title: The flavonoid morin from Moraceae induces apoptosis by modulation of Bcl-2 family members and Fas receptor in HCT 116 cells.
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.
authors.affiliation: Department of Biochemistry, Dongeui University College of Korean Medicine, Busan 614-052, Republic of Korea.
authors.forename: Hwang-Bo
authors.initials: HB
authors.lastname: Hyun
authors.affiliation: Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-702, Republic of Korea.
authors.forename: Won Sup
authors.initials: WS
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-702, Republic of Korea.
authors.forename: Se-Il
authors.initials: SI
authors.lastname: Go
authors.affiliation: Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-702, Republic of Korea.
authors.forename: Arulkumar
authors.initials: A
authors.lastname: Nagappan
authors.affiliation: Department of Molecular Biology, College of Natural Sciences, Dongeui University, Busan 614-714, Republic of Korea.
authors.forename: Cheol
authors.initials: C
authors.lastname: Park
authors.affiliation: Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan 614-052, Republic of Korea.
authors.forename: Min Ho
authors.initials: MH
authors.lastname: Han
authors.affiliation: Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan 614-052, Republic of Korea.
authors.forename: Su Hyun
authors.initials: SH
authors.lastname: Hong
authors.affiliation: School of Veterinary Medicine, Research Institute of Life Science, Gyeongsang National University, Jinju 660-701, Republic of Korea.
authors.forename: Gonsup
authors.initials: G
authors.lastname: Kim
authors.affiliation: Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Jeju 690-756, Republic of Korea.
authors.forename: Gi Young
authors.initials: GY
authors.lastname: Kim
authors.affiliation: Department of Molecular Biology, College of Natural Sciences, Pusan National University, Busan 609-735, Republic of Korea.
authors.forename: Jaehun
authors.initials: J
authors.lastname: Cheong
authors.affiliation: Division of Applied Life Science (BK 21 Program), Research Institute of Life Science, Gyeongsang National University, Jinju 660-701, Republic of Korea.
authors.forename: Chung Ho
authors.initials: CH
authors.lastname: Ryu
authors.affiliation: Department of Chemistry, Research Institute of Life Science, Gyeongsang National University, Jinju 660-701, Republic of Korea.
authors.forename: Sung Chul
authors.initials: SC
authors.lastname: Shin
authors.affiliation: Department of Biochemistry, Dongeui University College of Korean Medicine, Busan 614-052, Republic of Korea.
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology*; D045325:HCT116 Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D019014:fas Receptor / Q000378:metabolism*; D047309:Flavones
chemical_list: D000970:Antineoplastic Agents; D020169:Caspases; D005419:Flavonoids; D051034:Inhibitor of Apoptosis Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor; C008548:morin; D047309:Flavones