PMID- 16038636 OWN - NLM STAT- MEDLINE DCOM- 20060503 LR - 20181201 IS - 1671-4083 (Print) IS - 1671-4083 (Linking) VI - 26 IP - 8 DP - 2005 Aug TI - Effect of curcumin on multidrug resistance in resistant human gastric carcinoma cell line SGC7901/VCR. PG - 1009-16 AB - AIM: To investigate the reversal effects of curcumin on multidrug resistance (MDR) in a resistant human gastric carcinoma cell line. METHODS: The cytotoxic effect of vincristine (VCR) was evaluated by MTT assay. The cell apoptosis induced by VCR was determined by propidium iodide (PI)-stained flow cytometry (FCM) and a morphological assay using acridine orange (AO)/ethidium bromide (EB) dual staining. P-glycoprotein (P-gp) function was demonstrated by the accumulation and efflux of rhodamine123 (Rh123) using FCM. The expression of P-gp and the activation of caspase-3 were measured by FCM using fluorescein isothiocyanate (FITC)-conjugated anti-P-gp and anti-cleaved caspase-3 antibodies, respectively. RESULTS: Curcumin, at concentrations of 5 micromol/L, 10 micromol/L, or 20 micromol/L, had no cytotoxic effect on a parent human gastric carcinoma cell line (SGC7901) or its VCR-resistant variant cell line (SGC7901/VCR). The VCR-IC50 value of the SGC7901/VCR cells was 45 times more than that of the SGC7901cells and the SGC7901/VCR cells showed apoptotic resistance to VCR. SGC7901/VCR cells treated with 5 micromol/L, 10 micromol/L, or 20 micromol/L curcumin decreased the IC50 value of VCR and promoted VCR-mediated apoptosis in a dose-dependent manner. Curcumin (10 micromol/L) increased Rh123 accumulation and inhibited the efflux of Rh123 in SGC7901/VCR cells, but did not change the accumulation and efflux of Rh123 in SGC7901 cells. P-gp was overexpressed in SGC7901/VCR cells, whereas it was downregulated after a 24-h treatment with curcumin (10 micromol/L). Resistant cells treated with 1 mumol/L VCR alone showed 77% lower levels of caspase-3 activation relative to SGC7901 cells, but the activation of caspase-3 in the resistant cell line increased by 44% when cells were treated with VCR in combination with curcumin. CONCLUSION: Curcumin can reverse the MDR of the human gastric carcinoma SGC7901/VCR cell line. This might be associated with decreased P-gp function and expression, and the promotion of caspase-3 activation in MDR cells. FAU - Tang, Xiao-qing AU - Tang XQ AD - Department of Physiology, Nanhua University, Hengyang 421001, China. FAU - Bi, Hu AU - Bi H FAU - Feng, Jian-qiang AU - Feng JQ FAU - Cao, Jian-guo AU - Cao JG LA - eng PT - Comparative Study PT - Journal Article PL - United States TA - Acta Pharmacol Sin JT - Acta pharmacologica Sinica JID - 100956087 RN - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 1) RN - 0 (Antineoplastic Agents) RN - 1N3CZ14C5O (Rhodamine 123) RN - 5J49Q6B70F (Vincristine) RN - EC 3.4.22.- (CASP3 protein, human) RN - EC 3.4.22.- (Caspase 3) RN - EC 3.4.22.- (Caspases) RN - IT942ZTH98 (Curcumin) SB - IM MH - ATP Binding Cassette Transporter, Subfamily B, Member 1/biosynthesis/physiology MH - Antineoplastic Agents/pharmacology MH - Caspase 3 MH - Caspases/metabolism MH - Cell Line, Tumor MH - Cell Proliferation/*drug effects MH - Cell Survival/drug effects MH - Curcumin/*pharmacology MH - Dose-Response Relationship, Drug MH - Drug Resistance, Multiple/*drug effects MH - Drug Resistance, Neoplasm/drug effects MH - Enzyme Activation/drug effects MH - Flow Cytometry MH - Humans MH - Inhibitory Concentration 50 MH - Rhodamine 123/pharmacokinetics MH - Stomach Neoplasms/metabolism/pathology MH - Vincristine/*pharmacology EDAT- 2005/07/26 09:00 MHDA- 2006/05/04 09:00 CRDT- 2005/07/26 09:00 PHST- 2005/07/26 09:00 [pubmed] PHST- 2006/05/04 09:00 [medline] PHST- 2005/07/26 09:00 [entrez] AID - 10.1111/j.1745-7254.2005.00149.x [doi] PST - ppublish SO - Acta Pharmacol Sin. 2005 Aug;26(8):1009-16. doi: 10.1111/j.1745-7254.2005.00149.x.