An anti-cancerous protein fraction from Withania somnifera induces ROS-dependent mitochondria-mediated apoptosis in human MDA-MB-231 breast cancer cells

被引:32
作者
Dar, Parvaiz A. [1 ]
Mir, Sameer A. [2 ]
Bhat, Javeed A. [2 ]
Hamid, Abid [3 ]
Singh, Laishram R. [4 ]
Malik, Fayaz [2 ]
Dar, Tanveer A. [1 ]
机构
[1] Univ Kashmir, Dept Clin Biochem, Srinagar, Jammu & Kashmir, India
[2] CSIR IIIM, Canc Pharmacol Div, Jammu, Jammu & Kashmir, India
[3] Cent Univ Kashmir, Dept Biotechnol, Ganderbal, Jammu & Kashmir, India
[4] Univ Delhi, Dr BR Ambedkar Ctr Biomed Res, New Delhi, India
关键词
Cytotoxicity; Apoptosis; Therapeutic proteins; DRUG DEVELOPMENT; CYCLE CONTROL; BCL-2; FAMILY; IN-VITRO; DEATH; GLYCOPROTEIN; INDUCTION; LECTIN; LIFE; PROLIFERATION;
D O I
10.1016/j.ijbiomac.2019.05.120
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Withania somnifera exhibits different pharmacological activities which mainly stem from its broad range of bioactive molecules. Majority of these bioactive molecules, fall into the groupings of alkaloids, steroidal lactones, phenolic compounds and glycoproteins. In this study, we evaluated a novel protein fraction, named here as WSPF, isolated from Withania somnifera roots for its cytotoxic properties against various human cancer cell lines. WSPF exhibited apoptotic activity for each cancer cell line tested, demonstrating significant activity against MDA-MB-231 human breast cancer cells with an IC50 value of 92 mu g/mL WSPF induced mitochondrial-mediated apoptosis of MDA-MB-231 cells via extensive reactive oxygen species generation, dysregulation of Bax/Bcl-2, loss of mitochondria) membrane potential and caspase-3 activation. Additionally, we observed G2/M-phase cell cycle arrest, cleavage of nuclear lamin A/C proteins, and nuclear morphological changes. The present results highlight the anti-cancer properties of WSPF, indicating that the proteins in this fraction can be potential therapeutic agents for triple negative breast cancer treatment. (C) 2019 Published by Elsevier B.V.
引用
收藏
页码:77 / 87
页数:11
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