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Cited by 254

The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.

Cystathionine Beta-Synthase (CBS) Contributes to Advanced Ovarian Cancer Progression and Drug Resistance

Open access
Bhattacharyya, Sanjib, Saha, Sounik, Giri, Karuna, Lanza, Ian R., Nair, K. Sreekumar, Jennings, Nicholas B., Rodriguez-Aguayo, Cristian, Lopez-Berestein, Gabriel, Basal, Eati, Weaver, Amy L., Visscher, Daniel W., Cliby, William, Sood, Anil K., Bhattacharya, Resham, Mukherjee, Priyabrata·2013·PLoS ONE
DOI 10.1371/journal.pone.0079167
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Abstract

BACKGROUND: Epithelial ovarian cancer is the leading cause of gynecologic cancer deaths. Most patients respond initially to platinum-based chemotherapy after surgical debulking, however relapse is very common and ultimately platinum resistance emerges. Understanding the mechanism of tumor growth, metastasis and drug resistant relapse will profoundly impact the therapeutic management of ovarian cancer. METHODS/PRINCIPAL FINDINGS: Using patient tissue microarray (TMA), in vitro and in vivo studies we report a role of of cystathionine-beta-synthase (CBS), a sulfur metabolism enzyme in ovarian carcinoma. We report here that the expression of cystathionine-beta-synthase (CBS), a sulfur metabolism enzyme, is common in primary serous ovarian carcinoma. The in vitro effects of CBS silencing can be reversed by exogenous supplementation with the GSH and H2S producing chemical Na2S. Silencing CBS in a cisplatin resistant orthotopic model in vivo by nanoliposomal delivery of CBS siRNA inhibits tumor growth, reduces nodule formation and sensitizes ovarian cancer cells to cisplatin. The effects were further corroborated by immunohistochemistry that demonstrates a reduction of H&E, Ki-67 and CD31 positive cells in si-RNA treated as compared to scrambled-RNA treated animals. Furthermore, CBS also regulates bioenergetics of ovarian cancer cells by regulating mitochondrial ROS production, oxygen consumption and ATP generation. This study reports an important role of CBS in promoting ovarian tumor growth and maintaining drug resistant phenotype by controlling cellular redox behavior and regulating mitochondrial bioenergetics. CONCLUSION: The present investigation highlights CBS as a potential therapeutic target in relapsed and platinum resistant ovarian cancer.

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Metadata

Authors
Bhattacharyya, S., Saha, S., Giri, K., Lanza, I. R., Nair, K. S., Jennings, N. B., Rodriguez-Aguayo, C., Lopez-Berestein, G., Basal, E., Weaver, A. L., Visscher, D. W., Cliby, W., Sood, A. K., Bhattacharya, R., & Mukherjee, P.
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2013-11-13
Volume
8
Issue
11
Pages
e79167
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0079167
OpenAlex
W2087795198
Cited by
254
References
48
FWCI
14.50
Type
journal article
Language
en
Open access
gold

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