Curcumin Induces Autophagy, Apoptosis, and Cell Cycle Arrest in Human Pancreatic Cancer Cells.

Yaping Zhu,Shurui Bu

doi:10.1155/2017/5787218

Abstract

Objective Curcumin is an active extract from turmeric. The aim of this study was to identify the underlying mechanism of curcumin on PCa cells and the role of autophagy in this process. Methods The inhibitory effect of curcumin on the growth of PANC1 and BxPC3 cell lines was detected by CCK-8 assay. Cell cycle distribution and apoptosis were tested by flow cytometry. Autophagosomes were tested by cell immunofluorescence assay. The protein expression was detected by Western blot. The correlation between LC3II/Bax and cell viability was analyzed. Results Curcumin inhibited the cell proliferation in a dose- and time-dependent manner. Curcumin could induce cell cycle arrest at G2/M phase and apoptosis of PCa cells. The autophagosomes were detected in the dosing groups. Protein expression of Bax and LC3II was upregulated, while Bcl2 was downregulated in the high dosing groups of curcumin. There was a significant negative correlation between LC3II/Bax and cell viability. Conclusions Autophagy could be triggered by curcumin in the treatment of PCa. Apoptosis and cell cycle arrest also participated in this process. These findings imply that curcumin is a multitargeted agent for PCa cells. In addition, autophagic cell death may predominate in the high concentration groups of curcumin.

Highlights

Pancreatic cancer (PCa) is the third leading cause of cancerrelated death in the United States with a 5-year survival rate of 7.7% [1] and ranks 12th of all cancer incidences
Pancreatic cancer is a malignant tumor with a poor prognosis despite surgical intervention, and the standard chemotherapy is based on gemcitabine
We found that curcumin had a diverse range of targets for PCa cells, including cell cycle arrest, apoptosis, and autophagy pathways

Summary

Introduction

Pancreatic cancer (PCa) is the third leading cause of cancerrelated death in the United States with a 5-year survival rate of 7.7% [1] and ranks 12th of all cancer incidences. 81% PCa patients were diagnosed at a terminal stage, which determines a poor prognosis. According to some statistical data, both morbidity and mortality of PCa continue to rise, while those of most other cancers have declined [2]. Surgery is applicable only to a few early-stage patients, and chemotherapy is the most important remedy for patients with metastatic cancer. According to a randomized study [3], the median survival increased from 4.41 months of treatment with 5-FU to 5.65 months of gemcitabine, and the 1-year survival rate improved from 2% in 5-FU-treated patients to 18% in gemcitabine-treated patients. Owing to multidrug resistance and the intolerable adverse effects of the drug, searching for new alternative and adjuvant chemotherapy drugs has become an urgent mission

Methods

Results

Conclusion