title: Novel Radiolytic Rotenone Derivative, Rotenoisin B with Potent Anti-Carcinogenic Activity in Hepatic Cancer Cells.
abstract: Rotenone, isolated from roots of derris plant, has been shown to possess various biological activities, which lead to attempting to develop a potent drug against several diseases. However, recent studies have demonstrated that rotenone has the potential to induce several adverse effects such as a neurodegenerative disease. Radiolytic transformation of the rotenone with gamma-irradiation created a new product, named rotenoisin B. The present work was designed to investigate the anticancer activity of rotenoisin B with low toxicity and its molecular mechanism in hepatic cancer cells compared to a parent compound, rotenone. Our results showed rotenoisin B inhibited hepatic cancer cells' proliferation in a dose dependent manner and increased in apoptotic cells. Interestingly, rotenoisin B showed low toxic effects on normal cells compared to rotenone. Mitochondrial transmembrane potential has been decreased, which leads to cytochrome c release. Down regulation of anti-apoptotic Bcl-2 levels as well as the up regulation of proapoptotic Bax levels were observed. The cleaved PARP (poly ADP-ribose polymerase) level increased as well. Moreover, phosphorylation of extracellular signal regulated kinase (ERK) and p38 slightly up regulated and intracellular reactive oxygen species (ROS) increased as well as cell cycle arrest predominantly at the G2/M phase observed. These results suggest that rotenoisin B might be a potent anticancer candidate similar to rotenone in hepatic cancer cells with low toxicity to normal cells even at high concentrations compared to rotenone.
authors.affiliation: Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185, Korea. srilatha_bio@rediffmail.com.
authors.forename: Srilatha
authors.initials: S
authors.lastname: Badaboina
authors.affiliation: Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185, Korea. hbai@kaeri.re.kr.
authors.forename: Hyoung-Woo
authors.initials: HW
authors.lastname: Bai
authors.affiliation: Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185, Korea. thlee83@chonnam.ac.kr.|Interdisciplinary Graduate Program in Molecular Medicine, Chonnam National University, Gwangju 501-746, Korea. thlee83@chonnam.ac.kr.
authors.forename: Yun Hee
authors.initials: YH
authors.lastname: Na
authors.affiliation: Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185, Korea. parkch@kaeri.re.kr.|School of Biological Sciences and Biotechnology, Chonnam National University, Gwangju 500-757, Korea. parkch@kaeri.re.kr.
authors.forename: Chul-Hong
authors.initials: CH
authors.lastname: Park
authors.affiliation: Department of Food Science and Biotechnology, Daegu University, Gyeongsan-si, 712-714, Korea. skyey7@daegu.ac.kr.
authors.forename: Tae Hoon
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Interdisciplinary Graduate Program in Molecular Medicine, Chonnam National University, Gwangju 501-746, Korea. thlee83@chonnam.ac.kr.|Department of Biochemistry, School of Dentistry, Chonnam National University, Gwangju 500-757, Korea. thlee83@chonnam.ac.kr.
authors.forename: Tae-Hoon
authors.initials: TH
authors.lastname: Lee
authors.affiliation: Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185, Korea. bychung@kaeri.re.kr.
authors.forename: Byung Yeoup
authors.initials: BY
authors.lastname: Chung
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005434:Flow Cytometry; D005720:Gamma Rays; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D012402:Rotenone / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; C000607031:rotenoisin B; D012402:Rotenone
keywords: Huh7; apoptosis; hepatic cancer; mitogen activated protein kinase (MAPK); pAKT; rotenoisin B; rotenone