Paris Saponin VII Induces Apoptosis and Cell Cycle Arrest in Erythroleukemia Cells by a Mitochondrial Membrane Signaling Pathway

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Author(s): Xin Lin, Babu Gajendran, Krishnapriya M. Varier, Wuling Liu, Jingrui Song, Qing Rao, Chunlin Wang, Jianfei Qiu, Wei Ni, XuJie Qin, Min Wen, Haiyang Liu, Yanmei Li*

Journal Name: Anti-Cancer Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

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Background and Purpose: Leukemia considered a top-listed ailment, according to WHO, which contributes to the death of a major population of the world every year. Paris Saponin VII (PS), a saponin which was isolated from the roots of Trillium kamtschaticum, from our group, was reported to provide hemostatic, cytotoxic and antimicrobial activities. However, its molecular mechanism underlying the anti-proliferative effects remains unclear. Thus, this study hypothesized to assess that mechanism in PS treated HEL cells.

Methods: The MTT assay used to analyze the PS inhibited cell viability in the HEL cells. We further found that PS could induce S phase cell cycle arrest through flow cytometry as well as the western blot analysis of intrinsic and extrinsic apoptotic molecules.

Results: The MTT assay showed the IC50 concentration of PS as 0.667μM. The study revealed that PS treatment inhibits cell proliferation dose-dependently. It further caused mitochondrial membrane potential changes by PS treatment. Mechanistic protein expression revealed a dose-dependent upsurge for Bid and Bim molecules, while Bcl2 and PARP expression levels were significantly (P< 0.05) down-regulated in PS treated HEL cells resulting in caspase -3 release and increased the Bim levels upon 24h of incubation.

Conclusions: These findings indicate that PS possesses an excellent anti-leukemic activity via regulation of the mitochondrial pathway, leading to S phase cell cycle arrest and caspase-dependent apoptosis suggesting it as a potential alternative chemotherapeutic agent for leukemia patients.

Keywords: Leukemia, paris saponin VII, HEL, cell cycle, apoptosis, membrane signaling pathway.

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(E-pub Ahead of Print)
DOI: 10.2174/1871520620666200615134039
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