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

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* and Yanmei Li*   Pages 498 - 507 ( 10 )

Abstract:

<P>Background and Purpose: Leukemia is 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. </P><P> Methods: The MTT assay was 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. </P><P> 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. </P><P> Conclusion: These findings indicate that PS possesses an excellent anti-leukemic activity via the 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.</P>

Keywords:

Leukemia, Paris Saponin VII, HEL, cell cycle, apoptosis, membrane signaling pathway.

Affiliation:

State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, Guizhou Province- 550014, State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, Guizhou Province- 550014, Department of Medical Biochemistry, Dr. ALM PGIBMS, University of Madras, Taramani Campus, Chennai, Tamilnadu-600113, State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, Guizhou Province- 550014, State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, Guizhou Province- 550014, State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, Guizhou Province- 550014, State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, Guizhou Province- 550014, State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, Guizhou Province- 550014, State Key Laboratory of Phytochemistry and Plant Resources in West China, and Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, State Key Laboratory of Phytochemistry and Plant Resources in West China, and Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, College of Basic Medicine, Guizhou Medical University, Guiyang, Guizhou, State Key Laboratory of Phytochemistry and Plant Resources in West China, and Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, Guizhou Province- 550014

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