Abstract

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).

Abbreviation

ANOVA, Analysis of variance; BSA, bovine serum albumin; CREB, cAMP-response-element binding; DMEM, Dulbecco's modified Eagle's medium; ECL, enhanced chemiluminesence; EGFR, epidermal growth factor receptor; ELISA, enzyme-linked immunosorbent assay; ERK, extracellular signal-related kinase; FBS, fetal bovine serum; MAPK, mitogen-activated protein kinase; PBS, phosphate-buffered saline; PI, propidium iodide; PMS, phenazine methosulfate; VEGF, vascular endothelial growth factor.