Inhibition of isofraxidin from sarcandra glabra on the breast cancer stem cells via Bcl-2 and Caspase signaling pathway

doi:10.12092/j.issn.1009-2501.2018.08.008

Abstract

Abstract:

AIM: To investigate the effects of isofraxidin from sarcandra glabra on the expression levels of Bcl-2, Caspase-3 and Caspase-8 which are related with the apoptosis in breast cancer stem cells. METHODS: The breast cancer stem-like cells were enriched from MDA-MB-231 cell lines using the serum-free culture method, and the CD44⁺/CD24 ^-/low subpopulation was sorted using the flow cytometry. After 0, 17, 50, 150 and 450 μmol/L isofraxidin were administrated to each group, the cell viability were detected using CCK-8 reagent, the width of cell wound was continuously recorded via microscopic photograph, and the total cell apoptosis rates were recorded using Annexin V-FITC/PI staining. The mRNA and protein levels of Bcl-2, Caspase-3 and Caspase-8 were measured using Real-time quantitative PCR and Western blot, respectively. RESULTS: Significantly lower rates of proliferation were observed in 50, 150, and 450 μmol/L isofraxidin group at 24, 48 and 72 h. 50, 150 and 450 μmol/L isofraxidin given for 48 h results in the decline of cell migration and increase in the rate of apoptotic. For the levels of mRNA and protein, Bcl-2 gene of 50, 150 and 450 μmol/L group was higher than that of the control, nevertheless, caspase-3 and caspase-8 gene of these groups were lower than those of the control. All the data showed a clear-cut dose-effect relationship. CONCLUSION: The up-regulation of Bcl-2 and the down-regulation of Casepase-3/8 genes are related with the apoptosis, proliferation inhibition and reduced migration of breast cancer stem cells after isofraxidin treatment.

Key words: isofraxidin, tumor stem cells, WST-8, apoptosis, Bcl-2, Caspase

CLC Number:

R965.2

LI Hong, CHEN Jing, LI Dan, YU Wentao, LIU Zhengwei, NI Feng. Inhibition of isofraxidin from sarcandra glabra on the breast cancer stem cells via Bcl-2 and Caspase signaling pathway[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(8): 886-892.

References

［1］Tsai YC，Chen SH，Lin LC，et al. Anti-inflammatory principles from sarcandra glabra［J］. J Agric Food Chem, 2017, 65(31): 6497-6505.
［2］朱晓莹，李韬，李盛毅，等. 肿节风复方含药血清对肝癌HepG2细胞增殖、端粒酶及凋亡的影响［J］.中国实验方剂学杂志, 2014, 20(2): 109-112.
［3］Chou ST, Peng HY, Chang CT，et al. Zanthoxylum ailanthoides Sieb and Zucc. extract inhibits growth and induces cell death through G2/M-phase arrest and activation of apoptotic signals in colo 205 human colon adenocarcinoma cells［J］. Anticancer Res, 2011, 31(5): 1667-1676.
［4］Yamazaki T, Tokiwa T. Isofraxidin, a coumarin component from Acanthopanax senticosus, inhibits matrix metalloproteinase-7 expression and cell invasion of human hepatoma cells［J］. Biol Pharm Bull, 2010, 33(10): 1716-1722.
［5］石建伟，唐智柳，蔡美玉，等. 2008～2012年我国女性乳腺癌流行状况的系统性综述［J］. 中国妇幼保健, 2014, 29(10): 1622-1626.
［6］Neophytou C，Boutsikos P, Papageorgis P. Molecular mechanisms and emerging therapeutic targets of triple-negative breast cancer metastasis［J］. Front Oncol, 2018, 8: 31.
［7］Al-Hajj M，Clarke MF. Self-renewal and solid tumor stem cells［J］. Oncogene, 2004, 23(43): 7274-7282.
［8］Mohammadpour F, Ostad SN, Aliebrahimi S，et al. Anti-invasion effects of cannabinoids agonist and antagonist on human breast cancer stem cells［J］. Iran J Pharm Res, 2017, 16(4): 1479-1486.
［9］蔡加琴，魏晓霞，黄旭慧，等. 氧化苦参碱通过调控上皮间质转化抑制三阴性乳腺癌细胞侵袭转移［J］. 中国临床药理学与治疗学, 2018, 23(1): 13-17.
［10］Fan P，Fan S，Wang H，et al. Genistein decreases the breast cancer stem-like cell population through Hedgehog pathway［J］. Stem Cell Res Ther, 2013, 4(6): 146.
［11］Zhou QM, Sun Y, Lu YY，et al. Curcumin reduces mitomycin C resistance in breast cancer stem cells by regulating Bcl-2 family-mediated apoptosis［J］. Cancer Cell Int, 2017, 17: 84.
［12］李学农. 草珊瑚醇提物抗肿瘤有效部位的HPLC分离及各分离组分体外抗肿瘤作用的实验研究［J］. 海峡药学, 2013, 25(8): 184-185.
［13］Qu Y，Lin Q，Yuan Y，et al. Cyclosporin A inhibits adipogenic differentiation and regulates immunomodulatory functions of murine mesenchymal stem cells［J］. Biochem Biophys Res Commun, 2018, 498(3): 516-522.
［14］周齐. 百里醌抑制体外骨肉瘤细胞转移的实验研究［J］. 中国医学创新, 2016, 13(5): 26-29.
［15］Hu Y，Yague E, Zhao J，et al. Sabutoclax, pan-active BCL-2 protein family antagonist, overcomes drug resistance and eliminates cancer stem cells in breast cancer［J］. Cancer Lett, 2018, 423: 47-59.
［16］Shen P, Wang HG, Li MM，et al. Isofraxidin inhibited proliferation and induced apoptosis via blockage of Akt pathway in human colorectal cancer cells［J］. Biomed Pharmacother, 2017, 92: 78-85.

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