Abstract
Tanshinone IIA, a diterpene quinone extracted from the traditional herbal medicine, Salvia miltiorrhiza Bunge, is used widely and successfully in clinics in China for treating inflammatory diseases. Recently tanshinone IIA has been reported to have apoptosis inducing effects on a large variety of cancer cells. In this study, the anti-proliferation and apoptosis inducing effects of tanshinone IIA as well as its influence on cell adhesion to and invasion through the extracellular matrix (ECM) on acute promyelocytic leukemia (APL) NB4 cells in vitro were studied. Cell proliferation was assessed by MTT assay, cell apoptosis was observed by Hoechst 33258 staining and flow cytometry (FCM); The variation of caspase-3 and apoptotic related genes were assayed by Western blotting, cell mitochondrial membrane potential as well as cell adhesive and invasive effects were also investigated by using standard methods. The results showed that tanshinone IIA exhibited induction of apoptosis by activation of caspase-3, downregulation of anti-apoptotic protein bcl-2 and bcl-xl and upregulation of pro-apoptotic protein bax, as well as disruption of the mitochondrial membrane potential. Furthermore, treatment by tanshinone IIA could reduce cell adhesion to and invasion through ECM in leukemia NB4 cells. These data provide a potential mechanism for tanshinone IIA-induced apoptosis and cell growth inhibition in leukemia NB4 cells, suggesting that tanshinone IIA may serve as an effective adjunctive reagent for the treatment of APL.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Jabbour E.J., Estey E., Kantarjian H.M. (2006). Adult acute myeloid leukemia. Mayo. Clin. Proc. 81:247–260
Macheta M., Yin J.A. (2001). Recent advances in the treatment of AML. Hematol. Oncol. 19:107–118
Lengfelder E., Saussele S., Weisser A., Buchner T., Hehlmann R. (2005). Treatment concepts of acute promyelocytic leukemia. Crit. Rev. Oncol. Hematol. 56:261–274
Boon H., Wong J. (2004). Botanical medicine and cancer: a review of the safety and efficacy. Expert. Opin. Pharmacother. 5:2485–2501
Zhou L., Zuo Z., Chow M.S. (2005). Danshen: an overview of its chemistry, pharmacology, pharmacokinetics, and clinical use. J. Clin. Pharmacol. 45:1345–1359
Wang A.M., Sha S.H., Lesniak W., Schacht J. (2003). Tanshinone (Salviae miltiorrhizae extract) preparations attenuate aminoglycoside-induced free radical formation in vitro and ototoxicity in vivo. Antimicrob. Agents Chemother. 47:1836–1841
Yang L.J., Jeng C.J., Kung H.N., Chang C.C., Wang A.G., Chau G.Y., Don M.J., Chau Y.P., (2005). Tanshinone IIA isolated from Salvia miltiorrhiza elicits the cell death of human endothelial cells. J. Biomed. Sci. 12:347–361
Choi H.S., Cho D.I., Choi H.K., Im S.Y., Ryu S.Y., Kim K.M. (2004). Molecular mechanisms of inhibitory activities of tanshinones on lipopolysaccharide-induced nitric oxide generation in RAW 264.7 cells. Arch. Pharm. Res. 27:1233–1237
Wang X., Wei Y., Yuan S., Liu G., Lu Y., Zhang J., Wang W. (2005). Potential anticancer activity of tanshinone IIA against human breast cancer. Int. J. Cancer. 116:799–807
Yuan S.L., Wei Y.Q., Wang X.J., Xiao F., Li S.F., Zhang J. (2004). Growth inhibition and apoptosis induction of tanshinone II-A on human hepatocellular carcinoma cells. World J. Gastroenterol. 10:2024–2028
Treasure J. (2005). Herbal medicine and cancer: an introductory overview. Semin. Oncol. Nurs. 21:177–183
Chan T.Y. (2001). Interaction between warfarin and danshen (Salvia miltiorrhiza). Ann. Pharmacol. 35:501–504
Yokozawa T., Chen C.P. (2000). Role of Salvia miltiorrhiza radix extract and its compounds in enhancing nitric oxide expression. Phytomedicine 7:55–61
Zhou G.Y., Zhao B.L., Hou J.W., Ma G.E., Xin W.J. (1999). Protective effects of sodium tanshinone IIA sulphonate against adriamycin-induced lipid peroxidation in mice hearts in vivo and in vitro. Pharmacol. Res. 40:487–491
Mosaddik M.A. (2003). In vitro cytotoxicity of tanshinones isolated from Salvia miltiorrhiza Bunge against P388 lymphocytic leukemia cells. Phytomedicine 10:682–685
Vasiliev J.M. (2004). Cytoskeletal mechanisms responsible for invasive migration of neoplastic cells. Int. J. Dev. Biol. 48:425–439
Simpson-Haidaris P.J., Rybarczyk B. (2001). Tumors and fibrinogen. The role of fibrinogen as an extracellular matrix protein. Ann. N.Y. Acad. Sci. 936:406–425
Yu X.F., Han Z.C. (2006). Matrix metalloproteinases in bone marrow: roles of gelatinases in physiological hematopoiesis and hematopoietic malignancies. Histol. Histopathol. 21:519–531
Denault J.B., Salvesen G.S. (2002). Caspases: keys in the ignition of cell death. Chem. Rev. 102:4489–4500
Philchenkov A.A. (2003). Caspases as regulators of apoptosis and other cell functions. Biochemistry 68:365–376
Smolewski P., Darzynkiewicz Z., Robak T. (2003). Caspase-mediated cell death in hematological malignancies: theoretical considerations, methods of assessment, and clinical implications. Leuk. Lymphoma 44:1089–1104
Kirkin V., Joos S., Zornig M. (2004). The role of Bcl-2 family members in tumorigenesis. Biochim. Biophys. Acta 1644:229–249
Wang S., Yang D., Lippman M.E. (2003). Targeting Bcl-2 and Bcl-XL with nonpeptidic small-molecule antagonists. Semin. Oncol. 30(S16):133–142
Sharpe J.C., Arnoult D., Youle R.J. (2004). Control of mitochondrial permeability by Bcl-2 family members. Biochim. Biophys. Acta 1644:107–113
Acknowledgements
We thank post-doctoral fellow Liu DJ for help with computer analysis and presentation of data. We also thank the members of our laboratories for their insight and technical support. This work is supported by the grants from National Natural Foundation of China (No. 30570786, No. 30472022).
Author information
Authors and Affiliations
Corresponding author
Additional information
Contributed equally to this study.
Rights and permissions
About this article
Cite this article
Liu, JJ., Lin, DJ., Liu, PQ. et al. Induction of apoptosis and inhibition of cell adhesive and invasive effects by tanshinone IIA in acute promyelocytic leukemia cells in vitro . J Biomed Sci 13, 813–823 (2006). https://doi.org/10.1007/s11373-006-9110-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11373-006-9110-x