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Curcumin induces apoptosis in pancreatic cancer cells through the induction of forkhead box O1 and inhibition of the PI3K/Akt pathway.
Mol Med Rep. 2015 Oct; 12(4):5415-22.MM

Abstract

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 anti‑proliferation, cell cycle arrest and apoptosis, by FOXO1, in pancreatic cancer cells. The MTT assay and ELISA‑Brdu assay were used to assess cell proliferation. Reverse transcription‑quantitative polymerase chain reaction and western blot analyses were used to detect the expression of PCNA, Ki‑67, B‑cell lymphoma‑2 (Bcl‑2), B‑cell‑associated X protein (Bax), cyclin D1, p21, p27 and FOXO1. Cell apoptosis was detected using a Cell Death ELISA detection kit. A Caspase‑3/9 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 cyclin‑dependent kinase inhibitors, and inhibited expression of cyclin D1. In addition, curcumin induced apoptosis by decreasing the Bcl‑2/Bax protein ratio and increasing caspase‑9/3 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 3‑kinase/Akt signaling, leading to cell cycle arrest and apoptosis. In conclusion, these findings offer support for a mechanism that may underlie the anti‑neoplastic effects of curcumin and justify further investigation to examine the potential roles for activators of FOXO1 in the prevention and treatment of pancreatic cancer.

Authors+Show Affiliations

Department of Surgical Oncology, Chinese PLA General Hospital, Beijing 100853, P.R. China.Department of Surgical Oncology, Chinese PLA General Hospital, Beijing 100853, P.R. China.Department of Hepatobiliary Surgery, Beijing Shunyi Hospital Affiliated to China Medical University, Beijing 101300, P.R. China.Department of Surgical Oncology, Chinese PLA General Hospital, Beijing 100853, P.R. China.Department of Surgical Oncology, Chinese PLA General Hospital, Beijing 100853, P.R. China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

26166196

Citation

Zhao, Zhiming, et al. "Curcumin Induces Apoptosis in Pancreatic Cancer Cells Through the Induction of Forkhead Box O1 and Inhibition of the PI3K/Akt Pathway." Molecular Medicine Reports, vol. 12, no. 4, 2015, pp. 5415-22.
Zhao Z, Li C, Xi H, et al. Curcumin induces apoptosis in pancreatic cancer cells through the induction of forkhead box O1 and inhibition of the PI3K/Akt pathway. Mol Med Rep. 2015;12(4):5415-22.
Zhao, Z., Li, C., Xi, H., Gao, Y., & Xu, D. (2015). Curcumin induces apoptosis in pancreatic cancer cells through the induction of forkhead box O1 and inhibition of the PI3K/Akt pathway. Molecular Medicine Reports, 12(4), 5415-22. https://doi.org/10.3892/mmr.2015.4060
Zhao Z, et al. Curcumin Induces Apoptosis in Pancreatic Cancer Cells Through the Induction of Forkhead Box O1 and Inhibition of the PI3K/Akt Pathway. Mol Med Rep. 2015;12(4):5415-22. PubMed PMID: 26166196.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Curcumin induces apoptosis in pancreatic cancer cells through the induction of forkhead box O1 and inhibition of the PI3K/Akt pathway. AU - Zhao,Zhiming, AU - Li,Chenggang, AU - Xi,Hao, AU - Gao,Yuanxing, AU - Xu,Dabin, Y1 - 2015/07/08/ PY - 2014/09/18/received PY - 2015/06/05/accepted PY - 2015/7/14/entrez PY - 2015/7/15/pubmed PY - 2016/6/28/medline SP - 5415 EP - 22 JF - Molecular medicine reports JO - Mol Med Rep VL - 12 IS - 4 N2 - 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 anti‑proliferation, cell cycle arrest and apoptosis, by FOXO1, in pancreatic cancer cells. The MTT assay and ELISA‑Brdu assay were used to assess cell proliferation. Reverse transcription‑quantitative polymerase chain reaction and western blot analyses were used to detect the expression of PCNA, Ki‑67, B‑cell lymphoma‑2 (Bcl‑2), B‑cell‑associated X protein (Bax), cyclin D1, p21, p27 and FOXO1. Cell apoptosis was detected using a Cell Death ELISA detection kit. A Caspase‑3/9 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 cyclin‑dependent kinase inhibitors, and inhibited expression of cyclin D1. In addition, curcumin induced apoptosis by decreasing the Bcl‑2/Bax protein ratio and increasing caspase‑9/3 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 3‑kinase/Akt signaling, leading to cell cycle arrest and apoptosis. In conclusion, these findings offer support for a mechanism that may underlie the anti‑neoplastic effects of curcumin and justify further investigation to examine the potential roles for activators of FOXO1 in the prevention and treatment of pancreatic cancer. SN - 1791-3004 UR - https://www.unboundmedicine.com/medline/citation/26166196/Curcumin_induces_apoptosis_in_pancreatic_cancer_cells_through_the_induction_of_forkhead_box_O1_and_inhibition_of_the_PI3K/Akt_pathway_ L2 - http://www.spandidos-publications.com/mmr/12/4/5415 DB - PRIME DP - Unbound Medicine ER -