Curcumin induces apoptosis in pancreatic cancer cells through the induction of forkhead box O1 and inhibition of the PI3K/Akt pathway
Previous population investigations have suggested that the application of curcumin may be associated with decreased incidence and improved prognosis in certain types of cancer. Forkhead box O1 (FOXO1) has been implicated in the regulation of several biological processes, including stress
resistance, metabolism, DNA repair, cell cycle and apoptosis. The aims of the present study were to investigate the effects and molecular mechanisms of curcumin on the induction of antiproliferation, cell cycle arrest and apoptosis, by FOXO1, in pancreatic cancer cells. The MTT assay and ELISABrdu
assay were used to assess cell proliferation. Reverse transcriptionquantitative polymerase chain reaction and western blot analyses were used to detect the expression of PCNA, Ki67, Bcell lymphoma2 (Bcl2), Bcellassociated X protein (Bax), cyclin D1, p21, p27 and FOXO1. Cell apoptosis
was detected using a Cell Death ELISA detection kit. A Caspase3/9 Fluorescent Assay kit was used to detect caspase activity. The findings revealed that curcumin significantly decreased cell proliferation, which was associated with increased expression of the p21/CIP1 and p27/KIP1 cyclindependent
kinase inhibitors, and inhibited expression of cyclin D1. In addition, curcumin induced apoptosis by decreasing the Bcl2/Bax protein ratio and increasing caspase9/3 activation in the pancreatic cancer cells. Using siRNA against FOXO1, and Akt inhibitor and activator, the present study confirmed
that curcumin induced the expression of FOXO1 by inhibition of phosphoinositide 3kinase/Akt signaling, leading to cell cycle arrest and apoptosis. In conclusion, these findings offer support for a mechanism that may underlie the antineoplastic effects of curcumin and justify further investigation
to examine the potential roles for activators of FOXO1 in the prevention and treatment of pancreatic cancer.
Document Type: Research Article
Affiliations: 1: Department of Surgical Oncology, Chinese PLA General Hospital, Beijing 100853, P.R. China 2: Department of Hepatobiliary Surgery, Beijing Shunyi Hospital Affiliated to China Medical University, Beijing 101300, P.R. China
Publication date: 01 October 2015
- Molecular Medicine Reports is a monthly, peer-reviewed journal available in print and online, that includes studies devoted to molecular medicine, underscoring aspects including pharmacology, pathology, genetics, neurosciences, infectious diseases, molecular cardiology and molecular surgery. In vitro and in vivo studies of experimental model systems pertaining to the mechanisms of a variety of diseases offer researchers the necessary tools and knowledge with which to aid the diagnosis and treatment of human diseases.
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