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

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 d...

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Bibliographic Details
Published in:BioMed research international 2018-01, Vol.2018 (2018), p.1-11
Main Authors: Shrestha, Ram Lal (Swagat), Malavige, Neelika, Tennekoon, Kamani H., Ediriweera, Meran K., Adhikari, A., Samarakoon, Sameera R., Sivakumaran, Nivethika, Thabrew, M. Ira
Format: Article
Language:English
Subjects:
Alkaloids - pharmacology
Analysis
Annexin V
Apoptosis
Breast cancer
Breast Neoplasms - drug therapy
Breast Neoplasms - pathology
Cancer
Caspase
Caspase-7
Cell culture
Chemical compounds
Corydalis
Corydalis - chemistry
Cytotoxicity
Deoxyribonucleic acid
DNA
DNA fragmentation
Drug resistance
Flow cytometry
Gene expression
Glutathione
Glutathione transferase
Health aspects
Humans
MCF-7 Cells
Medical research
Metastasis
Morphology
Oxidative stress
p53 Protein
Pharmacology
Reactive Oxygen Species
RNA
Roots
Survivin
Terpenes - pharmacology
Time dependence
Toxicity
Tumor proteins
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Summary: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.
ISSN:2314-6133
2314-6141
DOI:10.1155/2018/3171348