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Polymethoxyflavones: Chemistry and Molecular Mechanisms for Cancer Prevention and Treatment

  • Natural Products: From Chemistry to Pharmacology (C Ho, Section Editor)
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Abstract

Polymethoxyflavones (PMFs) are one group of the flavonoid compounds, with tangeretin (Tan) and nobiletin (Nob) being the most abundant PMFs in citrus peel. Numerous biological activities of PMFs have been intensively studied, including anti-inflammatory and anticancer activities. Because of their methoxy groups, PMFs are more lipophilic than hydroxyl flavones, which may affect their biological activities. In addition, researchers found that hydroxylated PMFs (HPMFs) are one of the major metabolites of PMFs in animal urine and feces. Although PMF and HPMFs do show anticancer activity against different types of cancers, but their low hydrophilicity is still a crucial factor that may affect their biological effectiveness. Therefore, from the pharmaceutical aspect, chemical modifications of PMFs have been carried out to obtain acetylated PMFs (Ac-PMFs) for enhancing their biological effects. From the past centuries to the present, cancer is still a critical disease that needs to be solved. Carcinogenesis can be simply divided into three stages: initiation, promotion, and progression. These three stages involve different biological events, such as DNA mutation, cell proliferation, cell growth, and metastasis. In this paper, we aim to illustrate the biological effects of different PMFs, HPMFs, PMF derivatives, and metabolites against different types of cancer and related molecular mechanisms.

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Abbreviations

ΔΨm:

mitochondrial membrane potential

5-Ac-Tan:

5-acetyl-6,7,8,4′-tetramethylnortangeretin

5-OH-HXMF:

5-hydorxy-3,6,7,8,3′,4′-hexamethoxyflavone

5-OH-Nob:

5-hydroxy-6,7,8,3′.4′-pcntamcthoxyflavanone

5-OH-PMFs:

5-hydroxylated PMFs

5-OH-Tan:

5-hydroxy-6,7,8,4′-tetramethoxyflavon

AFB1:

aflatoxin B1γGT: γ-glutamyl transpeptidase

BaP:

benzo[a]pyrene

BM:

base-mentmembrane

DFF-45:

DNA fragmentation factor

DHTMF:

3,5-dihydroxy-6,7,3′,4′-tetramethoxyflavone

ECM:

extracellular matrix

GADD153:

enhanced DNA damage-inducible gene 153

HPMFs:

hydroxylated polymethoxyflavone

MMP:

matrix metalloproteinases

Nob:

nobiletin

PAH:

polycyclic aromatic hydrocarbons

PARP:

poly(ADP-ribose) polymerase

PMF:

polymethoxyflavone

Sin:

sinensetin

Tan:

tangeretin

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Funding

This study was financially supported by the Ministry of Science and Technology [105-2628-B-002-003-MY3, 107-2811-B-002-564].

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Authors and Affiliations

  1. Institute of Food Science and Technology, National Taiwan University, No. 1, Section 4, Roosevelt Road, Taipei, 10617, Taiwan

    Yen-Chen Tung, Ya-Chun Chou, Roch-Chui Yu & Min-Hsiung Pan

  2. School of Food Safety, Taipei Medical University, Taipei, Taiwan

    Wei-Lun Hung

  3. Department of Tourism, Food and Beverage Management, Chang Jung Christian University, Tainan, 71101, Taiwan

    An-Chin Cheng

  4. Department of Food Science, Rutgers University, New Brunswick, NJ, USA

    Chi-Tang Ho

  5. Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan

    Min-Hsiung Pan

  6. Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan

    Min-Hsiung Pan

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  1. Yen-Chen Tung
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Tung, YC., Chou, YC., Hung, WL. et al. Polymethoxyflavones: Chemistry and Molecular Mechanisms for Cancer Prevention and Treatment. Curr Pharmacol Rep 5, 98–113 (2019). https://doi.org/10.1007/s40495-019-00170-z

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