Therapeutic potential of Bcl-xL /Mcl-1 synthetic inhibitor JY-1-106 and retinoids for human triple-negative breast cancer treatment

Oncology Letters
Mariarita PerriMaureen A Kane

Abstract

Overexpression of anti-apoptotic proteins belonging to the B cell lymphoma (Bcl)-2 family is observed in numerous cancer types and has been postulated to promote cancer cell survival and chemotherapy resistance. Bcl-extra large (xL)/myeloid cell leukemia sequence (Mcl)-1 was demonstrated to be expressed at relatively high levels in clinically aggressive basal-like cancers and inhibiting Bcl-xL overexpression could potentially provoke cell death. A molecule able to target Bcl-xL/Mcl-1, JY-1-106, is herein under investigation. It is also known that vitamin A-derived compounds exhibit antitumor activity in a variety of in vitro experimental models, promoting their effects via nuclear receptor isoforms including retinoic acid receptors (RARs). Pre-clinical observation highlighted that triple negative (estrogen receptor/progesterone receptor/human epidermal growth factor receptor)-breast cancer cells displayed resistance to retinoids due to the RARγ high expression profile. The present study used the triple-negative human breast cancer cell line, MDA-MB-231, to analyze the effects of the Bcl-xL/Mcl-1 synthetic inhibitor, JY-1-106, alone or in combination with retinoids on cell viability. The results revealed a synergistic effect in ...Continue Reading

Citations

Feb 27, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Alessia FazioErika Cione
Mar 28, 2019·Frontiers in Molecular Biosciences·Mariarita PerriMaria Cristina Caroleo
Jun 21, 2020·Anti-cancer Agents in Medicinal Chemistry·Milad AshrafizadehAmirhossein Sahebkar

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