title: Korean Byungkyul - Citrus platymamma Hort.et Tanaka flavonoids induces cell cycle arrest and apoptosis, regulating MMP protein expression in Hep3B hepatocellular carcinoma cells.
abstract: Citrus platymamma Hort.et Tanaka is an indigenous fruit of Jeju island in Korea. In this study the bioactivity of C. platymamma flavonoids were evaluated on human hepatoma Hep3B cell lines. Eleven flavonoids were identified from the peels of C. platymamma Hort.et Tanaka through high-performance liquid chromatography-Tandem mass spectrometry and the anticancer effect of these C. platymamma flavonoids on human hepatoma Hep3B were studied. Chromatin condensation was observed in Hep3B cells treated with C. platymamma flavonoids. DNA fragmentation was confirmed through agarose gel electrophoresis and TUNEL assay. An increase in the total apoptotic cells and G2/M cell cycle arrest with decreased protein expression of CDC25C, CDK1, cyclin B1 and p21 were observed in Hep3B cells treated with flavonoids of C. platymamma. Further, protein expression of Bcl-XL, Bax, caspase-3 and -9 were also modulated by C. platymamma flavonoids treatment indicating that cell death is through intrinsic apoptotic pathway. Moreover, C. platymamma flavonoids also regulated the phosphorylation of MAPKs, PI3K, and Akt in Hep3B cells. Relevant to inhibiting metastasis, C. platymamma treatment reduced wound closure of Hep3B cells and the protein expression of matrix metalloproteinase-2 and -9 were reduced in C. platymamma treated cells. The results show that C. platymamma flavonoids induce cell cycle arrest and apoptosis following activation of MAPKs and suppression of PI3K/Akt pathway which eventually inhibits cell migration in Hep3B cells. The finding provides evidence on biochemical activities of C. platymamma Hort.et Tanaka, which would be an essential agent for hepatocellular carcinoma (HCC) treatment.
authors.affiliation: Research Institute of Life Science and College of Veterinary Medicine, Gyeongsang National University, Gazwa, Jinju 660-701, Republic of Korea.
authors.forename: Gyeong Eun
authors.initials: GE
authors.lastname: Hong
authors.affiliation: Research Institute of Life Science and College of Veterinary Medicine, Gyeongsang National University, Gazwa, Jinju 660-701, Republic of Korea.
authors.forename: Ho Jeong
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Physical Therapy, International University of Korea, Jinju 660-759, Republic of Korea.
authors.forename: Jin A
authors.initials: JA
authors.lastname: Kim
authors.affiliation: Research Institute of Life Science and College of Veterinary Medicine, Gyeongsang National University, Gazwa, Jinju 660-701, Republic of Korea.
authors.forename: Silvia
authors.initials: S
authors.lastname: Yumnam
authors.affiliation: Research Institute of Life Science and College of Veterinary Medicine, Gyeongsang National University, Gazwa, Jinju 660-701, Republic of Korea.
authors.forename: Suchismita
authors.initials: S
authors.lastname: Raha
authors.affiliation: Research Institute of Life Science and College of Veterinary Medicine, Gyeongsang National University, Gazwa, Jinju 660-701, Republic of Korea.
authors.forename: Venu
authors.initials: V
authors.lastname: Venkatarame Gowda Saralamma
authors.affiliation: Gyeongnam Biological Resource Research Center, Korea Institute of Toxicology, Jinju 666-844, Republic of Korea.
authors.forename: Jeong Doo
authors.initials: JD
authors.lastname: Heo
authors.affiliation: Gyeongnam Biological Resource Research Center, Korea Institute of Toxicology, Jinju 666-844, Republic of Korea.
authors.forename: Sang Joon
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Nursing Science, International University of Korea, Jinju 660-759, Republic of Korea.
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Kim
authors.affiliation: College of Veterinary Medicine, Gyeongsang National University, Gazwa, Jinju 660-701, Republic of Korea.
authors.forename: Chun Kil
authors.initials: CK
authors.lastname: Won
authors.affiliation: Research Institute of Life Science and College of Veterinary Medicine, Gyeongsang National University, Gazwa, Jinju 660-701, Republic of Korea.
authors.forename: Gon Sup
authors.initials: GS
authors.lastname: Kim
mesh_terms: D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002957:Citrus / Q000737:chemistry*; D005419:Flavonoids / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D010936:Plant Extracts / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D005419:Flavonoids; D010936:Plant Extracts; D020782:Matrix Metalloproteinases