Luteolin Synergistically Enhances Antitumor Activity of Oxaliplatin in Colorectal Carcinoma via AMPK Inhibition

Abstract

Luteolin is a naturally-occurring polyphenolic compound that is known to have antioxidative and antitumor activities in vitro. This study aimed to examine the in vivo anticancer efficacy of luteolin in conjunction with oxaliplatin treatment using a colorectal carcinoma xenograft mouse model. HCT116 human colorectal carcinoma cells were subcutaneously implanted into BALB/c nude mice, followed by the intraperitoneal administration of luteolin at a dose of 50 mg/kg body weight (BW)/day with or without oxaliplatin at a dose of 10 mg/kg BW/day three times per week for a total of 3 weeks. The combined luteolin and oxaliplatin treatment resulted in the synergistic suppression of the growth of HCT116 xenograft tumors when compared to treatment with luteolin or oxaliplatin alone. In addition, the combined treatment significantly increased the expression of cleaved PARP and p53 in the xenograft tumors compared with the vehicle control, but only marginally affected the level of heme oxygenase-1 (HO-1). These results indicated that luteolin treatment retarded oxaliplatin-induced tumor growth by facilitating apoptotic cell death and inhibiting HO-1-mediated cytoprotection. Therefore, these findings suggest the synergistic potential of dietary luteolin in conjunction with conventional chemotherapy for the treatment of colorectal cancer.