Protopanaxadiol(PPD)is considered to be the most active pharmacological element in ginseng and has been widely studied for its anticancer effects.However,the detailed anticancer mechanism of this compound in cervical ...Protopanaxadiol(PPD)is considered to be the most active pharmacological element in ginseng and has been widely studied for its anticancer effects.However,the detailed anticancer mechanism of this compound in cervical cancer(CC)HeLa cells has yet to be thoroughly understood.In this research,we discovered that PPD effectively inhibits CC HeLa cell proliferation and cause morphological changes,with an IC50 measured at 34.18μM.Based on mRNA-seq analysis,we revealed the mechanism by which PPD inhibits HeLa cell proliferation.The results from Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated significant enrichment of DGEs in the cell cycle and protein processing in the endoplasmic reticulum(PPER)pathway.By inducing DNA damage,PPD resulted in G0/G1 phase cell cycle arrest,inhibited Bcl-2 to cause ROS production,upregulated cytochrome c(Cyto-c)expression,thereby further reducing mitochondrial membrane potential(Δψm),activated the caspase family,and induced cell apoptosis.In addition,PPD promoted Ca^(2+)leakage,downregulated the PPER pathway(PERK,ATF6,and IRE1α),increased Chop expression levels,and mediated programmed cell death.These observations imply that PPD can induce apoptosis in HeLa cells,highlighting its potential as a novel natural therapeutic for cervical cancer.展开更多
基金supported by the National Key Research&Development Program of China(2022YFF1100305)the Juan de la Cierva Incorporación for Hui Cao(IJC2020-046055-I).
文摘Protopanaxadiol(PPD)is considered to be the most active pharmacological element in ginseng and has been widely studied for its anticancer effects.However,the detailed anticancer mechanism of this compound in cervical cancer(CC)HeLa cells has yet to be thoroughly understood.In this research,we discovered that PPD effectively inhibits CC HeLa cell proliferation and cause morphological changes,with an IC50 measured at 34.18μM.Based on mRNA-seq analysis,we revealed the mechanism by which PPD inhibits HeLa cell proliferation.The results from Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated significant enrichment of DGEs in the cell cycle and protein processing in the endoplasmic reticulum(PPER)pathway.By inducing DNA damage,PPD resulted in G0/G1 phase cell cycle arrest,inhibited Bcl-2 to cause ROS production,upregulated cytochrome c(Cyto-c)expression,thereby further reducing mitochondrial membrane potential(Δψm),activated the caspase family,and induced cell apoptosis.In addition,PPD promoted Ca^(2+)leakage,downregulated the PPER pathway(PERK,ATF6,and IRE1α),increased Chop expression levels,and mediated programmed cell death.These observations imply that PPD can induce apoptosis in HeLa cells,highlighting its potential as a novel natural therapeutic for cervical cancer.
