Current Pharmacology Reports

, Volume 5, Issue 2, pp 98–113 | Cite as

Polymethoxyflavones: Chemistry and Molecular Mechanisms for Cancer Prevention and Treatment

  • Yen-Chen Tung
  • Ya-Chun Chou
  • Wei-Lun Hung
  • An-Chin Cheng
  • Roch-Chui Yu
  • Chi-Tang Ho
  • Min-Hsiung PanEmail author
Natural Products: From Chemistry to Pharmacology (C Ho, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Natural Products: From Chemistry to Pharmacology


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.


Anticancer Citrus peel Hydroxylated polymethoxyflavone Metabolites Polymethoxyflavones Polymethoxyflavone derivatives 



mitochondrial membrane potential








5-hydroxylated PMFs




aflatoxin B1γGT: γ-glutamyl transpeptidase






DNA fragmentation factor




extracellular matrix


enhanced DNA damage-inducible gene 153


hydroxylated polymethoxyflavone


matrix metalloproteinases




polycyclic aromatic hydrocarbons


poly(ADP-ribose) polymerase








Funding Information

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

Compliance with Ethical Standards

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


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Authors and Affiliations

  1. 1.Institute of Food Science and TechnologyNational Taiwan UniversityTaipeiTaiwan
  2. 2.School of Food SafetyTaipei Medical UniversityTaipeiTaiwan
  3. 3.Department of Tourism, Food and Beverage ManagementChang Jung Christian UniversityTainanTaiwan
  4. 4.Department of Food ScienceRutgers UniversityNew BrunswickUSA
  5. 5.Department of Medical Research, China Medical University HospitalChina Medical UniversityTaichungTaiwan
  6. 6.Department of Health and Nutrition BiotechnologyAsia UniversityTaichungTaiwan

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