Title :
P-Glycoprotein Is Not Involved in Pathway of Fas-Induced Apoptosis
Author :
Ling, Chun-hua ; Zheng, Shi-Ying ; Jiang, Dong ; Ge, Jin-Feng
Author_Institution :
Dept. of Med., First Affiliated Hosp. of Suzhou Univ., Suzhou, China
Abstract :
We verify whether P-glycoprotein (P-gp) could induce cell resistance to apoptosis by inhibiting caspase-8 and caspase-3. Human KB cells, either drug-sensitive or with multidrug resistance (MDR) phenotype caused by Over- expression of P-gp (KBv200 cells), were treated with anti-Fas (CH-11) to induce apoptosis. Cytotoxicity was detected by MTT assay. Symptoms of cell death were assessed by morphological observation after Hoechst33258 staining, activation of caspase-8 and caspase-3 was measured by Western blotting.Compared with KB cells, the resistance of KBv200 cells to VCR (vincristine) was about 51-fold higher.Anti-Fas (CH-11) induced cytotoxicity and apoptosis in both sensitive KB cells and MDR phenotype KBv200 cells. The IC50 of CH-11 in KB cells was similar to that in KBv200 cells. CH-11 induced similar apoptotic rates in both KB cells and KBv200 cells, which could be classified as caspase-dependent apoptotic pathway. Verapamil (VRP) did not affect CH-11-mediated apoptosis in KBv200 cells. Expression of P-glycoprotein does not induce resistance to caspase-8 and -3 activation or anti-Fas-induced cell apoptosis.
Keywords :
biochemistry; cellular biophysics; drugs; molecular biophysics; proteins; CH-11; Fas-induced apoptosis; Hoechst33258 staining; KBv200 cells; P-glycoprotein; P-gp overexpression; caspase-3; caspase-8; cell resistance; drug-sensitive phenotype; human KB cells; multidrug resistance phenotype; verapamil; Biomembranes; Birth disorders; Cardiology; Cells (biology); Drugs; Hospitals; Immune system; Surgery; Telephony; Video recording;
Conference_Titel :
Bioinformatics and Biomedical Engineering (iCBBE), 2010 4th International Conference on
Conference_Location :
Chengdu
Print_ISBN :
978-1-4244-4712-1
Electronic_ISBN :
2151-7614
DOI :
10.1109/ICBBE.2010.5515896