Gamma-linolenic acid modulates the response of multidrug-resistant K562 leukemic cells to anticancer drugs.
Gamma-linolenic acid (GLA) is known to have selective tumoricidal action. It is also reported that GLA may increase the cytotoxic activity of cancer chemotherapeutic agents in some cancer cells. The present study examined whether GLA pretreatment could modulate the response of multidrug-resistant K562/ADM leukemic cells to anticancer drugs. The cell viability assay results showed that GLA at 10 microg/ml enhanced cell growth inhibition induced by the MDR-type drugs doxorubicin, etoposide and vincristine, but could not enhance or even attenuated cell growth inhibition induced by the non-MDR-type drug cisplatin, mitomycin and fluorouracil in K562/ADM cells. Further flow cytometry results showed that GLA decreased the expression of P-glycoprotein, enhanced the accumulation of doxorubicin and rhodamine 123 in K562/ADM cells and inhibited the efflux of rhodamine 123 from K562/ADM cells, lowered the efflux rate. These results suggest that GLA could modulate the response to anti-cancer agents in P-gp overexpressing multidrug-resistant cells, and the mechanism may be by decreasing the P-gp expression and inhibiting P-gp function.
Kong
Xiuqin
X
Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing 210046, PR China.
Ge
Haitao
H
Chen
Li
L
Liu
Zhili
Z
Yin
Zhimin
Z
Li
Ping
P
Li
Mei
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis / Q000502:physiology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D020014:K562 Cells; D017965:gamma-Linolenic Acid / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D017965:gamma-Linolenic Acid