Abstract
The anti-apoptotic BCL2 family of proteins elicits a broad cell survival program mainly by promoting cell migration, invasion, and metastasis. High expression level of BCL2 family proteins is a characteristic feature of cancer cells, especially in cisplatin-resistant cancer cells. Recent studies have shown that BCL2 family proteins play a housekeeping role in modulating mitochondrial dynamics. However, it is not clear whether BCL2 family proteins are relevant to mitochondrial fission and fusion in cisplatin-resistant ovarian cancer cells. Here, we report that the BCL2/BCLXL inhibitor ABT737 induced apoptosis more potently in cisplatin-resistant SKOV3/DDP ovarian cancer cells than in cisplatin-sensitive SKOV3 ovarian cancer cells. ABT737 significantly increased levels of DRP1 in mitochondria and increased rates of mitochondrial fission, and then induced cytochrome C release from mitochondria and mitophagy in SKOV3/DDP cells. Mdivi-1, a selective inhibitor of DRP1, weakened ABT737-induced mitochondrial fission, intrinsic apoptotic pathways, and mitophagy in SKOV3/DDP cells. Taken together, these results demonstrate a novel function of ABT737 in inducing DRP1-dependent apoptotic mitochondrial fission and highlight that targeting anti-apoptotic BCL2 family proteins may be an emerging therapeutic strategy for patients with cisplatin-resistant ovarian cancer.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
