Cytotoxic and Apoptotic Effects of Govaniadine Isolated from Corydalis govaniana Wall. Roots on Human Breast Cancer (MCF-7) Cells.

Nivethika Sivakumaran,Sameera R Samarakoon,Ira Thabrew,Ram Lal (Swagat) Shrestha,Neelika Malavige,Achyut Adhikari,Meran K Ediriweera,Kamani H Tennekoon

doi:10.1155/2018/3171348

Nivethika Sivakumaran, Sameera R Samarakoon + Show 6 more

Open Access

https://doi.org/10.1155/2018/3171348

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Abstract

Current breast cancer therapies have limitations in terms of increased drug resistance resulting in short-term efficacy, thus demanding the discovery of new therapeutic agents. In this study, cytotoxic activity and apoptotic effects of govaniadine isolated from Corydalis govaniana Wall. roots were determined on human breast cancer (MCF-7) cells. The SRB assay result revealed that govaniadine led to dose- and time-dependent cytotoxic effect in MCF-7 cells along with less cytotoxicity against MCF-10A cells. Govaniadine-induced apoptosis was also accompanied by upregulation of Bax, p53, and Survivin mRNA expression as assessed by real time PCR analysis. Flow cytometric analysis with Annexin V and PI staining indicated that govaniadine is a potent inducer of apoptosis in MCF-7 cell lines. Distinctive morphological changes contributed to apoptosis and DNA laddering were observed in govaniadine-treated MCF-7 cells. Caspase-7 was significantly activated in treated MCF-7 cells. Govaniadine-treated MCF-7 cells also showed enhanced levels of intracellular reactive oxygen species (ROS) and glutathione S-transferase (GST) and decreased levels of glutathione (GSH). The results indicate that govaniadine has potent and selective cytotoxic effects against MCF-7 cells and the potential to induce caspase 7 dependent apoptosis in MCF-7 cells by activation of pathways that lead to oxidative stress.

Highlights

Breast cancer is the most common cancer in women worldwide, resulting in 350,000 deaths each year [1]
The potential of using natural products as anticancer agents was recognized in the 1950s by the US National Cancer Institute (NCI), and more than 60% of current therapies for cancer are derived from natural sources, including plants [2, 3]
Our data demonstrated that govaniadine exerted significant cytotoxic effects against MCF-7 breast cancer cells by inducing marked morphological changes associated with apoptosis and a decrease in the number of cells in a time- and dose-dependent manner

Summary

Introduction

Breast cancer is the most common cancer in women worldwide, resulting in 350,000 deaths each year [1]. The potential of using natural products as anticancer agents was recognized in the 1950s by the US National Cancer Institute (NCI), and more than 60% of current therapies for cancer are derived from natural sources, including plants [2, 3]. Current therapies for breast cancer are often limited by shortterm efficacy due to the nonspecific targeting, high toxicity to normal tissues, undesirable side effects, and drug resistance. Inhibition of apoptosis is associated with cancer; apoptosis is a popular target in the development of novel anticancer drugs. MCF-7 cells lack caspase-3, which is one of the main initiators of apoptotic pathways; they become highly resistant to apoptosis and develop resistance against most chemotherapeutic drugs within a few months to a few years [5, 6]

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