TY - JOUR
T1 - Sansalvamide induces pancreatic cancer growth arrest through changes in the cell cycle
AU - Heiferman, Michael J.
AU - Salabat, Mohammad R.
AU - Ujiki, Michael B.
AU - Strouch, Matthew J.
AU - Cheon, Eric C.
AU - Silverman, Richard B.
AU - Bentrem, David J.
N1 - Funding Information:
The authors thank the support of National Natural Science Foundation of China (No. 51101065, 51371086). The authors also thank the support of analytical and testing center of Huazhong University of Science and Technology.
PY - 2010/1
Y1 - 2010/1
N2 - Survival of patients with pancreatic cancer remains poor due to inadequate chemotherapeutic options. Sansalvamide A, a cyclic depsipeptide produced by a marine fungus, has demonstrated significant anticancer activity. We previously observed antiproliferative effects in a series of sansalvamide A analogs in pancreatic cancer cells, one of which was further evaluated in this study. Two human pancreatic cancer cell lines (AsPC-1 and CD18) were incubated with increasing concentrations (10-50 μM) of the sansalvamide analog. Cell proliferation was then measured by thymidine incorporation and cell counting, and cell cycle analysis was determined by flow cytometry. Western blot analysis was used to evaluate expression of cyclin D1, cdk4, cdk6, cyclin E, cyclin A, cdk2, and p21. Sansalvamide caused G1 phase cell cycle arrest in both cell lines, and Western blot analyses demonstrated up-regulation of p21, down-regulation of cyclins D1, E, and A, and cdk4, consistent with G 0/G1 cell cycle arrest. Cumulatively the results show that Sansalvamide A attenuates pancreatic cancer cell growth and represents a potential anticancer therapy.
AB - Survival of patients with pancreatic cancer remains poor due to inadequate chemotherapeutic options. Sansalvamide A, a cyclic depsipeptide produced by a marine fungus, has demonstrated significant anticancer activity. We previously observed antiproliferative effects in a series of sansalvamide A analogs in pancreatic cancer cells, one of which was further evaluated in this study. Two human pancreatic cancer cell lines (AsPC-1 and CD18) were incubated with increasing concentrations (10-50 μM) of the sansalvamide analog. Cell proliferation was then measured by thymidine incorporation and cell counting, and cell cycle analysis was determined by flow cytometry. Western blot analysis was used to evaluate expression of cyclin D1, cdk4, cdk6, cyclin E, cyclin A, cdk2, and p21. Sansalvamide caused G1 phase cell cycle arrest in both cell lines, and Western blot analyses demonstrated up-regulation of p21, down-regulation of cyclins D1, E, and A, and cdk4, consistent with G 0/G1 cell cycle arrest. Cumulatively the results show that Sansalvamide A attenuates pancreatic cancer cell growth and represents a potential anticancer therapy.
KW - Cell cycle arrest
KW - Pancreatic cancer
KW - Sansalvamide A
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M3 - Article
C2 - 20150619
AN - SCOPUS:77649249807
SN - 0250-7005
VL - 30
SP - 73
EP - 78
JO - Anticancer Research
JF - Anticancer Research
IS - 1
ER -