title: Flavonoids of Korean Citrus aurantium L. Induce Apoptosis via Intrinsic Pathway in Human Hepatoblastoma HepG2 Cells.
abstract: Korean Citrus aurantium L. has long been used as a medicinal herb for its anti-inflammatory, antioxidant, and anticancer properties. The present study investigates the anticancer role of flavonoids extracted from C. aurantium on human hepatoblastoma cell, HepG2. The Citrus flavonoids inhibit the proliferation of HepG2 cells in a dose-dependent manner. This result was consistent with the in vivo xenograft results. Apoptosis was detected by cell morphology, cell cycle analysis, and immunoblot. Flavonoids decreased the level of pAkt and other downstream targets of phosphoinositide-3-kinase/Akt pathway - P-4EBP1 and P-p70S6K. The expressions of cleaved caspase 3, Bax, and Bak were increased, while those of Bcl-2 and Bcl-xL were decreased with an increase in the expression of Bax/Bcl-xL ratio in treated cells. Loss of mitochondrial membrane potential was also observed in flavonoid-treated HepG2 cells. It was also observed that the P-p38 protein level was increased both dose and time dependently in flavonoid-treated cells. Collectively, these results suggest that flavonoid extracted from Citrus inhibits HepG2 cell proliferation by inducing apoptosis via an intrinsic pathway. These findings suggest that flavonoids extracted from C. aurantium L. are potential chemotherapeutic agents against liver cancer.
authors.affiliation: Research Institute of Life Science, College of Veterinary Medicine (BK21 plus project), Gyeongsang National University, Gazwa, Jinju, 660-701, Korea.
authors.forename: Seung Hwan
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Research Institute of Life Science, College of Veterinary Medicine (BK21 plus project), Gyeongsang National University, Gazwa, Jinju, 660-701, Korea.
authors.forename: Silvia
authors.initials: S
authors.lastname: Yumnam
authors.affiliation: Research Institute of Life Science, College of Veterinary Medicine (BK21 plus project), Gyeongsang National University, Gazwa, Jinju, 660-701, Korea.
authors.forename: Gyeong Eun
authors.initials: GE
authors.lastname: Hong
authors.affiliation: Research Institute of Life Science, College of Veterinary Medicine (BK21 plus project), Gyeongsang National University, Gazwa, Jinju, 660-701, Korea.
authors.forename: Suchismita
authors.initials: S
authors.lastname: Raha
authors.affiliation: Research Institute of Life Science, College of Veterinary Medicine (BK21 plus project), Gyeongsang National University, Gazwa, Jinju, 660-701, Korea.
authors.forename: Venu Venkatarame Gowda
authors.initials: VV
authors.lastname: Saralamma
authors.affiliation: Research Institute of Life Science, College of Veterinary Medicine (BK21 plus project), Gyeongsang National University, Gazwa, Jinju, 660-701, Korea.
authors.forename: Ho Jeong
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Gyeongnam Department of Environment Toxicology and Chemistry, Toxicity Screening Research Center, Korea Institute of Toxicology, Jinju, Korea.
authors.forename: Jeong Doo
authors.initials: JD
authors.lastname: Heo
authors.affiliation: Gyeongnam Department of Environment Toxicology and Chemistry, Toxicity Screening Research Center, Korea Institute of Toxicology, Jinju, Korea.
authors.forename: Sang Joon
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Gyeongnam Regional Cancer Center, Gyeongsang National University Hospital, Jinju, 660-702, Korea.
authors.forename: Won-Sup
authors.initials: WS
authors.lastname: Lee
authors.affiliation: Department of Nursing Science, International University of Korea, Jinju, 660-759, Korea.
authors.forename: Eun-Hee
authors.initials: EH
authors.lastname: Kim
authors.affiliation: Research Institute of Life Science, College of Veterinary Medicine (BK21 plus project), Gyeongsang National University, Gazwa, Jinju, 660-701, Korea.
authors.forename: Hyeon Soo
authors.initials: HS
authors.lastname: Park
authors.affiliation: Research Institute of Life Science, College of Veterinary Medicine (BK21 plus project), Gyeongsang National University, Gazwa, Jinju, 660-701, Korea.
authors.forename: Gon Sup
authors.initials: GS
authors.lastname: Kim
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002957:Citrus / Q000737:chemistry*; D005419:Flavonoids / Q000494:pharmacology*; D056945:Hep G2 Cells; D018197:Hepatoblastoma / Q000473:pathology*; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008807:Mice, Inbred BALB C; D010936:Plant Extracts / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; D005419:Flavonoids; D010936:Plant Extracts
keywords: Akt; Bax/Bcl-xL; Citrus aurantium; HepG2; apoptosis; p-38