Effect of curcumin on multidrug resistance in resistant human gastric carcinoma cell line SGC7901/VCR.
OBJECTIVE
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.


CONCLUSIONS
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.
Tang
Xiao-qing
XQ
Department of Physiology, Nanhua University, Hengyang 421001, China.
Bi
Hu
H
Feng
Jian-qiang
JQ
Cao
Jian-guo
JG
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000502:physiology; D000970:Antineoplastic Agents / Q000494:pharmacology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D020128:Inhibitory Concentration 50; D020112:Rhodamine 123 / Q000493:pharmacokinetics; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology; D014750:Vincristine / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D020112:Rhodamine 123; D014750:Vincristine; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D003474:Curcumin