Honokiol augments the anti-cancer effects of oxaliplatin on colon cancer cell: Apoptosis and analysis of the molecular mechanisms

The drug oxaliplatin is important in the chemotherapy of colorectal carcinoma, but its toxicity, especially dose-related neurosensory toxicity, is not well tolerated. We investigated if honokiol could augment the anti-tumor effect of oxaliplatin in colon cancer HT-29 cells in vitro and determined if honokiol could be used with oxaliplatin to decrease its dose. Cell proliferation, apoptosis, and prostaglandin E2 (PGE2) and vascular endothelial growth factor (VEGF) levels were investigated. Expression of cyclo-oxygenase 2 (COX-2), VEGF, AKT/p-AKT, extracellular signal-related kinase (ERK)1/2/p-ERK1/2, nuclear factor kappa B (NF-κB), P65/p-P65, and caspase-3 was examined. Honokiol or oxaliplatin alone suppressed the proliferation of HT-29 cells in a concentration-dependent manner. HT-29 cells were more sensitive to oxaliplatin treatment in the presence of honokiol. Oxaliplatin combined with honokiol improved the rate of HT-29 cell apoptosis and reduced PGE2 and VEGF secretion levels. Expression of COX-2 and VEGF protein and phosphorylation of AKT, ERK1/2, NF-κB and P65 were also inhibited, caspase-3 levels were upregulated after honokiol treatment. Therefore, honokiol can be combined with oxaliplatin in the chemotherapy of colorectal carcinoma, this combination allows a reduction in oxaliplatin dose, and thereby reduces its adverse effects, and may also enhance the chemotherapeutic effect of oxaliplatin for this disease.   Key words: Honokiol, colorectal cancer, apoptosis, oxaliplatin, nuclear factor-kappa B (NF-κB).