The comparison analysis of polyphyllin I and its analogues induced apoptosis of colon and lung cancer cells via mitochondrial dysfunction

Autor:	Ya-Di Zhu, Gui-Lin Wei, Ming Lei, Dan-Dan Wang, Xiao-Fang Yang, Huan Geng, Lijiao You, Guang-Bo Ge
Rok vydání:	2021
Předmět:	Lung Neoplasms Apoptosis Diosgenin Pharmacology Toxicology 030226 pharmacology & pharmacy Inhibitory Concentration 50 03 medical and health sciences 0302 clinical medicine medicine Humans Cytotoxic T cell Inner mitochondrial membrane Lung cancer Cytotoxicity Membrane Potential Mitochondrial Dose-Response Relationship Drug Chemistry General Medicine Polyphyllin VII Saponins medicine.disease Mitochondria A549 Cells Cell culture Colonic Neoplasms Steroids Drug Screening Assays Antitumor Reactive Oxygen Species HT29 Cells 030217 neurology & neurosurgery Polyphyllin I Signal Transduction
Zdroj:	Basic & Clinical Pharmacology & Toxicology. 129:15-25
ISSN:	1742-7843 1742-7835
Popis:	Polyphyllin I (PPI) and its analogues, including polyphyllin II (PPII), polyphyllin VI (PPVI) and polyphyllin VII (PPVII), are major bioactive compounds isolated from the Chinese herb Chonglou. However, the susceptibilities of PPI and its analogues towards the different cell lines are diversified and the mechanisms are not fully clarified. Thus, the present study aimed to investigate the cytotoxicity of PPI and its analogues on two different cell lines, as well as to explore the underlying mechanisms of these agents via inducing mitochondrial dysfunction. The results showed that PPI and its analogues were cytotoxic agents towards both A549 and HT-29 cells, with IC50 values ranged from 1.0 to 4.5 μmol/L. Further investigations demonstrated that they decreased the mitochondrial membrane potentials of both A549 and HT-29 cells in a dose-dependent manner. Among all tested compounds, PPVI and PPI induced the most obvious changes in Ca2+ haemostasis in these two cell lines. In addition, they could induce the accumulation of ROS in cells and down-regulated the Bcl-2 expression, up-regulated the Bax expression and induced the activity of cleaved caspase-3 in cells. Collectively, our findings clearly demonstrated the cytotoxic differences and mechanisms of PPI and its analogues induced cell apoptosis and could partially explain the anticancer effects of these natural constituents in Chonglou.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f41ea77f0851248a584d882bf058761d https://doi.org/10.1111/bcpt.13596 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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