The Anti-Proliferation, Cycle Arrest and Apoptotic Inducing Activity of Peperomin E on Prostate Cancer PC-3 Cell Line.

Yunzhi Li,Meng Gou,Jigang Pan

doi:10.3390/molecules24081472

Abstract

Peperomin E is a natural secolignan existing distributed in the plants of the genus Peperomia. Previous investigations demonstrated that peperomin E showed potential antitumor activity in some cancer lines, but it is unclear whether peperomin E has an effect on prostate cancer cell lines. The aim of the present study is to investigate its effects on proliferation inhibition, apoptosis-inducing and cell-cycle arrest activity using a prostate cancer PC-3 cell line. The proliferation inhibition was evaluated by MTT assay, apoptosis was detected by Annexin V/propidium iodide (PI) staining and Hoechst 33258 staining, cell cycle distributions were measured by flow cytometry, and western blot analysis was used to determine specific cellular apoptotic protein expressions of Bcl-2, Bax, caspase-3 and cleaved-caspase-3. According to the results of this study, peperomin E exhibited significant anti-proliferation activity on PC-3 cell lines in vitro in a dose-dependent manner. Peperomin E treatments lead to marked morphological changes. Apoptotic cell count and cell-cycle distribution at G2/M phase significantly increased with increasing concentrations of peperomin E. The down-regulated expression level of Bcl-2 and up-regulated expression level of Bax and cleaved-caspase-3 compared with the controls were also observed after peperomin E treatment. These data suggest that peperomin E exhibited proliferation inhabitation, apoptosis-inducing and cell-cycle arrest activity on PC-3 cell lines. The anti-proliferation effect of peperomin E on PC-3 cells should result partly from its cell-cycle arrest and apoptosis-inducing activity, whereas the increasing of the Bax/Bcl-2 ratio and activation of caspases-3 play an important role in the development of apoptosis.

Highlights

The incidence of prostate cancer is the second highest among male malignant tumors in the world.According to statistics, there were number 1.4 million new cases worldwide in 2016, with 381,000 deaths that year [1]
Peperomia is richdecreased in various intypes the PC-3 cells in a dose-dependent manner
These data suggest that peperomin could up-regulate of lignans, and secolignan is a type of novel lignan found in Peperomia for the first time [14]

Summary

Introduction

The incidence of prostate cancer is the second highest among male malignant tumors in the world. There were number 1.4 million new cases worldwide in 2016, with 381,000 deaths that year [1]. In China, the incidence rate of prostate cancer has been increasing with the aging population and it is seriously harmful to male health [2]. Androgen deprivation therapy (ADT) is the standard treatment for patients with prostate cancer, but, generally, after 12–24 months’ ADT in almost all prostate cancer cases will progress to castration-resistant prostate cancer (CRPC). Some new drugs, such as docetaxel, cabazitaxel, the CYP17A1 inhibitor abiraterone, and the androgen receptor inhibitor enzalutamide, have been used as a first-line therapy to CRPC, they have a limited effect on disease outcomes. Cabazitaxel, which is a dimethoxy derivative of docetaxel, passes more through the blood-brain barrier of patients than docetaxel, but the overall and progression-free survival of patients with CRPC treated with cabazitaxel are only 15.77 and 5.52 months, respectively [3]

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