Acetylation Enhances the Anticancer Activity and Oral Bioavailability of 5-Demethyltangeretin

Hui Yun Tsai, Jia Fang Yang, Yin Bo Chen, Jia Lin Guo, Shiming Li, Guor Jien Wei, Chi Tang Ho, Jue Liang Hsu, Chi I. Chang, Yu Shen Liang, Hsu Sheng Yu, Yu Kuo Chen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


A kind of hydroxylated polymethoxyflavone (PMFs) existing in the citrus genus, 5-Demethyltangeretin (5-DTAN), has been reported to possess several bioactivities in vitro and in vivo. The aim of this study was to investigate whether acetylation could enhance the anticancer activity and oral bioavailability of 5-DTAN. PC-3 human prostate cancer cells were treated with tangeretin (TAN), 5-DTAN, and 5-acetylated TAN (5-ATAN), and the results showed that the cytotoxic effect 5-ATAN (IC50 value of 5.1 µM) on the cell viability of PC-3 cells was stronger than that of TAN (IC50 value of 17.2 µM) and 5-DTAN (IC50 value of 11.8 µM). Compared to 5-DTAN, 5-ATAN treatment caused a more pronounced DNA ladder, increased the sub-G1 phase population, and induced G2/M phase arrest in the cell cycle of PC-3 cells. We also found that 5-ATAN triggered the activation of caspase-3 and the progression of the intrinsic mitochondrial pathway in PC-3 cells, suggesting the induction of apoptosis. In a cell wound healing test, 5-ATAN dose-dependently reduced the cell migration, and the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) was decreased after 48 h of 5-ATAN treatment. Moreover, oral administration of 5-ATAN showed a significantly stronger inhibitory effect on tumor size and tumor weight in tumor-bearing nude mice than those of vehicle or the 5-DTAN group (p < 0.05). Furthermore, pharmacokinetic results showed that single-dose oral administration of 5-ATAN exhibited a higher maximum concentration (Cmax) and area under the curve (AUC) of 5-DTAN in plasma than that of 5-DTAN. More extensive distribution of 5-DTAN to most tissues of mice was also observed in mice treated with 5-ATAN for 7 days. In conclusion, acetylation strongly enhances the anticancer activity and oral bioavailability of 5-DTAN and could be a promising strategy to promote the potential bioactivities of natural products.

Original languageEnglish
Article number13284
JournalInternational Journal Of Molecular Sciences
Issue number21
StatePublished - Nov 2022


  • acetylation
  • anticancer
  • bioavailability
  • citrus
  • polymethoxyflavones


Dive into the research topics of 'Acetylation Enhances the Anticancer Activity and Oral Bioavailability of 5-Demethyltangeretin'. Together they form a unique fingerprint.

Cite this