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Int. J. Mol. Sci. 2015, 16(8), 16806-16815; doi:10.3390/ijms160816806

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

1
Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185, Korea
2
Interdisciplinary Graduate Program in Molecular Medicine, Chonnam National University, Gwangju 501-746, Korea
3
School of Biological Sciences and Biotechnology, Chonnam National University, Gwangju 500-757, Korea
4
Department of Food Science and Biotechnology, Daegu University, Gyeongsan-si, 712-714, Korea
5
Department of Biochemistry, School of Dentistry, Chonnam National University, Gwangju 500-757, Korea
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Paul B. Tchounwou
Received: 28 May 2015 / Revised: 15 July 2015 / Accepted: 16 July 2015 / Published: 24 July 2015
View Full-Text   |   Download PDF [1196 KB, uploaded 24 July 2015]   |  

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. View Full-Text
Keywords: rotenone; rotenoisin B; apoptosis; hepatic cancer; Huh7; pAKT; mitogen activated protein kinase (MAPK) rotenone; rotenoisin B; apoptosis; hepatic cancer; Huh7; pAKT; mitogen activated protein kinase (MAPK)
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Badaboina, S.; Bai, H.-W.; Na, Y.H.; Park, C.-H.; Kim, T.H.; Lee, T.-H.; Chung, B.Y. Novel Radiolytic Rotenone Derivative, Rotenoisin B with Potent Anti-Carcinogenic Activity in Hepatic Cancer Cells. Int. J. Mol. Sci. 2015, 16, 16806-16815.

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