Corosolic acid induces potent anti-cancer effects in CaSki cervical cancer cells through the induction of apoptosis, cell cycle arrest and PI3K/Akt signalling pathway

Yong Qian Xu,Jian Hai Zhang,Xing Sheng Yang

doi:10.3329/bjp.v11i2.26793

Abstract

The main objective of the present study was to investigate the anti-tumor activity of corosolic acid in CaSki human cervical cancer cells. Fluorescence and phase contrast microscopic techniques were used to study the effect of the compound on cellular morphology and apoptosis. Results revealed that corosolic acid exerted potent, dose- and time-dependent growth inhibitory effects in CaSki cell proliferation. Cells got detached from one another making clusters of small number of cells floating in the medium. After the cells were treated with 10, 50 and 100 µM concentrations of corosolic acid, cells began to emit orange red fluorescence more heavily at the centre of cells indicating apoptosis. Corosolic acid also induced G2/M cell cycle arrest in a dose-dependent manner. Increasing doses of corosolic acid treatment to these cells resulted in significant and dose-dependent down-regulation of PI3K and Akt protein expressions.Video Clip<a href="https://youtube.com/v/N4EivZECRZE">Western blot assay</a>: 2 min 1 sec

Highlights

Natural products continue to play a leading role as novel and promising anti-cancer chemotherapeutic agents
The current study demonstrated the effect of this compound on cell cycle phase distribution, mitochondrial membrane potential loss and PI3K/Akt signalling pathway
Phosphorylated p-PI3K, PI3K, p-Akt and Akt were procured from Cell Signalling Technology (USA), while as X-ray film for chemiluminescent system was obtained from Fuji Photo Film (Japan)

Summary

Introduction

Natural products continue to play a leading role as novel and promising anti-cancer chemotherapeutic agents. They are used as anti-cancer agents either in their natural form or as synthetic or semi-synthetic derivatives. There are many anti-cancer candidates from natural sources which are currently in clinical development or have been recently approved for clinical use. Among all the anti-cancer agents approved so far, natural product based anti-cancer agents constitute around 60-65% of the total (Kinghorn, 2008; Cragg et al, 2005; Newman and Cragg, 2007; Butler, 2008). Natural products are embellished with their inherent drug likeness and as such most of these compounds have a better receptor-binding tendency (Feher and Schmidt, 2003)

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