Galbanic acid: Induced antiproliferation in estrogen receptor‐negative breast cancer cells and enhanced cellular redox state in the human dermal fibroblasts

• Published in: Journal of biochemical and molecular toxicology Vol. 33; no. 11; pp. e22402 - n/a
• Main Authors: Sajjadi, Maryam, Karimi, Ehsan, Oskoueian, Ehsan, Iranshahi, Mehrdad, Neamati, Ali
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01-11-2019
• Subjects: Acids; Anticancer properties; Antineoplastic Agents - pharmacology; Antioxidants; Antioxidants - pharmacology; Apoptosis; Apoptosis - drug effects; bcl-2-Associated X Protein - genetics; Bioactive compounds; Biocompatibility; Biological activity; Breast cancer; Breast carcinoma; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Caspase; Caspase 3 - genetics; Catalase; Catalase - genetics; Cell death; Cell proliferation; Cell Proliferation - drug effects; Cell Survival - drug effects; Cell viability; Coumarins - pharmacology; Cytotoxicity; Estrogens; Female; Ferula; Ferula - chemistry; Fibroblasts; Fibroblasts - metabolism; Flow cytometry; Free Radicals; Gene expression; Gene Expression Regulation, Neoplastic - drug effects; Gene flow; Genes; Glutathione; Glutathione peroxidase; Glutathione Peroxidase - genetics; human dermal fibroblasts; Humans; MCF-7 Cells; Menopause; Oxidation-Reduction; Peroxidase; Plant Extracts - pharmacology; Proto-Oncogene Proteins c-bcl-2 - genetics; Receptors, Estrogen - metabolism; Redox properties; Scavenging; Skin - cytology; Superoxide dismutase; Superoxide Dismutase - genetics; Time dependence; Toxicity; breast cancer; flow cytometry; human dermal fibroblasts; gene expression; Ferula
• ISSN: 1095-6670; 1099-0461
• DOI: 10.1002/jbt.22402

Introduction
Galbanic acid (GA) is a natural bioactive compound abundantly distributed in Ferula species (Apiaceae), with a wide range of biological functions.
Methods
The present study investigated the anticancer properties of GA in human breast carcinoma MCF‐7 and MDA‐MB‐231 cell lines using MTT (3,4,5‐dimethylthiazol‐2‐yl‐2,5‐diphenyltetrazolium bromide) assay. Further, the antioxidant activity of GA was determined in vitro. The plausible mechanisms of action of GA were further investigated using flow cytometry and gene expression analysis.
Results
Our study indicated that treatment with GA resulted in inhibition of proliferation and induction of apoptosis in MDA‐MB‐231 cells. The obtained results indicated that GA has strong cytotoxicity on MDA‐MB‐231 cells (IC50 = 48.75 µg/mL) compare to MCF‐7 (IC50 = 56.65 µg/mL) and decrease cancer cell viability in the dose‐ and time‐dependent manner. Meanwhile, microscopic examination and flow cytometry analysis confirmed the apoptosis cell death upon treatment with GA. The gene expression analysis revealed that GA could induce apoptosis‐mediated proliferation inhibition in MDA‐MB‐231 cells through upregulation of bax and caspase‐3 and downregulation of bcl2 genes. Besides, the GA exhibited free radical–scavenging activity and enhanced the cellular redox state in human dermal fibroblasts. The elevation of cellular redox status was confirmed by upregulating superoxide dismutase, catalase, and glutathione peroxidase genes.
Conclusion
The results obtained in this study indicated that GA could be considered as a promising anticancer agent in breast cancer therapy and a bioactive antioxidant compound to be used in pharmaceutical and cosmetic industries.