Salen-Mn compounds induces cell apoptosis in human prostate cancer cells through promoting AMPK activity and cell autophagy.

Xiaoshuang Tang,Xinyang Wang,Bin Jin,Dalin He,Peng Guo,Jing Jia,Qi Shi,Wei Liu,Feng Li,Chao Yang

doi:10.18632/oncotarget.21138

Abstract

Currently only docetaxel has been approved to be used in the chemotherapy of prostate cancer and new drugs are urgent need. Salen-Mn is a novel type of synthetic reagent bionic and exerts remarkable anticancer activities. However, the effect of Salen-Mn on human prostate cancer has not been elucidated yet. In this study, we found that treatment of PC-3 and DU145 human prostate cancer cells with Salen-Mn inhibited cell growth in dose and time dependent manner. Moreover, Salen-Mn induced cell apoptosis, and increased the expression of apoptotic proteins, such as cleaved caspase-3, cleaved PARP, and Bax, in PC-3 and DU145 prostate cancer cells. Furthermore, we found that Salen-Mn induced expression of LC3-I/II, which is protein marker of cell autophagy, in both dose and time dependent manners; in addition, Salen-Mn increased the phosphorylation of AMPK, suggesting that Salen-Mn increase cell autophagy through activating AMPK pathway. On the other hand, when PC-3 and DU145 cells were treated with Salen-Mn and 3-MA, an inhibitor of cell autophagy, the inhibitory effect of Salen-Mn on cell growth and the induction of apoptotic proteins were decreased. In addition, we found that Salen-Mn inhibited the growth of PC-3 cell xenografts in nude mice. In summary, our results indicate that Salen-Mn suppresses cell growth through inducing AMPK activity and autophagic cell death related cell apoptosis in prostate cancer cells and suggest that Salen-Mn and its derivatives could be new options for the chemical therapeutics in the treatment of prostate cancer.

Highlights

Prostate cancer is one of the most common malignancies in male in the USA [1]
These results indicated that Salen-Mn could induce apoptosis in human prostate cancer DU145 and PC-3 cells in a dose-dependent manner
We found that Salen-Mn inhibited cell growth, induced cell apoptosis, and increased the expression of apoptotic proteins, in PC-3 and DU145 prostate cancer cells

Summary

Introduction

Prostate cancer is one of the most common malignancies in male in the USA [1]. According to the epidemiology statistics of global cancer from World Health Organization (GLOBOCAN 2008), the morbidity from prostate cancer in 2008 was ranked second, accounting for 14% of all cancer types in male [2]. The platinum based anti-tumor agents have enormous impact on current cancer therapy, in order to overcome clinical problems associated with the relatively limited activity of platinum based agents against the broad spectrum of human malignancies, acquired resistance, and side effects, novel non-platinum metal-based anticancer complexes have been and are being developed [5,6,7]. N, N’bis (salicylidene)-ethylene diamine, which is synthetically accessible as it is inexpensive and nontoxic [8], is a promising candidate for this purpose. In this respect, transition Salen-Mn metal complexes are of considerable research interest because of their structural diversity [9]. Whether SalenMn can induces the death of prostate cancer cells and the underlying mechanism are still unknown

Methods

Results

Conclusion