Fatty acid synthase inhibitor cerulenin inhibits topoisomerase I catalytic activity and augments SN-38-induced apoptosis

Title
Fatty acid synthase inhibitor cerulenin inhibits topoisomerase I catalytic activity and augments SN-38-induced apoptosis
Authors
최은옥
Keywords
Cerulenin Topoisomerase I SN-38 Fatty acid synthase PUFA
Issue Date
2013
Publisher
APOPTOSIS
Series/Report no.
APOPTOSIS ; Vol18 no.2 Startpage 226 Endpage 237
Abstract
Fatty acid synthase (FASN) is overexpressed in a wide variety of human cancers, making it an attractive target for anticancer therapy. One of the most widely used inhibitors of FASN, cerulenin, is a natural product of Cephalosporium caerulens. Cerulenin is selectively toxic to human cancer cells in vitro. However, the mechanism by which FASN inhibition causes apoptosis in tumor cells remains unclear. Because of the widespread clinical interest in combining cerulenin with other chemotherapeutic agents, we performed this study to gain insight into the downstream effects of FASN inhibition that lead to apoptosis. Here, we observed the increased antitumor effect of cerulenin when combined with the topoisomerase inhibitor SN-38. We identified topoisomerase I as a potential mediator of cerulenin-induced apoptosis, possibly by upregulating intracellular polyunsaturation. Finally, we show that suppressing topoisomerase I catalytic activity results in synergistic effects between cerulenin and LY294002. Our results suggest that topoisomerase I could participate in cerulenin-induced apoptosis by upregulating intracellular polyunsaturation. These results will help determine the molecular basis of the cerulenin and SN-38 drug combination. Further investigation of this pathway will provide new insight into cancer cell metabolism and may aid in the design of additional cancer chemotherapeutic agents.
URI
http://dspace.inha.ac.kr/handle/10505/33546
ISSN
1360-8185
Appears in Collections:
College of Natural Science(자연과학대학) > Food and Nutrition (식품영양학) > Journal Papers, Reports(식품영양학 논문, 보고서)
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