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Tumor Biology
Published in: Tumor Biology 5/2016

01-05-2016 | Original Article

Desacetyl nimbinene inhibits breast cancer growth and metastasis through reactive oxygen species mediated mechanisms

Authors: Arunkumar Arumugam, Ramadevi Subramani, Sushmita Nandy, Sara Powell, Marissa Velazquez, Alexis Orozco, Adriana Galvez, Rajkumar Lakshmanaswamy

Published in: Tumor Biology | Issue 5/2016

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Abstract

Accumulation of reactive oxygen species (ROS) has been implicated in induction of apoptosis and regulation of key signaling molecules in cancer cells. Phytochemicals are potent source of anticancer drugs as wells as potential inducers of ROS. Neem (Azadirachta indica) is a medicinal plant used for the treatment of various diseases. The main objective of this study is to investigate the anticancer effect of desacetyl nimbinene (DAN; an active ingredient of neem) against breast cancer. Normal and breast cancer cell lines were used for the study. The effect of DAN on cell proliferation, apoptosis, ROS generation, migration, and invasion was analyzed. Antioxidant enzymes superoxide dismutase (SOD)1 and SOD2 were overexpressed to test the effect of DAN-induced ROS generation on breast cancer growth. Key survival and apoptotic protein markers were analyzed to validate the anticancer effect of DAN. Our data demonstrated that DAN inhibited the growth of breast cancer cells by inducing ROS generation. Further investigations revealed that DAN treatment lead to the loss of mitochondrial membrane potential resulting in mitochondria-dependent apoptotic cell death. Increased phosphorylation of c-Jun-N-terminal kinase (JNK) and reduced phosphorylation of p38 were also observed in response to DAN treatment. Inhibition of ROS production by overexpressing antioxidant enzymes SOD1 and SOD2 reduced the DAN-induced cytotoxicity. Additionally, DAN significantly inhibited migration and invasion of MDA-MB-231 breast cancer cells. Overall, our data suggest that DAN exerts its anticancer effect on breast cancer by induction of mitochondria-mediated apoptosis mediated by ROS accumulation.
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Metadata
Title
Desacetyl nimbinene inhibits breast cancer growth and metastasis through reactive oxygen species mediated mechanisms
Authors
Arunkumar Arumugam
Ramadevi Subramani
Sushmita Nandy
Sara Powell
Marissa Velazquez
Alexis Orozco
Adriana Galvez
Rajkumar Lakshmanaswamy
Publication date
01-05-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 5/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-4468-x

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