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.

Flavonoid Components, Distribution, and Biological Activities in Taxus: A review

“…Apigenin 1 had a synergistic effect along with paclitaxel in cervical carcinoma (HeLa) cells, leading to 29% decrease of cell viability and 24% improvement of cell apoptosis with the combination index of 0.3918 ± 0.0436 [ 105 ]. Similarly, there was a synergistic inhibitory effect on human colorectal carcinoma resulting from luteolin 2 and oxaliplatin [ 10 ].…”

Quercetin-Induced Glutathione Depletion Sensitizes Colorectal Cancer Cells to Oxaliplatin

“…To evaluate cell viability, HCT116 cells were seeded in a 96-well plate (SPL Life Sciences co., Ltd.) at a density of 5 × 10 3 cells per well. Following treatment with QUE in the absence or presence of OXP for 3 or 6 days, the medium was removed and CCK solution (D-Plus TM CCK cell viability assay kit, Dongin Biotech., Seoul, Republic of Korea) was added to each well [ 21 , 22 ]. The plate was incubated in the cell culture incubator for 1 h. The absorbance at 450 nm was detected using a microplate reader (Sunrise TM , Tecan Group Ltd., Männedorf, Switzerland).…”

Luteolin, a Potent Anticancer Compound: From Chemistry to Cellular Interactions and Synergetic Perspectives

“…Similarly, the administration of luteolin and 5-FU demonstrated apoptosis induction via increased levels of p53, p21, and caspase 3 in the solid Ehrlich carcinoma mice model [ 100 ]. Additionally, the combined treatment of luteolin and oxaliplatin significantly increased apoptosis in the colorectal carcinoma xenograft-mouse model by elevating the expression of cleaved PARP and p53 via inhibition of the AMPK pathway [ 101 ]. Administration of polyphenols such as (-)-epigallocatechin-3-gallate with luteolin has been observed to synergistically inhibit TGF-β through RhoA and ERK inhibition pathways, and to decrease the serum levels of HGF and VEGF in prostate cancer cells [ 102 ].…”