Ricinus communis L. fruit extract inhibits migration/invasion, induces apoptosis in breast cancer cells and arrests tumor progression in vivo

Munmi Majumder,Parasuraman Jaisankar,Shibjyoti Debnath,Kaushik Biswas,Suman Kumar Samanta,Bhaskarjyoti Gogoi,Deepjyoti K Das,Rimpi Saikia,Rahul L Gajbhiye,Rupak Mukhopadhyay

doi:10.1038/s41598-019-50769-x

Abstract

Medicinal plant-based therapies can be important for treatment of cancer owing to high efficiency, low cost and minimal side effects. Here, we report the anti-cancer efficacy of Ricinus communis L. fruit extract (RCFE) using estrogen positive MCF-7 and highly aggressive, triple negative MDA-MB-231 breast cancer cells. RCFE induced cytotoxicity in these cells in dose and time-dependent manner. It also demonstrated robust anti-metastatic activity as it significantly inhibited migration, adhesion, invasion and expression of matrix metalloproteinases (MMPs) 2 and 9 in both cell lines. Further, flow cytometry analysis suggested RCFE-mediated induction of apoptosis in these cells. This was supported by attenuation of anti-apoptotic Bcl-2, induction of pro-apoptotic Bax and caspase-7 expressions as well as PARP cleavage upon RCFE treatment. RCFE (0.5 mg/Kg body weight) treatment led to significant reduction in tumor volume in 4T1 syngeneic mouse model. HPLC and ESI-MS analysis of active ethyl acetate fraction of RCFE detected four compounds, Ricinine, p-Coumaric acid, Epigallocatechin and Ricinoleic acid. Individually these compounds showed cytotoxic and migration-inhibitory activities. Overall, this study for the first time demonstrates the anti-cancer efficacy of the fruit extract of common castor plant which can be proposed as a potent candidate for the treatment of breast cancer.

Highlights

Breast cancer is the leading cause of cancer death among women worldwide[1]
The current study demonstrates the anti-proliferative activity of R. communis L. fruit extract (RCFE) against two breast cancer cell lines MCF-7 and MDA-MB-231
To evaluate the cytotoxic effect of RCFE on breast cancer, MCF-7 and MDA-MB-231 cell lines were treated with various concentrations of RCFE for 24 or 48 hr

Summary

Introduction

Breast cancer is the leading cause of cancer death among women worldwide[1]. The main treatment regimens for breast cancer like surgery, radiation therapy, chemotherapy, targeted hormone therapy are either expensive or have various side-effects[2,3]. Purified plant polyphenols, baicalin and fisetin were shown to possess anti-cancer and apoptosis inducing activity in breast cancer cell lines[10,11]. In search of a novel medicinal plant-based therapeutic approach against breast cancer, fruit extract of Ricinus communis L. 50% ethanolic extract of roots of this plants have shown anti-diabetic activity in in-vivo rat models[19]. A detailed study on the anti-cancer efficacy of the fruits of R. communis L. is not reported. The current study demonstrates the anti-proliferative activity of R. communis L. fruit extract (RCFE) against two breast cancer cell lines MCF-7 and MDA-MB-231. RCFE significantly inhibited migration, adhesion and invasion along with reduction of matrix metalloproteinases 2 and 9 expression It induced apoptosis as shown by reduction of anti-apoptotic Bcl-2, induction of pro-apoptotic Bax expression and DNA fragmentation. HPLC and ESI-MS analysis of the active ethyl acetate fraction of RCFE showed presence of four probable compounds all of which individually showed anti-cancer activities

Methods

Results

Conclusion