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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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 |
Journal | International journal of oncology
(Int J Oncol)
Vol. 46
Issue 6
Pg. 2670-8
( 2015)
ISSN: 1791-2423 [Electronic] Greece |
PMID | 25892545
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Flavonoids
- Inhibitor of Apoptosis Proteins
- Proto-Oncogene Proteins c-bcl-2
- fas Receptor
- morin
- Caspases
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Topics |
- Antineoplastic Agents
(pharmacology)
- Apoptosis
- Caspases
(metabolism)
- Colorectal Neoplasms
(drug therapy, metabolism)
- Flavonoids
(pharmacology)
- HCT116 Cells
- Humans
- Inhibitor of Apoptosis Proteins
(metabolism)
- Membrane Potential, Mitochondrial
(drug effects)
- Proto-Oncogene Proteins c-bcl-2
(metabolism)
- fas Receptor
(metabolism)
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