title: Suppressive effect of tobacco smoke extracts on oral P-glycoprotein function and its impact in smoke-induced insult to oral epidermal cells.
abstract: P-glycoprotein (Pgp) participates in the export of numerous toxins, drugs, and physiological compounds. To examine the involvement of Pgp in smoke-induced oral cell insult, the effects of extracts of the mainstream tobacco smoke (TS) on Pgp were studied in an oral epidermal carcinoma cell line, OECM-1. TS was first extracted with cyclohexane (CTS) and the residues were further extracted with isopropanol (ITS). For comparison, cells were exposed to CTS and ITS at the concentrations according to their relative extraction yield. ITS but not CTS decreased the efflux of a Pgp substrate, rhodamine (Rh) 123, in a concentration- and time-dependent manner. The efflux was also decreased by co-exposure to CTS and ITS. However, immunoblot analysis revealed that the protein level of Pgp was not affected by ITS. Naphthalene, mainly detected in the ITS, decreased Rh 123 efflux. However, the efflux activity was not affected by benzo(a)pyrene and nicotine, which were present in the CTS and both extracts, respectively. Co-exposure to CTS in combination with ITS, naphthalene, or verapamil enhanced cell insult compared to single exposure. These results demonstrated that smoke and its constituent, naphthalene, diminished Pgp-mediated efflux. The reduction in Pgp function could be a stimulatory factor of TS-induced oral cell insult.
authors.affiliation: National Research Institute of Chinese Medicine, Taipei, Taiwan, ROC.
authors.forename: Wen-Chi
authors.initials: WC
authors.lastname: Pan
authors.forename: Ruei-Ming
authors.initials: RM
authors.lastname: Chen
authors.forename: Yuh-Chiang
authors.initials: YC
authors.lastname: Shen
authors.forename: Chien-Chih
authors.initials: CC
authors.lastname: Chen
authors.forename: Yune-Fang
authors.initials: YF
authors.lastname: Ueng
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism / Q000502:physiology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004817:Epidermis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D015151:Immunoblotting; D009061:Mouth Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012906:Smoke / Q000032:analysis; D013997:Time Factors
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D012906:Smoke