Anticancer Activity of Tetrandrine by Inducing Apoptosis in Human Breast Cancer Cell Line MDA-MB-231 In Vivo

Overview

Journal Evid Based Complement Alternat Med

Specialty Rehabilitation Medicine

Date 2020 Jul 28

PMID 32714412

Citations 9

Authors

Chun-Hui Wang

Jia-Min Yang

Yu-Bo Guo

Jing Shen

Xiao-Hua Pei

Affiliations

Soon will be listed here.

Abstract

Tetrandrine (TET) is an alkaloid extracted from a traditional Chinese medicinal plant. It exerts remarkable anticancer activity and induces apoptotic cell death in various human cancer cells. The present study aimed to investigate the effects of TET on the inhibition of tumor growth and the induction of apoptosis in MDA-MB-231 breast cancer in xenograft mice. Tumor weight and volume were measured. The histopathological changes in the tumor tissue were observed. Immunohistochemistry analysis of Bcl-2-associated X protein (Bax) and B-cell lymphoma/leukemia-2 (Bcl-2) was carried out. The expression of apoptosis-associated genes and proteins, such as cysteine aspartic acid-specific protease-3 (Caspase-3), Survivin, Bax, Bcl-2, BH3-interacting domain death agonist (Bid), and poly ADP-ribose polymerase (PARP), was measured by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, respectively. TET inhibited tumor growth and induced apoptosis in TNBC cell line MDA-MB-231. The mechanism underlying this effect might be mediated by TET-upregulated Caspase-3, Bax, and Bid and downregulated by Bcl-2, Survivin, and PARP. Taken together, this study supported the fact that TET is a promising therapeutic agent for the treatment of TNBC, thereby providing experimental evidence for its use in the treatment of breast cancer.

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References

Min X, Heng H, Yu H, Dan M, Jie C, Zeng Y . Anticancer effects of 10-hydroxycamptothecin induce apoptosis of human osteosarcoma through activating caspase-3, p53 and cytochrome pathways. Oncol Lett. 2018; 15(2):2459-2464. PMC: 5777291. DOI: 10.3892/ol.2017.7610. View

Hou Y, Guo T, Wu C, He X . Effect of tetrandrine combined with epirubicin on the growth of human breast carcinoma multidrug resistance cell line. Yakugaku Zasshi. 2008; 128(4):663-6. DOI: 10.1248/yakushi.128.663. View

Song J, Lan J, Chen C, Hu S, Song J, Liu W . Design, synthesis and bioactivity investigation of tetrandrine derivatives as potential anti-cancer agents. Medchemcomm. 2018; 9(7):1131-1141. PMC: 6072089. DOI: 10.1039/c8md00125a. View

Li Z, Qiu Y, Lu W, Jiang Y, Wang J . Immunotherapeutic interventions of Triple Negative Breast Cancer. J Transl Med. 2018; 16(1):147. PMC: 5977468. DOI: 10.1186/s12967-018-1514-7. View

Gryko M, Pryczynicz A, Zareba K, Kedra B, Kemona A, Guzinska-Ustymowicz K . The expression of Bcl-2 and BID in gastric cancer cells. J Immunol Res. 2014; 2014:953203. PMC: 3987977. DOI: 10.1155/2014/953203. View

Jonges L, Nagelkerke J, Ensink N, van der Velde E, Tollenaar R, Fleuren G . Caspase-3 activity as a prognostic factor in colorectal carcinoma. Lab Invest. 2001; 81(5):681-8. DOI: 10.1038/labinvest.3780277. View

Chen Z, Zhao L, Zhao F, Yang G, Wang J . Tetrandrine suppresses lung cancer growth and induces apoptosis, potentially via the VEGF/HIF-1α/ICAM-1 signaling pathway. Oncol Lett. 2018; 15(5):7433-7437. PMC: 5962877. DOI: 10.3892/ol.2018.8190. View

Yu B, Yuan B, Kiyomi A, Kikuchi H, Hayashi H, Hu X . Differentiation induction of human breast cancer cells by arsenite in combination with tetrandrine. Am J Transl Res. 2020; 11(12):7310-7323. PMC: 6943472. View

Sun X, Xu R, Deng Y, Cheng H, Ma J, Ji J . Effects of tetrandrine on apoptosis and radiosensitivity of nasopharyngeal carcinoma cell line CNE. Acta Biochim Biophys Sin (Shanghai). 2007; 39(11):869-78. DOI: 10.1111/j.1745-7270.2007.00349.x. View

10.

Juan T, Liu K, Kuo C, Yang M, Chu Y, Yang J . Tetrandrine suppresses adhesion, migration and invasion of human colon cancer SW620 cells via inhibition of nuclear factor-κB, matrix metalloproteinase-2 and matrix metalloproteinase-9 signaling pathways. Oncol Lett. 2018; 15(5):7716-7724. PMC: 5921181. DOI: 10.3892/ol.2018.8286. View

11.

Wu G, Liu T, Li H, Li Y, Li D, Li W . c-MYC and reactive oxygen species play roles in tetrandrine-induced leukemia differentiation. Cell Death Dis. 2018; 9(5):473. PMC: 5920096. DOI: 10.1038/s41419-018-0498-9. View

12.

Wang F, Wang J, Zhang Z, Chen S . Tetrandrine inhibits the proliferation and cytokine production induced by IL-22 in HaCaT cells. J Int Med Res. 2018; 46(12):5210-5218. PMC: 6300934. DOI: 10.1177/0300060518801463. View

13.

Wang X, Yang Y, Yang D, Tong G, Lv S, Lin X . Tetrandrine prevents monocrotaline-induced pulmonary arterial hypertension in rats through regulation of the protein expression of inducible nitric oxide synthase and cyclic guanosine monophosphate-dependent protein kinase type 1. J Vasc Surg. 2015; 64(5):1468-1477. DOI: 10.1016/j.jvs.2015.09.016. View

14.

Lin W, Wang W, Lin Y, Leu J, Cheng S, Chen Y . Synergistic effects of tetrandrine combined with ionizing radiation on a murine colorectal carcinoma‑bearing mouse model. Oncol Rep. 2018; 40(3):1390-1400. PMC: 6072404. DOI: 10.3892/or.2018.6568. View

15.

Zhang H, Xie B, Zhang Z, Sheng X, Zhang S . Tetrandrine suppresses cervical cancer growth by inducing apoptosis in vitro and in vivo. Drug Des Devel Ther. 2018; 13:119-127. PMC: 6304242. DOI: 10.2147/DDDT.S187776. View

16.

Lebert J, Lester R, Powell E, Seal M, McCarthy J . Advances in the systemic treatment of triple-negative breast cancer. Curr Oncol. 2018; 25(Suppl 1):S142-S150. PMC: 6001760. DOI: 10.3747/co.25.3954. View

17.

Hsu Y, Chiu Y, Cheng C, Wu C, Lin Y, Huang Y . Antifibrotic effects of tetrandrine on hepatic stellate cells and rats with liver fibrosis. J Gastroenterol Hepatol. 2007; 22(1):99-111. DOI: 10.1111/j.1440-1746.2006.04361.x. View

18.

Adams J, Cory S . The Bcl-2 apoptotic switch in cancer development and therapy. Oncogene. 2007; 26(9):1324-37. PMC: 2930981. DOI: 10.1038/sj.onc.1210220. View

19.

Zhang Z, Liu T, Yu M, Li K, Li W . The plant alkaloid tetrandrine inhibits metastasis via autophagy-dependent Wnt/β-catenin and metastatic tumor antigen 1 signaling in human liver cancer cells. J Exp Clin Cancer Res. 2018; 37(1):7. PMC: 5769468. DOI: 10.1186/s13046-018-0678-6. View

20.

Shine V, Anuja G, Suja S, Raj G, Latha P . Bioassay guided fractionation of Cyclea peltata using in vitro RAW 264.7 cell culture, antioxidant assays and isolation of bioactive compound tetrandrine. J Ayurveda Integr Med. 2018; 11(3):281-286. PMC: 7527820. DOI: 10.1016/j.jaim.2018.05.009. View