![conference banner](/images/conference-banner.jpeg)
Abstract
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.
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.
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.
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.
Keywords: Leukemia, Paris Saponin VII, HEL, cell cycle, apoptosis, membrane signaling pathway.
[PMID: 24784336]
[http://dx.doi.org/10.3322/caac.21208] [PMID: 24399786]
[http://dx.doi.org/10.1016/j.phytochem.2008.08.004] [PMID: 18822438]
[http://dx.doi.org/10.1016/j.phytochem.2016.09.006] [PMID: 27665149]
[http://dx.doi.org/10.1016/j.jconrel.2016.06.008] [PMID: 27282414]
[http://dx.doi.org/10.1039/C8TB02159G] [PMID: 32254933]
[http://dx.doi.org/10.3390/ijms19020448] [PMID: 29393886]
[http://dx.doi.org/10.1038/bjc.2015.85] [PMID: 25742467]
[http://dx.doi.org/10.1038/leu.2009.20 ] [PMID: 19282832]
[http://dx.doi.org/10.3109/13880209.2014.907323] [PMID: 25026337]
[http://dx.doi.org/10.1186/s12885-019-5914-8] [PMID: 31375085]
[http://dx.doi.org/10.1016/j.matlet.2014.02.003]
[http://dx.doi.org/10.1007/s12668-019-00645-9]
[http://dx.doi.org/10.1111/febs.14690] [PMID: 30387554]
[http://dx.doi.org/10.18632/oncotarget.14377] [PMID: 28052010]
[http://dx.doi.org/10.1016/S0928-4680(00)00053-5] [PMID: 10996508]
[http://dx.doi.org/10.1038/sj.cdd.4401610] [PMID: 15818400]
[http://dx.doi.org/10.1016/j.ejmech.2018.01.084] [PMID: 29438890]
[http://dx.doi.org/10.1186/2008-2231-22-3] [PMID: 24393601]
[http://dx.doi.org/10.1038/aps.2009.19] [PMID: 19270722]
[http://dx.doi.org/10.1016/j.canlet.2006.12.013] [PMID: 17223257]
[http://dx.doi.org/10.1111/j.1600-0609.2008.01116.x] [PMID: 18616510]
[PMID: 23484696]
[PMID: 24989284]
[http://dx.doi.org/10.1186/2047-783X-19-41] [PMID: 25128382]
[http://dx.doi.org/10.1016/j.jep.2019.111903] [PMID: 31047966]
[http://dx.doi.org/10.1002/ptr.6029] [PMID: 29377384]
[http://dx.doi.org/10.3389/fonc.2011.00023] [PMID: 22655234]
[http://dx.doi.org/10.1101/cshperspect.a006080] [PMID: 26626938]
[http://dx.doi.org/10.1016/j.febslet.2014.01.050] [PMID: 24530529]
[http://dx.doi.org/10.1038/cdd.2010.135] [PMID: 21072056]
[PMID: 24134011]
[http://dx.doi.org/10.1182/blood-2004-03-0868] [PMID: 15150082]
[http://dx.doi.org/10.1016/j.ejmech.2015.04.031] [PMID: 25899339]
[http://dx.doi.org/10.3892/ijo.2018.4349] [PMID: 29620258]
[http://dx.doi.org/10.1101/gad.1126903] [PMID: 14561771]
[http://dx.doi.org/10.1016/j.ejmech.2017.11.007] [PMID: 29133049]
[http://dx.doi.org/10.3109/10428194.2013.855307] [PMID: 24295132]
[http://dx.doi.org/10.1016/j.trsl.2018.07.013] [PMID: 30144423]
[http://dx.doi.org/10.3390/molecules22081299] [PMID: 28777347]
[http://dx.doi.org/10.1007/978-1-4419-6706-0_6]
[http://dx.doi.org/10.3892/or.10.5.1601] [PMID: 12883747]
[http://dx.doi.org/10.1039/C2FO30167A] [PMID: 23175101]
![Wayfinder Image](/images/wayfinder.jpg)