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姜黄素衍生物1,2-双[(3E,5E)-3,5-双[(2-氯苯基)亚甲基]-4-氧代-1-哌啶基]乙烷-1,2-二酮(ST03)诱导卵巢癌细胞中线粒体介导的凋亡,并抑制EAC小鼠模型中的肿瘤进展。

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.

作者信息

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

机构信息

Institute of Bioinformatics and Applied Biotechnology, Electronic city phase 1, Bangalore 560100, Karnataka, India; Manipal Academy of Higher Education, Manipal 576104, India.

Institute of Bioinformatics and Applied Biotechnology, Electronic city phase 1, Bangalore 560100, Karnataka, India.

出版信息

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

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.

摘要

姜黄素以其抗癌特性而闻名,但其临床应用因生物利用度差和化学稳定性低而受到限制。在本研究中,我们报告了姜黄素衍生物ST03(1,2 - 双[(3E,5E)-3,5 - 双[(2 - 氯苯基)亚甲基]-4 - 氧代-1 - 哌啶基]乙烷-1,2 - 二酮)与姜黄素相比具有约14倍更好的生物利用度,并且在血浆中可检测长达12小时。ST03诱导活性氧(ROS),激活内在凋亡途径,这在卵巢癌细胞系PA1和A2780中表现为线粒体膜电位的破坏以及促凋亡蛋白的诱导。ST03还阻断了卵巢癌细胞的迁移。ST03通过激活内在凋亡途径在EAC小鼠模型中发挥体内抗肿瘤作用。我们的研究结果表明,姜黄素衍生物ST03具有更好的生物利用度和稳定性,且在体内无明显毒性,是一种有前景的抗癌治疗候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7380/8607274/e0e133acf01c/ga1.jpg

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