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IJMS, Vol. 19, Pages 1763: Chrysin Attenuates Cell Viability of Human Colorectal Cancer Cells through Autophagy Induction Unlike 5-Fluorouracil/Oxaliplatin

IJMS, Vol. 19, Pages 1763: Chrysin Attenuates Cell Viability of Human Colorectal Cancer Cells through Autophagy Induction Unlike 5-Fluorouracil/Oxaliplatin

International Journal of Molecular Sciences doi: 10.3390/ijms19061763

Authors: Yueh-Ming Lin Chih-I Chen Yi-Ping Hsiang Yung-Chia Hsu Kung-Chuan Cheng Pei-Hsuan Chien Hsiao-Lin Pan Chien-Chang Lu Yun-Ju Chen

Chemotherapeutic 5-fluorouracil (5-FU) combined with oxaliplatin is often used as the standard treatment for colorectal cancer (CRC). The disturbing side effects and drug resistance commonly observed in chemotherapy motivate us to develop alternative optimal therapeutic options for CRC treatment. Chrysin, a natural and biologically active flavonoid abundant in propolis, is reported to have antitumor effects on a few CRCs. However, whether and how chrysin achieves similar effectiveness to the 5-FU combination is not clear. In this study, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), western blotting, fluorescence microscopy, and reactive oxygen species (ROS) production were assayed. We found that chrysin exhibited similar inhibition of cell viability as the 5-FU combination in a panel of human CRC cells. Furthermore, the results showed that chrysin significantly increased the levels of LC3-II, an autophagy-related marker, in CRC cells, which was not observed with the 5-FU combination. More importantly, blockage of autophagy induction restored chrysin-attenuated CRC cell viability. Further mechanistic analysis revealed that chrysin, not the 5-FU combination, induced ROS generation, and in turn, inhibited the phosphorylation of protein kinase B (Akt) and mammalian target of rapamycin (mTOR). Collectively, these results imply that chrysin may be a potential replacement for the 5-FU and oxaliplatin combination to achieve antitumor activity through autophagy for CRC treatment in the future.

Authors:   Lin, Yueh-Ming ; Chen, Chih-I ; Hsiang, Yi-Ping ; Hsu, Yung-Chia ; Cheng, Kung-Chuan ; Chien, Pei-Hsuan ; Pan, Hsiao-Lin ; Lu, Chien-Chang ; Chen, Yun-Ju
Journal:   International Journal of Molecular Sciences
Volume:   19
edition:   6
Year:   2018
Pages:   1763
DOI:   10.3390/ijms19061763
Publication date:   14-Jun-2018
Facts, background information, dossiers
  • cell viability
  • oxaliplatin
  • colorectal cancer
  • cells
  • autophagy
  • Western blotting
  • Rapamycin
  • production
  • phosphorylation
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