Novel Radiolytic Rotenone Derivative, Rotenoisin B with Potent Anti-Carcinogenic Activity in Hepatic Cancer Cells

Autor: Yun Hee Na, Byung Yeoup Chung, Tae Hoon Kim, Srilatha Badaboina, Hyoung-Woo Bai, Chul-Hong Park, Tae-Hoon Lee
Rok vydání: 2015
Předmět:
Programmed cell death
Cell Survival
Poly ADP ribose polymerase
pAKT
Antineoplastic Agents
rotenone
rotenoisin B
apoptosis
hepatic cancer
Huh7
mitogenactivated protein kinase (MAPK)
Pharmacology
Article
Catalysis
lcsh:Chemistry
Inorganic Chemistry
chemistry.chemical_compound
Derris
Humans
mitogen activated protein kinase (MAPK)
Physical and Theoretical Chemistry
lcsh:QH301-705.5
Molecular Biology
Spectroscopy
Membrane Potential
Mitochondrial
chemistry.chemical_classification
Reactive oxygen species
Cell Death
biology
Cytochrome c
Liver Neoplasms
Organic Chemistry
Cell Cycle Checkpoints
Hep G2 Cells
General Medicine
Rotenone
Flow Cytometry
biology.organism_classification
Computer Science Applications
lcsh:Biology (General)
lcsh:QD1-999
Biochemistry
chemistry
Gamma Rays
Apoptosis
Cancer cell
biology.protein
Reactive Oxygen Species
Signal Transduction
Zdroj: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES(16): 8
International Journal of Molecular Sciences
Volume 16
Issue 8
Pages 16806-16815
International Journal of Molecular Sciences, Vol 16, Iss 8, Pp 16806-16815 (2015)
ISSN: 1422-0067
DOI: 10.3390/ijms160816806
Popis: 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 G(2)/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.
Databáze: OpenAIRE
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