Journal of Food Bioactives, ISSN 2637-8752 print, 2637-8779 online
Journal website www.isnff-jfb.com

Review

Volume 14, June 2021, pages 53-59

Recent study on the anticancer activity of nobiletin and its metabolites

Figures

Figure 1.
Figure 1. Structures of nobiletin and its in vivo metabolites.
Figure 2.
Figure 2. Schematic diagram showing the mechanisms underlying the anti-cancer effects of nobiletin and its derivatives through cell cycle arrest, anti-inflammation, anti-angiogenesis and induction of autophagy.

Table

Table 1. The anticancer activity of nobiletin and its derivatives
 
Protective EffectsPMF CompoundsCancer TypesDosageResultsReferences
Cell Cycle ArrestNobiletinPancreatic cancer6.12 µMInhibited the growth and metastasis. Induced autophagy, G0/G1 cell cycle arrest. Inhibited NF-kB signal pathwayJiang et al., 2020
Glioma100 μMInhibited glioma cell growth and migration. Arrested the cell cycle in the G0/G1 phase. Suppressed MAPK and Akt pathwaysLien et al., 2016
4′-DMNColon cancer0.05% (w/w, in diet)Inhibited cell growth. Induced G0/G1 cell cycle arrest and apoptosisWu et al., 2018
3′,4′-DDMNColon cancer7.5 µMInhibited cell growth. Induced significant G2-M cell-cycle arrest and apoptosisDiMarco-Crook et al., 2020
5-DMNLung cancer12.5 µMInhibited cell growth. Induced G2/M cell cycle phase arrest. Induced autophagy. Activated JNK signaling pathwayChen et al., 2015
4′-DMN,Lung cancer50 µMInhibited cell growth caused cell cycle arrest and cellular apoptosis. Modulated the expression of proteins related to cell proliferation and deathSong et al., 2016
3′,4′-DDMN25 µM
Anti-inflammationNobiletinProstate cancer80 µMInhibited cell growth. Suppressed TLR4/TRIF/IRF3, TLR9/IRF7 signal pathways. Inhibited the release of IFN-α and IFN-βOzkan et al., 2020
Nobiletin and its metabolitesColon cancer2.03 µM, NOB; 3.28 µM, 3′-DMN; 24.13 µM, 4′-DMN; 12.03 µM;,3′,4′-DDMNSuppressed LPS-induced iNOS and COX-2 expression. Increased heme oxygenase-1 (HO-1) and NQO1 expressionWu et al., 2017
3′,4′-DDMNSkin tumor1 or 3 µMInhibited TPA-induced iNOS, COX-2, VEGF, MMP-9 and ODC expression, nuclear translocation and phosphorylation of p65/RelALai et al., 2008
Anti-angiogenesisNobiletinBreast cancer200 µMInhibited cell growth. Inhibited VEGF-dependent angiogenesis. Inhibited EGFR activity and Src/FAK/STAT3 signalingSp et al., 2017
Inhibited the expression of CD36 and its downstream target proteins. Inhibited CD36-mediated Angiogenesis. Inhibited CD36-dependent breast cancer cell migration and Invasion, inhibited tumorsphere formation and survivalSp et al., 2018
NobiletinColorectal cancer64 µMInhibited MEK activity and ERK phosphorylationMiyata et al., 2008
AutophagyNobiletinHepatic Ischemia and reperfusion injury5 mg/kgAlleviated oxidative damage, inflammation, and cell death caused by hepatic ischemia and reperfusion. Activated the SIRT-1/FOXO3a and PGC-1α pathwaysDusabimana et al., 2019
Ovarian cancer40 μMSelectively suppressed cell growth and proliferation. Induced G0/G1 phase arrest and reduced G2/M phase. Induced apoptosis.Jiang et al., 2018
NobiletinGastric cancer50 μMIncreased the levels of ER-stress related proteins IRE1-α, ATF-4, C/EBP homology protein, GRP78 and caspase-4. Decreased cell viability. Increased the number of sub-G1 phase cells. Induced apoptosisMoon and Cho, 2016
5-DMNColon cancer50 or 100 mg/kgDecreased the tumor size and tumor weight. Increased the ratio of cleaved-PARP and LC3 expression in tumor tissues. Induced p53-regulated cell death signaling pathwaySong et al., 2020
ROSNobiletinOvarian Cancer50 μMInhibited cell growth. Induced cell apoptosis and autophagy. Induced ROS generation contributing to pyroptosisZhang et al., 2020
Oral cancer100 μMIncreased the expression of the apoptosis molecule PARP and caspase-3. Increased the level of ROS and the degree of DNA damage. Inhibited cell growthYang et al., 2020
Gastric cancer50 μMReduced ROS levels. Inhibited p38, extracellular receptor kinase 1, and c-Jun amino-terminal expression. Inhibited cell growthOuyang, Li and Ling, 2020