cell carcinoma as the most widespread type of non-small cell lung cancer [19].

Lung cancer detection at the starting point can significantly enlarge the survival chances in 70–90% of patients with non-small cell lung cancer (stage I). A very costly and incursive diagnostic test creates the hindrance in early diagnosis for lung cancer. Hence, mostly patients have reached to later stage when they are diagnosed [20].

In USA, new cases of lung cancer are 12.9% and 5.3 lakh people survive with this disease. Incidence and mortality rate of lung carcinoma are continuously rising, worldwide [17]. The developed countries like Austria and Germany has faced it as a most regular cancer type. In African countries, smoking prevalent cases of lung cancer is low in both men and women, however at global level, lung carcinoma is less ubiquitous in women compared with men. Now the major reason behind the cancer mortality is lung cancer, accounts 1/fifth deaths by cancer in China and death rate is relatively high as compared to the other countries. Death rate in China is estimated to be increased at 40% from 2015 to 2030.

The developed countries such as North America and European countries are facing lung cancer as a common disease in comparison to developing countries like India and South America. Among men and women, lung cancer remains irregular reflecting gender difference of cigarette smoking pattern. Considering the population of women in China, death rate of lung carcinoma is incongruous because of less smoking, and high adenocarcinoma rate [21].

To trace the path, disease aspects and positive outcomes are assessed by epidemiological processes. In the second half of the twentieth century, the main reason behind the mortalities is lung cancer. Although, tobacco consumption remains globally and smoking cigarette resulted in lung cancer [11]. 16 lakh people had been received a new treatment of lung cancer in 2008 [22]. Incidence trend and deaths in the USA among men and women are 11 lakh and 10 lakh, respectively, and mortality is 84,600 in men and 71,340 in women. This represents reductions of cases and deaths in men in 1980. After 1990 and before 2007, there was 28% decline in men death rate. However, incidence of lung cancer increased in women in 1965 and since 2000 onwards, reduction of around 2% has been observed in comparison to the year 1990. Older patients are highly vulnerable to the lung cancer and show 17% mortality. The vulnerability of African, American race in the USA is more from other ethnic groups. Education level gives an inverse relationship between lung cancer and mortality rate. These groups account approximately 25% of total lung cancer patients with 3 lakh mortality per year. The sub groups of female with cell adenocarcinoma have more lung cancer cases, whereas in 30–40% Asian non-smokers patients have lung cancer with respect to 10–20% of Caucasians [12]. Incidence rate of lung cancer between Hispanic and non-Hispanic young white women is higher between the age group of 30 years and 49 years [17]. In India, lung cancer incidence estimated is approximately 70,275 in both genders. It is also the foremost contributor to cancer-related mortality, resulting in 1.38 million cancer deaths per year globally [23].

11.3 Lung CancerTypes

Lung cancer in the lungs emerges out of the epithelium cells of respiratory tract and can be bifurcated into two broad categories. One is small cell lung cancer (SCLC) that is extremely malignant tumor emerges from cells having neuroendocrine characteristics and 15% of total lung cancer cases are suffering from it. Second one is the non-small cell lung cancer which is further separated to three major pathologic sub types: large cell carcinoma, adenocarcinoma, and squamous cell carcinoma.

Smoking plays an important role in squamous type and small cell type carcinoma, but reduction in cases has been observed since 1970. However, non-smoker has the type of carcinoma called adenocarcinoma and shows increase in incidences globally [24]. Nearly, 85% of all cases of lung cancer are NSCLC type. With the decrease in the smoking prevalence, lung cancer has become more frequent among former than current smokers [25]. NSCLC is now defined by pathological characteristics. The two dominant NSCLC histological phenotypes are squamous cell carcinoma (SCC) and adenocarcinoma (ADC). Generally, ADCs arise in more distal ways, however, SCCs arise in more proximal air route and are more strongly associated with smoking and chronic inflammation than ADCs [26].

A 1/third of squamous cell carcinoma is mainly present in boundary of lungs and 2/third is present in central lungs. It shows certain biological features such as intracellular connection, formation of pearl and singular cell of keratinization [27]. This type of NSCLC is causing ulcers in bronchi and more bleeding than any other form, the cancer cells double itself in every 180 days [28].

The adenocarcinoma begins in the central part of lungs, but about 1/fourth develops along the lung boundaries. The tumors are small but the cells double itself in every 180 days. The cancer developed in alveoli is also called as bronchoalveolar adenocarcinoma and may spread in other parts of the lungs through air route [28]. Minimum invasive adenocarcinoma introduced are second and third subtype, whereas the fourth subtype is micropapillary adenocarcinoma, fifth for “mixed subtype” with a greater component generally known as non-mucinous bronchoalveolar adenocarcinoma and lepidic adenocarcinoma is taken as the sixth cancer generally described as mucinous adenocarcinoma, seventh and final. The small biopsy is a cure for adenocarcinoma and diagnostic criteria purposed recommendation for screening of endothelial growth factor receptor alteration and tissue management in adenocarcinoma patients [27].

The large cell carcinoma contributes 3% in lung cancer. This type of cancer present in the lung boundary and regarded as large necrotic cancer. The cells double itself in about every 100 days and can attack the mediastinum during the disease [28]. Clinical trial had shown that different types of cancer give different response to the different treatment. There is no change in the criteria of treatment of large cell carcinoma that occurs by different ways. Non-smoker cell neuroendocrine carcinoma shows (1) Large cell features—big size, polygonal shape, N/C ratio is low, and regular nucleoli. (2) Neuroendocrine features trabecular growth pattern, etc. (3) Frequent necrosis. (4) High multiplication rate [27]. In past few years, in developed countries the cases of SCLC has been declined considerably due to the changes in the formation of cigarette [29].

11.4 Causes of Lung Cancer

The most common cause of lung cancer is cigarette smoking but asbestos and other environmental factors like polluted air and passive smoking are other causes of lung cancer [21]. Gene alteration to DNA and genetic changes are responsible for cancer development. These alterations disrupt the normal functioning of cell including proliferation, cell death pathway, and repairing function. The vulnerability of cancer increases with more damage to the cell [30]. Smoke of cigarette contains minimum 73% well-known carcinogen [31]. Approximately 90% and 70% mortality due to lung cancer in men and women has been observed, respectively, in the developed countries due to smoking [32]. Receptive smoking causes lung cancer to the non-smokers and the risk among the receptive smokers has increased significantly in the countries like United states and European Union. The risk increased by 20–30% for those who live with active smoker than those who works in the surroundings of the second-hand smokers. Tobacco smoke is very much similar to cannabis smoke. It is also reported that marijuana smoke increases the risk of lung cancer by two folds; however, many countries use mixture of both tobacco and cannabis [11, 31]. The various factors affecting the lung cancer include the following:

11.4.1 Smoking of Tobacco

International Agency for Research on Cancer (IARC) reported that there are approximately 4000 chemicals identified in cigarette and out of which 60 chemicals cause cancer. Polycyclic aromatic hydrocarbons (PAHs), aromatic amines, and N-nitrosamines are few of the most potent carcinogens found in the cigarette smoke [33]. Smoking is very dangerous and accountable for 90% mortality in men and 80% deaths among women every year. The smoking has relation with lung cancer in two ways. In first way, mutations in the p53genes are provoked by the polycyclic aromatic hydrocarbons which are responsible and essential for deregulation of cell cycle and carcinogenesis. Within the gene, G to T transversions are linked to a molecular signature of tobacco mutagens in lung cancer caused due to smoking. In second way, the N-nitroso compounds, mainly present in tobacco smoke and are potent animal carcinogens. These compounds also found in the urine of smokers [34].

The inhalation of smoke constistuents not only depends on the cigarette but also on the period and amount of smoking, the presence and proficiency of a filter. The nicotine dependence of the smoker is the primary factor that determines the smoking frequency. The cigarettes nowadays contain not as much of nicotine as in the previous time, but smokers are likely to smoke with higher puffs and frequency to attain a satisfactory level of nicotine. Therefore, the estimation done by smoking machine after measuring the content of tar and nicotine may wrongly estimate individual’s exposure. The incidence of adenocarcinoma is mainly increased by the low yield filtered cigarettes. Hence, the peripheral cells in the bronchi are more exposed to carcinogen in smoke as compared to the other portion of the bronchi. Actually, this peripheral part of the bronchi is deficient in protective epithelium and hence exposed to carcinogens that stimulate adenocarcinoma induction [35].

The extent of lung cancer is directly related to cigarette consumption, nicotine and tar quantity in cigarettes, and utilization of unfiltered cigarettes. Approximately 20% deaths of all cancer deaths all over the world might be prevented just by stopping the tobacco smoking. Around 80% or more lung carcinogenesis merely occurs with exposure to tobacco. Passionate smokers who stop smoking or reduce the smoking keep their nicotine content intake by blocking aeration holes, increasing the retention of smoke in the lungs. This may result in augmented circulation of carcinogens to the lung’s periphery and enhanced incidence of adenocarcinoma [36].

Repeated exposure of lungs to smoking stimulates inflammatory response in lung’s epithelial cells. This leads to the release of chemo static and toxic mediators, reactive oxygen species, and many other pathogenic agents. Such intermediates cause the damage in lung tissues using different mechanisms and promote malignancy. One more marker of lung cancer is cyclooxygenase-2 (COX-2) which regulates the lungs regarding chronic inflammation. It is the marker that is found in malignant and pre-cancerous cells and tells about the signaling of COX-2 for cancer initiation and progression. Smoking also modifies the free radical scavengers in the epithelial cells of lung by way of chronic inflammation induction. In general, reactive oxygen species work as signaling molecules to regulate different pathways. The enhanced generation of reactive oxygen species production in extreme may lead to DNA damage, genetic instability, and replication errors [37].

11.4.2 Genetic Factors

It is found that each and every person who uses tobacco not necessarily develops lung cancer; it indicates that lung malignancy also related to genetics. It may enhance the 1.7-fold risk of lung cancer occurrence in the person having a historical family background with lung cancer. Telomerase reverse transcriptase (TERT) is coded by the 5p15 region and concerned in cell replication. The vulnerability and nicotine dependence for occurrence of lung cancer are related to the 15q25–26 chromosome locus while 6p21 regulates G-protein signaling [38, 39]. Inherited factors contribute about 8% of lung cancers [40]. Many studies have been done on candidate susceptibility of genes that are of high frequency and low penetrance. This approach is presenting the concept that genes are involved in absorption, metabolism, and accumulation of tobacco or carcinogens in tissues of lungs. For instance, many enzymes are involved in the coding of genetic polymorphism for conjugation of tobacco compounds such as aromatic amines, nitrosamines, and polycyclic aromatic hydrocarbons. Phase I (reduction, oxidation, and hydrolysis) and phase II (conjugation) enzymes are involved in the metabolism of these compounds. There are some commonly studied enzymes in this system that include CYP1A1, myeloperoxidase (MPO), the glutathione S-transferases (GST), microsomal epoxide hydrolase 1, and reduced form of nicotinamide adenine dinucleotide phosphate quinine-oxido-reductase 1 [41].

11.4.3 Gender

It is hypothesized that females have more chances of occurrence of lung cancer as compared to males at the equivalent smoking level. Though, analysis of the hypothesis clears that it not correct because studies demonstrate that it is the similar risks for both at specific degree of smoking history. In fact, women show significantly lesser risk of lung cancer as compared to men for a same level of smoking history. It has also been supposed that women are at lesser risk due to fewer exposures to environmental carcinogens. Hence, at the identical smoking level, the risk of occurrence of lung cancer for women appears to same. However, there are some interesting comparisons regarding the lung cancer occurrence between men and women. First, prognosis is better in women having lung cancer than men. Second, the lung cancer occurrence chance may be enhanced by estrogen. Third, there are a few comprehensible gender differences which have noticed in people who never smoked. The percentage of adenocarcinoma in never smoker women is high as compared to men and women who also have a higher frequency of EGFR mutations as compared to men. These observations observed differentiate the gender specifications regarding the lung carcinogenesis and may prove clinically important [42, 43].

11.4.4 Ethnicity and Race

Race has a strong socioeconomic association and is an important and complex variable that affects the lung cancer occurrence. Americans, Hispanics, and Japanese are less susceptible for lung cancer as compared to blacks, Polynesians, and native Hawaiians who are more susceptible. In the United States, it was observed that the mortality and incidence rate are alike among white women, American women, and African, whereas it is 26% higher rate of incidence and 23% higher the mortality rate in American, African men as compared to white men. The susceptibility of mortality due to lung cancer in Cuban Hispanic men is twice as that of Mexican men which is directly related to cultural trend of smoking [16].

11.4.5 Age

DNA break and telomeres shortening are the biological factors that are mainly responsible for the occurrence of cancer in old age. The average age of lung cancer diagnosis for men and women is 70 years. Around 53% of cases are threatened by lung cancer at the age of 55–74 years old and 37% cases are threatened at the age of 75 years old. The approximate data revealed that the lung cancer occurence rate is 586 per 100,000 in the age group of 85–89 years, while it is approximately 366 per 100,000 at the age of 75–79 years in women. The data also showed that about 10% of cases suffer at or less than the age of 55 years. Non-small cell lung cancer studies have been done in patients with age between 20–46 years and it was observed that the females are more prone to adenocarcinoma. In youth, little complexity of disease is observed and hence genetics is the key factor playing a dominant role in this young patient population. The recovery rate in younger patient population is better and they are more susceptible to receive persistent treatment at every point of the disease, while this becomes very typical at the advanced stage of disease [44].

11.4.6 Occupational and Environmental Causes

Around the 1920s, it was the pervasive air quality that was mainly responsible for the occurrence of lung cancer. Mainly, there are two factors that are responsible for indoor and outdoor quality of air: the first one is burning of fossil fuels which lead to the production of carcinogens and particulate matter in the air. The prolonged exposure to such elements leads to the occurrence of occupation related lung carcinoma. Hence, the workers in the trucking industry are associated with 50% increase in the occurrence of lung cancer. Indoor air quality is affected by the burning of unprocessed fossil fuels like biomass fuels and soft coal, cooking and leads to the chances of increase of lung carcinoma. With the maintenance of proper circulation of air in the cooking area may reduce the 50% risk of lung cancer occurrence [45]. Passive smokers are also at the risk of lung cancer occurrence due to the inhalation of a complex smoke mixture and referred to as “second-hand smoke” or “environmental tobacco smoke.”

It is expected that 5–10% of lung cancers patients increase due to occupational exposure. Asbestos is the major and most common lung carcinogen. It is a naturally occurring silicate mineral and amphibole (amosite, trenolite, crocidolite) and serpentine (chrysotile) subtypes. It is a chrysotile fiber that plays an important role in thoracic malignancies occurrence. Exposure to asbestos at the occupational site may increase lung cancer risk five times more. The synergistic effect of tobacco smoking and asbestos exposure boosts the probability of lung cancer [46].

11.4.7 Radon

Ionizing radiations arise from radon (Rn) are responsible as well as the second most leading factor for mortality due to lung carcinoma. Radon contributes approximately 10% of all deaths caused by lung cancer [12]. Environmental Protection Agency reported that radon is the key reason for deaths due to lung cancer. It is also observed that smoking showed the synergistic effect with radon exposure in case of lung cancer occurrence [47]. The disintegration of radioactive radium creates radon gas, which is colorless and odorless gas. Earth’s lithosphere has uranium and decay of uranium produces radium. This radiation decay causes mutations, ionizes genetic material, and becomes cancer causing [48]. When Radon gas concentration increased by 100 bq/m3, it increases the risk of lung carcinoma by 8% or 16% [48]. The level of radon gas changes with change in the crust composition and surrounding.

11.4.8 Asbestos

It is a silicate mineral, occurs naturally and used as a constructing material and insulating material. In countries having larger industrialization, asbestos is present everywhere in the surrounding. Moreover lung cancer caused by exposure to asbestos has a long duration and heaviness [12]. A person having exposure to asbestos has the higher chances of lung cancer than common public [49]. Mesothelioma a type of pleura cancer also caused by asbestos, and this lung cancer is distinct from other lung cancers [50].

11.4.9 Other Causes

The lung cancer has been associated with the number of other factors such as air pollution, gas concentration, radon, genetics works, and surrounding exposure. There are enough proof to show that some cancer causing substances also include aluminum, cadmium and its derivatives, chromium compounds, beryllium and its derivatives, and few combustion products such as coal, coke production, and coal tar pitch. Radiations such as gamma rays, X-rays; Toxic gases such as methyl ether sulfur mustard and fumes from crystalline silica dust and painting having systematic sclerosis pose a little higher lung cancer risk [51].

11.5 Herbal Alternatives for Lung Cancer

At the present time, surgery, radiation, chemotherapy, immunotherapy, and hormones are the chief approaches used together for the cancer treatment. Though chemotherapy is the most used method but a lot of problems are linked with it like severe toxicity, limited efficacy, and multidrug resistance. Plants have been used since ancient time for treatment of cancer and persist to be a chief source of new drugs. Herbal drugs have been documented as smart approach as they have confirmed to be valuable and helpful in sensitizing conventional agents, enhance survival of patient, preventing or reducing the chemotherapy side effects, and life quality improvement in patients of lung cancer. A study conducted on 453 patients of cancer exposed that the approximately 77% of all patients are taking herbal treatment together with conventional chemotherapy. In these cases, the main purpose of using natural products as alternative therapy is to reduce the toxicity, stimulating the immune system, alleviating cancer-related symptoms, and even having direct anticancer effects [52]. Some medicinal herbs with their mechanism of action against lung cancer are listed in Table 11.1 [53].

Table 11.1 Some medicinal herbs with their mechanism of action against lung cancer
Full size table

Chemoprevention is the prophylactic use of non-toxic substances like biological, natural, or synthetic agents for cancer prevention. The occurrence of carcinogenesis is a multifaceted incident and its growth comprises several phases such as initiation, promotion, progression, and lastly metastasis. For instance, in case of lung carcinogenesis, it involves a series of epigenetic and genetic changes in epithelial cells of pulmonary system that direct the cell changes in proliferation, differentiation, invasion, and metastasis. Furthermore, lung carcinogenesis also has “field of cancerization” feature that means tissues near the cancerous lesions would seem to be histologically normal but this tissue has molecular abnormalities at the same time as in the tumors. Example of the “field of cancerization” during lung carcinogenesis is the formation of premalignant in all epithelial cells of airways after exposure to cigarette smoke [54].

This concept is further confirmed because even single mutant epithelial cell in respiratory lining has potential to spread out into surrounding tissues in lung and finally turns into malignancy. Naturally occurring phytochemicals are selectively targeting cancer cells. These chemopreventive phytochemicals play an important role and frequently act on cancer cells even in small doses with no harm on healthy cells. The natural phytochemicals from vegetables and fruits have chemopreventive potentials in case of lung cancer. For example, various studies showed that fruits and vegetables consumption in current smokers may well diminish the risk of occurring lung cancer [55, 56].

Dietary phytochemicals having effective anti-inflammatory or anti-oxidative activities play a vital part in regarding the protection of lung function. Fruits like bananas, apples, and vegetables (tomatoes), fish, herbal tea, white wine, and marine food had shown potential regarding the lung function protection in high risk populations [57].

Tea (Camellia sinensis) is the most regular consumed infusion all over the world. There are many studies which showed that consumption of tea has a protective role on carcinogenesis. The protective effect of green tea on carcinogenesis is mainly due to the presence of epigallocatechin gallate which is a chief component of green tea. It may act through various mechanisms like cell cycle arrest and apoptosis induction, modulation of cell-signaling pathways, modulation of carcinogen metabolizing enzymes, and suppression of the activation of transcription factors that result in the cessation of cancer growth. The epigallocatechin gallate (1–40 μM) inhibits the independent growth of human lung cancer cells by regulating p53 expression and also raises the phosphorylation of p53 at Ser15 and Ser20. It plays an important and major part in the improvement of its transcriptional activity and inhibition of MDM2 mediated p53 ubiquitination [58, 59].

Isothiocyanates are present in cruciferous vegetables as glucosinolates. It is myrosinase enzyme that is responsible for the conversion of glucosinolates to isothiocyanates. Phenethyl isothiocyanate, benzyl isothiocyanate, and sulforaphane are extensively studied for their chemo preventive role beside cancer. The benzyl isothiocyanate inhibited gefitinib resistant human NSCLC cells growth by induction of activation of caspase-3, cell cycle arrest at G2/M phase, apoptosis, generation of reactive oxygen species (ROS), depletion of glutathione, suppression of Akt activity, activation of MAPK, NF-κB transcriptional activation, and activator protein (AP)-1 [60].

Genistein is the most plentiful isoflavone found in soybean and most commonly known for its chemopreventive effects. Genistein (10 μM) has the capacity to enhance trichostatin A apoptosis induction and exert its effect by enhancing the activity of caspase-3 in A549 cells of human lung carcinoma and the normal human lung fibroblasts are unaffected [61].

Fisetin is a naturally occurring flavonoid, occurs in strawberry, grape, persimmon, cucumber, onion, and apple. It has apoptotic, anti-proliferative, and anti-angiogenic properties against cancer cells. Studies had shown that NSCLC cells treatment with fisetin (5–20 μM) restricted cell growth by inhibiting mTOR and PI3K/Akt signaling. It causes declined expression of protein PI3K, phosphorylation of Akt, and mTOR inhibition without affecting normal bronchial epithelial cells [62].

Vitamin C showed the antioxidant activities and found to be protective against lung tissue. Vitamin E is well known for its potent antioxidant property and mainly acts by its membrane repairing, chain breaking, and free radical scavenging activity. The dietary intake of vitamin E is directly correlated with its serum level and lung tissues. A meta-analysis showed that vitamin E and its circulating level is directly associated with lung functioning [63, 64].

Silibinin is a flavonolignan and found mainly as the chief biological active constituent of silymarin. It is mainly extracted from the dried fruits and seeds of Silybum marianum. It plays an important role in the inhibition of initiation and promotion related events in a variety of pre-clinical cancer models for colorectal, skin, lung cancer, and prostate. Among the several cancer models silibinin effects were found to have growth control and prevention of lung cancer through invitro and in vivo studies [65].

Phloretin is a flavonoid that is obtained from apples and other plants such as Pieris japonica, Loiseleuria procumbens, and Hoveniae lignum. It was observed a dose of 125–150 μg/mL of phloretin given against Calu-1, NSCLC cell lines A549, H520, and H838 caused reduction in apoptosis induction, proliferation and suppressing the expression of Bcl-2 while increasing cleaved caspase-3 and 9 protein expressions and also downregulating MMP-2 and 9 expression on gene and protein levels [66]. Some plant drugs having potential against the lung carcinoma, along with their active constituents and mechanism involved are listed in Table 11.2.

Table 11.2 Some reported medicinal plants useful against lung carcinoma
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The compounds like alkaloids, triterpenoids, flavonoids, terpenoids, polysaccharides have been extracted from medicinal plants and some formulas have been combined with chemotherapy for clinical test. Solanum incanum, an alkaloidal drug containing solamargine as active constituent is reported to have potential for treatment of four types of lung cancer. Solamargine therapy enhances the combined activity of TNF alpha and beta to the cancer cells. It makes TNF resistant cell lines that are susceptible to alpha and beta TNF. Besides this, solamargine initiates other cell death processes like release of cytochrome C from mitochondria, decrease the level of antiapoptotic Bcl2, Bcl-xl, increase caspase-3 and fragmentation of DNA, thus showing activity against lung cancer. Triterpenoidal compounds like hederacolchicoside A, extracted from Hedera colchica and beta hedrin obtained from Hedera helix are monodesmoid oleanolic acids and show cytostatic activity against human lung cancer cell line (A549). Bupleurum falcatum contains saikosaponin D as one of its active moiety useful for the liver diseases treatment [96].

The root part of Scutellaria baicalensis Georgi. possesses flavonoidal constituents like wogonin, baicalein, wogonoside, and neobaicalein. These constituents have been reported to stop the growth of malignant cell lines. Baicalein inhibits the activity of lepooxygenase-12 in several forms of cancer [96].

Antofine and acutiaporberine are medicinal plants that have been tested for their anticancer activity. In India, a poly herbal siddha medicine named “Rasagenthi” is used for cancer treatment. In prostate cancer cell line (PC-3), the Rasagenthi chloroform extract induces apoptosis and reduces the growth of these cell lines as per recent studies. It has been reported that the chloroform extract of Rasagenthi has anti carcinogenic activity on lung cancer cell lines. In recent studies, it has been found that the many dietary phytochemical substances have profound antitumor properties [97].

Chinese herbal medicines (CHMs) clinical performance has good response and shows ability to treat different symptoms of lung cancer. Several traditional Chinese medicines formulae affects synergistically as herb extracts have been reported to stop lung cancer at various stages. It also prevents the patient from adverse side effects of single drug. Research demonstrates that Chinese treatment helps the body to fight against infectious agents that increases the patient’s life. Various types of chemical compounds like triterpenoids, alkaloids, terpenoids, flavonoids, and polysaccharides have been reported to possess activity against lung carcinoma [96].

11.6 Conclusion

The traditional ways of treatment using herbal medicinal products are being used for centuries in the treatment of various types of disease. As one of the attractive alternatives to lung cancer treatment, herbal medicines have been recognized and proved to be useful and effective in sensitizing conventional agents, prolonging patient survival, preventing chemotherapy side effects, and enhancing the quality of life of patients with lung cancer. The natural products were primarily used as alternative therapy for the treatment with the goal of reducing toxicity, alleviating symptoms associated with cancer, enhancing the immune system, and also having direct effects on cancer. Herbal treatment has been considered as additional treatment for some malignant disease based on recent scientific research on herbs. Even though several studies have shown an assessment of the potential mechanisms of action of these compounds, many studies have still provided only preliminary screening data and therefore not identified their mechanism of action.