NDLI: A novel curcumin-like dienone induces apoptosis in triple-negative breast cancer cells

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Cellular Oncology : Volume 39, Issue 2, April 2016

Cellular Oncology : Volume 39, Issue 1, February 2016

Cellular Oncology : Volume 38

Cellular Oncology : Volume 37

Cellular Oncology : Volume 36

Cellular Oncology : Volume 35

Cellular Oncology : Volume 34

A novel curcumin-like dienone induces apoptosis in triple-negative breast cancer cells

Content Provider	Springer Nature Link
Author	Robles Escajeda, Elisa Das, Umashankar Ortega, Nora M. Parra, Karla Francia, Giulio Dimmock, Jonathan R. Varela Ramirez, Armando Aguilera, Renato J.
Copyright Year	2016
Abstract	According to the World Health Organization (WHO), breast cancer is the most common cancer affecting women worldwide. In the USA ~12.3 % of all women are expected to be diagnosed with various types of breast cancer, exhibiting varying degrees of therapeutic response rates. Therefore, the identification of novel anti-breast cancer drugs is of paramount importance.The 1,5-diaryl-3-oxo-1,4-pentadienyl pharmacophore was incorporated into a number of cytotoxins. Three of the resulting dienones, 2a, 2b and 2c, were tested for their anti-neoplastic potencies in a variety of human breast cancer-derived cell lines, including the triple negative MDA-MB-231 cell line and its metastatic variant, using a live-cell bio-imaging method. Special emphasis was put on dienone 2c, since its anti-cancer activity and its mode of inflicting cell death have so far not been reported.We found that all three dienones exhibited potent cytotoxicities towards the breast cancer-derived cell lines tested, whereas significantly lower toxicities were observed towards the non-cancerous human breast cell line MCF-10A. The dienones 2b and 2c exhibited the greatest selective cytotoxicity at submicromolar concentration levels. We found that these two dienones induced phosphatidylserine externalization in MDA-MB-231 cells in a concentration-dependent manner, suggesting that their cytotoxic effect might be mediated by apoptosis. This possibility was confirmed by our observation that the dienone 2c can induce mitochondrial depolarization, caspase-3 activation, cell cycle disruption and DNA fragmentation in MDA-MB-231 cells.Our findings indicate that dienone 2c uses the mitochondrial/intrinsic pathway to inflict apoptosis in triple negative MDA-MB-231 breast cancer-derived cells. This observation warrants further assessment of dienone 2c as a potential anti-breast cancer drug.
Starting Page	265
Ending Page	277
Page Count	13
File Format	PDF
ISSN	22113428
Journal	Cellular Oncology
Volume Number	39
Issue Number	3
e-ISSN	22113436
Language	English
Publisher	Springer Netherlands
Publisher Date	2016-02-26
Publisher Institution	International Society for Cellular Oncology
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Anti-cancer drug discovery Apoptosis Caspase-3 Cell cycle DNA fragmentation Mitochondrial depolarization Curcumin analogues Cancer Research Biomedicine general Pathology Oncology
Content Type	Text
Resource Type	Article
Subject	Cancer Research Molecular Medicine Oncology

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