Isoaaptamine Induces T-47D Cells Apoptosis and Autophagy via Oxidative Stress
Chih Fung Wu,Man Gang Lee,Mohamed El-Shazly,Kuei Hung Lai,Seng Chung Ke,Chiang Wen Su,Shou Ping Shih,Ping-Jyun Sung,Ming Chang Hong,Zhi-Hong Wen,Mei-Chin Lu +10 more
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TLDR
The cytotoxic effect of isoaaptamine is associated with the induction of apoptosis and autophagy through oxidative stress and represents an interesting drug lead in the war against breast cancer.Abstract:
Aaptos is a genus of marine sponge which belongs to Suberitidae and is distributed in tropical and subtropical oceans. Bioactivity-guided fractionation of Aaptos sp. methanolic extract resulted in the isolation of aaptamine, demethyloxyaaptamine, and isoaaptamine. The cytotoxic activity of the isolated compounds was evaluated revealing that isoaaptamine exhibited potent cytotoxic activity against breast cancer T-47D cells. In a concentration-dependent manner, isoaaptamine inhibited the growth of T-47D cells as indicated by short-(MTT) and long-term (colony formation) anti-proliferative assays. The cytotoxic effect of isoaaptamine was mediated through apoptosis as indicated by DNA ladder formation, caspase-7 activation, XIAP inhibition and PARP cleavage. Transmission electron microscopy and flow cytometric analysis using acridine orange dye indicated that isoaaptamine treatment could induce T-47D cells autophagy. Immunoblot assays demonstrated that isoaaptamine treatment significantly activated autophagy marker proteins such as type II LC-3. In addition, isoaaptamine treatment enhanced the activation of DNA damage (γH2AX) and ER stress-related proteins (IRE1 α and BiP). Moreover, the use of isoaaptamine resulted in a significant increase in the generation of reactive oxygen species (ROS) as well as in the disruption of mitochondrial membrane potential (MMP). The pretreatment of T-47D cells with an ROS scavenger, N-acetyl-l-cysteine (NAC), attenuated the apoptosis and MMP disruption induced by isoaaptamine up to 90%, and these effects were mediated by the disruption of nuclear factor erythroid 2-related factor 2 (Nrf 2)/p62 pathway. Taken together, these findings suggested that the cytotoxic effect of isoaaptamine is associated with the induction of apoptosis and autophagy through oxidative stress. Our data indicated that isoaaptamine represents an interesting drug lead in the war against breast cancer.read more
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References
More filters
Journal ArticleDOI
Marine natural products.
TL;DR: This review covers the literature published in 2014 for marine natural products, with 1116 citations referring to compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, mangroves and other intertidal plants and microorganisms.
Journal ArticleDOI
Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach?
TL;DR: It is argued that modulating the unique redox regulatory mechanisms of cancer cells might be an effective strategy to eliminate these cells.
Journal ArticleDOI
Natural Products as Sources of New Drugs from 1981 to 2014
David J. Newman,Gordon M. Cragg +1 more
TL;DR: This contribution is a completely updated and expanded version of the four prior analogous reviews that were published in this journal in 1997, 2003, 2007, and 2012, and the time frame has been extended to cover the 34 years from January 1, 1981, to December 31, 2014, for all diseases worldwide, and from 1950 (earliest so far identified) to December 2014 for all approved antitumor drugs worldwide.
Journal ArticleDOI
An nrf2/small maf heterodimer mediates the induction of phase ii detoxifying enzyme genes through antioxidant response elements
Ken Itoh,Tomoki Chiba,Satoru Takahashi,Tetsuro Ishii,Kazuhiko Igarashi,Yasutake Katoh,Tatsuya Oyake,Norio Hayashi,Kimihiko Satoh,Ichiro Hatayama,Masayuki Yamamoto,Yo-ichi Nabeshima +11 more
TL;DR: It is demonstrated that Nrf2 is essential for the transcriptional induction of phase II enzymes and the presence of a coordinate transcriptional regulatory mechanism for phase II enzyme genes and the nrf2-deficient mice may prove to be a very useful model for the in vivo analysis of chemical carcinogenesis and resistance to anti-cancer drugs.
Journal ArticleDOI
Modulation of oxidative stress as an anticancer strategy.
TL;DR: The controversial role of ROS in tumour development and in responses to anticancer therapies is addressed, and the idea that targeting the antioxidant capacity of tumour cells can have a positive therapeutic impact is elaborate.