TY - JOUR
T1 - Suppressive effect of tobacco smoke extracts on oral P-glycoprotein function and its impact in smoke-induced insult to oral epidermal cells
AU - Pan, Wen Chi
AU - Chen, Ruei Ming
AU - Shen, Yuh Chiang
AU - Chen, Chien Chih
AU - Ueng, Yune Fang
PY - 2009/3/10
Y1 - 2009/3/10
N2 - 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.
AB - 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.
KW - Oral cell insult
KW - P-glycoprotein
KW - Tobacco smoke
UR - http://www.scopus.com/inward/record.url?scp=59049086808&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=59049086808&partnerID=8YFLogxK
U2 - 10.1016/j.toxlet.2008.12.007
DO - 10.1016/j.toxlet.2008.12.007
M3 - Article
C2 - 19135510
AN - SCOPUS:59049086808
SN - 0378-4274
VL - 185
SP - 116
EP - 123
JO - Toxicology Letters
JF - Toxicology Letters
IS - 2
ER -