Synergistic enhancement of apoptosis by coralyne and paclitaxel in combination on MDA‐MB‐231 a triple‐negative breast cancer cell line

细胞凋亡 癌症研究 紫杉醇 DNA断裂 三阴性乳腺癌 细胞色素c 癌细胞 碎片(计算) 化学 细胞周期 细胞培养 癌症 生物 程序性细胞死亡 乳腺癌 医学 生物化学 内科学 生态学 遗传学
作者
Seema Kumari,Murali G. Mohan,Shailender Gugalavath,Anil Kumar Badana,Rama Rao Malla
出处
期刊:Journal of Cellular Biochemistry [Wiley]
卷期号:120 (10): 18104-18116 被引量:14
标识
DOI:10.1002/jcb.29114
摘要

Abstract Triple‐negative breast cancer (TNBC) is the most outrageous subtype of breast cancer. Emphasizing the urge of new approach in cancer therapy, combinational drug therapy may be proven as an effective strategy. In our previous study, we reported that coralyne (COR) with paclitaxel (PTX) efficiently decreases the proliferation of MDA‐MB‐231 compared with MCF‐7 cell line. Thus, we studied the effect of COR and PTX in combination on apoptosis of MDA‐MB‐231 cell line. In silico results demonstrated that COR intercalates DNA at a minor groove. In vitro approaches revealed that in combination (COR and PTX) increases the efficacy of apoptosis in MDA‐MB‐231 cell line by a significant increase in G1/S phase arrest, DNA fragmentation, and change in mitochondria membrane potential. The expression of ATM and ATR a serine/threonine‐protein kinase, ataxia telangiectasia and Rad3‐related protein were depleted with an increase in time from 24 to 48 hours in concurrent with increased levels of γH2AX indicating that DNA damage routes cells to enter apoptosis. This was confirmed by high levels of caspase‐3 and cytochrome c . Also, the decrease in the expression levels of matrix metalloproteinase‐9 confirmed the antimetastatic efficacy of COR + PTX. The present study indicates that the synergistic effect of COR and PTX can enhance apoptosis in MDA‐MB‐231 cell line and may be proven as a potential anticancer therapy against TNBC.

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