The flavonoid morin from Moraceae induces apoptosis by modulation of Bcl-2 family members and Fas receptor in HCT 116 cells

Hyun,Hwang-Bo; Lee,Won  Sup; Go,Se-Il; Nagappan,Arulkumar; Park,Cheol; Han,Min  Ho; Hong,Su  Hyun; Kim,Gonsup; Kim,Gi  Young; Cheong,Jaehun; Ryu,Chung  Ho; Shin,Sung  Chul; Choi,Yung  Hyun

doi:10.3892/ijo.2015.2967

The flavonoid morin from Moraceae induces apoptosis by modulation of Bcl-2 family members and Fas receptor in HCT 116 cells

Authors:
- Hwang-Bo Hyun
- Won Sup Lee
- Se-Il Go
- Arulkumar Nagappan
- Cheol Park
- Min Ho Han
- Su Hyun Hong
- Gonsup Kim
- Gi Young Kim
- Jaehun Cheong
- Chung Ho Ryu
- Sung Chul Shin
- Yung Hyun Choi
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Affiliations: Department of Biochemistry, Dongeui University College of Korean Medicine, Busan 614-052, Republic of Korea, Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-702, Republic of Korea, Department of Molecular Biology, College of Natural Sciences, Dongeui University, Busan 614-714, Republic of Korea, Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan 614-052, Republic of Korea, School of Veterinary Medicine, Research Institute of Life Science, Gyeongsang National University, Jinju 660-701, Republic of Korea, Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Jeju 690-756, Republic of Korea, Department of Molecular Biology, College of Natural Sciences, Pusan National University, Busan 609-735, Republic of Korea, Division of Applied Life Science (BK 21 Program), Research Institute of Life Science, Gyeongsang National University, Jinju 660-701, Republic of Korea, Department of Chemistry, Research Institute of Life Science, Gyeongsang National University, Jinju 660-701, Republic of Korea
Published online on: April 16, 2015 https://doi.org/10.3892/ijo.2015.2967
Pages: 2670-2678

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Abstract

It is evident based on literature that flavonoids from fruit can safely modulate cancer cell biology and induce apoptosis. Therefore, we investigated the anticancer activity of morin, a flavonoid which is plentiful in twigs of mulberry focusing on apoptosis, and its mechanisms. Morin upregulated the Fas receptor, and activates caspase-8, -9 and -3 in HCT-116 cells. Morin also activates Bid, and induced the loss of mitochondrial membrane potential (MMP, ∆Ψm) with Bax protein activation and cytochrome c release. In addition, morin induced ROS generation which was not blocked by N-acetylcysteine. Morin also suppressed Bcl-2 and cIAP-1, anti-apoptotic proteins, which may contribute to augmentation of morin-triggered apoptosis. As an upstream signaling pathway, suppressed Akt activity by morin was associated to apoptosis. This study suggests that morin induces caspase-dependent apoptosis through extrinsic pathway by upregulating Fas receptor as well as through the intrinsic pathway by modulating Bcl-2 and IAP family members, and ROS generation, and that Akt is the critical upstream signaling that regulates the apoptotic effect of morin in human colon cancer HCT-116 cells.

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