Open Access5-Demethylnobiletin more potently inhibits colon cancer cell growth than nobiletin in vitro and in vivo
Author(s) -
Yi-Siou Chiou,
Yu-Nu Zheng,
Mei-Ling Tsai,
Ching-Shu Lai,
ChiTang Ho,
MinHsiung Pan
Publication year - 2018
Publication title -
journal of food bioactives
Language(s) - English
Resource type - Journals
eISSN - 2637-8779
pISSN - 2637-8752
DOI - 10.31665/jfb.2018.2143
Subject(s) - nobiletin , apoptosis , angiogenesis , in vivo , cell growth , cancer research , cancer , programmed cell death , flow cytometry , autophagy , colorectal cancer , cell , biology , cancer cell , viability assay , chemistry , microbiology and biotechnology , biochemistry , flavonoid , genetics , antioxidant
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.