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Int J Mol Sci. 2018 Jun 14;19(6). pii: E1763. doi: 10.3390/ijms19061763.

Chrysin Attenuates Cell Viability of Human Colorectal Cancer Cells through Autophagy Induction Unlike 5-Fluorouracil/Oxaliplatin.

Author information

1
Division of Colorectal Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan. porta2005@gmail.com.
2
Division of Colon and Rectal Surgery, Department of Surgery, E-Da Hospital, Kaohsiung 824, Taiwan. jimmyee0901@gmail.com.
3
School of Medicine for International Students, I-Shou University, Kaohsiung 824, Taiwan. jimmyee0901@gmail.com.
4
Department of Pharmacy, E-Da Hospital, Kaohsiung 824, Taiwan. ed108228@edah.org.tw.
5
Department of Pharmacy, E-Da Cancer Hospital, Kaohsiung 824, Taiwan. ed108840@edah.org.tw.
6
Division of Colorectal Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan. topguncheng@gmail.com.
7
Department of Medical Research, E-Da Hospital, Kaohsiung 824, Taiwan. peihsuan68@gmail.com.
8
Department of Medical Research, E-Da Hospital, Kaohsiung 824, Taiwan. dkiyh@yahoo.com.tw.
9
Division of Colorectal Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan. doctor.lu@msa.hinet.net.
10
School of Medicine for International Students, I-Shou University, Kaohsiung 824, Taiwan. yjchen0326@isu.edu.tw.
11
Department of Pharmacy, E-Da Cancer Hospital, Kaohsiung 824, Taiwan. yjchen0326@isu.edu.tw.
12
Department of Medical Research, E-Da Hospital, Kaohsiung 824, Taiwan. yjchen0326@isu.edu.tw.

Abstract

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.

KEYWORDS:

CRC; ROS; autophagy; chemotherapy; chrysin

PMID:
29899208
PMCID:
PMC6032318
DOI:
10.3390/ijms19061763
[Indexed for MEDLINE]
Free PMC Article

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