title: Panax notoginseng saponins enhances the cytotoxicity of cisplatin via increasing gap junction intercellular communication.
abstract: Panax Notoginseng Saponins (PNS) have been well known to have anti-tumor activity and enhance cytotoxicity of some cancer chemotherapy agents, but the mechanisms underlying these effects are still unknown. This study investigates the effect of PNS on cytotoxicity of cisplatin and the relationship between this effect and the modulation of gap junctions (GJ) function by PNS in a transfected cell line. The cytotoxicity of cisplatin (0.25-1 µg/mL) was increased in the presence of GJ. Inhibition of gap junction by either GJ blocker or interception of Connexin (Cx) expression decreased the cytotoxicity of cisplatin. Increasing GJ function enhanced cytotoxicity of cisplatin, only in the cells with functional GJ. PNS (50-200 µg/mL) significantly enhanced cisplatin cytotoxicity, but this effect required functional gap junctions between the cells. Exposure of the cells to PNS (50-200 µg/mL) for 4 h leads to a significant enhance in dye coupling of GJ in a dose-dependent manner. These results suggest that PNS increases the cytotoxicity of cisplatin through enhancement of GJ activity.
authors.affiliation: Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, P. R. China.
authors.forename: Mei-ling
authors.initials: ML
authors.lastname: Yu
authors.forename: Cui-ling
authors.initials: CL
authors.lastname: Zhang
authors.forename: Dong-dong
authors.initials: DD
authors.lastname: Yuan
authors.forename: Xu-hui
authors.initials: XH
authors.lastname: Tong
authors.forename: Liang
authors.initials: L
authors.lastname: Tao
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols; D002450:Cell Communication / Q000187:drug effects* / Q000502:physiology; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use*; D017630:Connexins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D017629:Gap Junctions / Q000187:drug effects* / Q000502:physiology; D006367:HeLa Cells; D041743:Herb-Drug Interactions; D006801:Humans; D053723:Panax notoginseng / Q000737:chemistry*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D012503:Saponins / Q000494:pharmacology / Q000627:therapeutic use*; D014162:Transfection; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000503:physiopathology*
chemical_list: D000970:Antineoplastic Agents; D017630:Connexins; D010936:Plant Extracts; D012503:Saponins; D002945:Cisplatin