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Nobiletin (NOB) and 5-demethylnobiletin (DMNB) are unique polymethoxyflavones (PMFs) found in citrus peel that exhibit anti-tumoral action in several cancer cell models. The differences between NOB and DMNB with respect to their anti-proliferative potencies and underlying molecular mechanism were compared in this contribution. The results of the cell viability assay suggested that DMNB resulted in more enhanced growth inhibitory effects than NOB in human colon cancer cell lines (HCT-116, HT-29 and COLO 205). Flow cytometry data found that DMNB inhibited proliferation in COLO 205 cells by predominantly inducing apoptosis. A xenograft mouse model further demonstrated that DMNB exhibited more preferential anti-colon cancer effects than NOB via its ability to induce p53-regulated cell death signaling (apoptosis and autophagy) and inhibit key cellular markers associated with inflammation and angiogenesis. Taken together, our findings provide evidence for the first time that natural bioactive DMNB might serve as a promising polymethoxyflavone for chemoprevention of colorectal cancer.
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