Inhibitory effect of Manuka honey on human colon cancer HCT-116 and LoVo cells growth. Part 1: Suppression of proliferation, promotion of apoptosis and arrest of cell cycle
Food & Function, Accepted Manuscript
Numerous investigations have been made on plant phenolic compounds and cancer prevention in recent decades. Manuka honey (MH) represents a good source of phenolic compounds such as luteolin, kaempferol, quercetin, gallic acid and syringic acid.
The aim of this work was to evaluate the chemopreventive effects of MH on human colon cancer HCT-116 and LoVo cells. Both cells were exposed to different concentration of MH (0-20 mg/mL for HCT-116 cells and 0-60 mg/mL for LoVo cells) for 48 h to measure apoptosis and cell cycle arrest as well as apoptosis and cell cycle regulatory gene and protein expression. MH exhibited profound inhibitory effects on cellular growth by reducing the proliferation ability, inducing apoptosis and arresting cell cycle in a dose-dependent manner.
Interestingly, MH treatment in non-malignant cells did not exert any significant toxicity at similar concentration. The apoptosis event was associated with increasing expression of p53, cleaved-PARP and caspase-3, and with the activation of both intrinsic (caspase-9) and extrinsic (caspase-8) apoptotic pathways. MH induced cell cycle arrest at S phase in HCT-116 cells, simultaneously, in LoVo cells, it arrested at G2/M phase through the modulation of cell cycle regulator genes (cyclin D1, cyclin E, CDK2, CDK4, p21, p27 and Rb). The expression of p-Akt was suppressed while the expression of p-p38MAPK, p-Erk1/2 and endoplasmic stress markers (ATF6 and XBP1) was increased for apoptosis induction.
Overall, these findings indicate that MH could be a promising preventive or curative food therapy for colon cancer.
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