Anti‐tumour effects of nobiletin, a citrus flavonoid, on gastric cancer include: antiproliferative effects, induction of apoptosis and cell cycle deregulation

Abstract

SUMMARYAim: To demonstrate the antitumour effects of nobiletin (5,6,7,8,3¢,4¢-hexamethoxyflavone), a citrus flavonoid extracted from Citrus depressa Hayata, on human gastric cancer cell lines TMK-1, MKN-45, MKN-74 and KATO-III. Materials and methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, the TdTmediated dUTP biotin nick-end labelling (TUNEL) method and cell-cycle analysis revealed that nobiletin acted on these cells in several ways, namely by direct cytotoxicity, induction of apoptosis and modulation of cell cycle. The efficacy of combined treatment of nobiletin with a conventional anticancer drug, CDDP, was also examined. Treatment with nobiletin 24 h prior to CDDP administration showed a synergistic effect compared to the control. Conclusions: Although the effective dose and administration route of nobiletin require further investigation, our study represents a potential successful linking of this compound with the treatment of gastric cancer.

Phytophenolic Nutrients in Citrus: Biochemical and Molecular Evidence

“…Loss of cell viability at low doses was found to be a consequence of apoptosis (Yoshimizu et al 2004 ) . A screening of 78 citrus species showed inhibitory effects of the Epstein-Barr virus antigen (EBV-EA) activation, indicating that citrus phytochemicals may inhibit susceptibility factors involved in the events leading to the development of cancer (Iwase et al 1999 ) .…”

Natural Products for Cancer-Targeted Therapy: Citrus Flavonoids as Potent Chemopreventive Agents

“…Nobiletin has been observed to be cytotoxic by modulating cell cycle on TMK-1, MKN-45, MKN-74, and KATO-III human gastric carcinoma cells (Yoshimizu et al, 2004). Another study showed that the compound induced G1 phase arrest on MDA-MB-435, MCF-7, and HT-29 cells (Morley et al, 2007).…”

“…Tangeretin was also able to induce apoptosis on HL-60 human promyelocytic leukemia cells . While nobiletin, another flavonoid obtained from C. reticulata peels, has been observed to be cytotoxic not only through modulating cell cycle, but also by inducing apoptosis on TMK-1, MKN-45, MKN-74, and KATO-III human gastric carcinoma cells (Yoshimizu et al, 2004).…”

<i>Citrus</i> Flavonoids and Human Cancers

“…Lee et al [92] revealed that PMFmediated induction of GADD45α partially underlies the anti-proliferative effect of PMF on colorectal cancer cells. Nobiletin was found to act as an anti-carcinogenic compound through anti-proliferative activity, induction of apoptosis and cell cycle deregulation [93]. It was reported that tangeretin suppressed breast cancer proliferation by up-regulating p53/p21 proteins and inducing G1/S phase cell cycle arrest [94].…”