title: Baicalein increases the cytotoxicity of cisplatin by enhancing gap junction intercellular communication.
abstract: Drug resistance limits the clinical application of cisplatin, a widely used chemotherapeutic agent. Gap junction (GJ) is a channel that enhances cytotoxicity of certain chemotherapeutic agents. Baicalein is well known for its antitumor activity. This study investigated the effect of baicalein on cisplatin cytotoxicity and the relationship between this effect and the modulation of the GJ function in connexin 26 (Cx26)‑transfected HeLa cells. The sulforhodamine B (SRB) assay was used to examine the effect of baicalein on cell viability. A 'parachute' assay was used to investigate the effect of baicalein on GJ function. The effects of baicalein on cisplatin cytotoxicity and GJ function were assayed by standard colony‑forming assays. The expression of Cx26 was monitored by western blotting. It was observed that exposure of Cx26‑transfected cells to cisplatin reduced the number of colonies formed in low‑density cultures (no GJ formation) and in high‑density cultures (GJ formation), but the toxic effect was greater when cells were seeded at a high density. In the absence of connexin expression or with blockage of connexin channels however, cell density had no effect on cisplatin toxicity. Baicalein significantly enhanced cisplatin cytotoxicity, but this effect required the presence of functional GJs between the cells. In conclusion, the dependence of cisplatin toxicity on cell density is mediated by GJs. Baicalein increases cisplatin cytotoxicity through enhancing GJ intercellular communication.
authors.affiliation: Department of Pharmacy, Sun Yat‑Sen Memorial Hospital, Sun Yat‑Sen University, Guangzhou, Guangdong 510120, P.R. China.
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Zhongshan School of Medicine, Sun Yat‑Sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Zhongshan School of Medicine, Sun Yat‑Sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Suzhi
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Zhongshan School of Medicine, Sun Yat‑Sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Zhongshan School of Medicine, Sun Yat‑Sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Tao
mesh_terms: D000970:Antineoplastic Agents / Q000633:toxicity*; D002450:Cell Communication / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity*; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics / Q000378:metabolism; D044950:Flavanones / Q000494:pharmacology*; D017629:Gap Junctions / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans
chemical_list: D000970:Antineoplastic Agents; D017630:Connexins; D044950:Flavanones; C000607042:GJB2 protein, human; D000072259:Connexin 26; C006680:baicalein; D002945:Cisplatin