Curcumin derivative 1, 2-bis [(3E, 5E)-3, 5-bis [(2-chlorophenyl) methylene]-4-oxo-1-piperidyl] ethane-1, 2-dione (ST03) induces mitochondria mediated apoptosis in ovarian cancer cells and inhibits tumor progression in EAC mouse model

Jinsha Koroth; Raghunandan Mahadeva; Febina Ravindran; Tanvi R Parashar; Vinay Teja; Subhas S Karki; Bibha Choudhary

doi:10.1016/j.tranon.2021.101280

Curcumin derivative 1, 2-bis [(3E, 5E)-3, 5-bis [(2-chlorophenyl) methylene]-4-oxo-1-piperidyl] ethane-1, 2-dione (ST03) induces mitochondria mediated apoptosis in ovarian cancer cells and inhibits tumor progression in EAC mouse model

Transl Oncol. 2022 Jan;15(1):101280. doi: 10.1016/j.tranon.2021.101280. Epub 2021 Nov 19.

Authors

Jinsha Koroth¹, Raghunandan Mahadeva², Febina Ravindran², Tanvi R Parashar², Vinay Teja², Subhas S Karki³, Bibha Choudhary⁴

Affiliations

¹ Institute of Bioinformatics and Applied Biotechnology, Electronic city phase 1, Bangalore 560100, Karnataka, India; Manipal Academy of Higher Education, Manipal 576104, India.
² Institute of Bioinformatics and Applied Biotechnology, Electronic city phase 1, Bangalore 560100, Karnataka, India.
³ Department of Pharmaceutical Chemistry, KLE Academy of Higher Education and Research, KLE College of Pharmacy, Rajajinagar, Bangalore, KN, India.
⁴ Institute of Bioinformatics and Applied Biotechnology, Electronic city phase 1, Bangalore 560100, Karnataka, India. Electronic address: vibha@ibab.ac.in.

Abstract

Curcumin is known for its anticancer properties, but its clinical application is limited due to its poor bioavailability and chemical stability. In this study we report the curcumin derivative, ST03 (1,2-bis[(3E,5E)-3,5-bis[(2-chlorophenyl)methylene]-4-oxo-1-piperidyl]ethane-1,2-dione) exhibits ∼ 14 fold better bioavailability compared to curcumin and is detectable in plasma up to 12 h. ST03 induces ROS, activates the intrinsic apoptotic pathway as evident by disruption of mitochondrial membrane potential, and induction of proapoptotic proteins in ovarian cancer lines PA1 and A2780. ST03 also blocked the migration of ovarian cancer cells. ST03 exerted its antitumor effect in-vivo in the EAC mouse model by activating the intrinsic apoptotic pathway. Our findings demonstrate ST03, a curcumin derivative, with better bioavailability and stability with no discernable toxicity in vivo to be a promising drug candidate for anticancer therapies.

Keywords: Apoptosis; Bioavailability; Curcumin derivative; Ovarian cancer; ST03.