Computational and In Vitro Approaches to Elucidate the Anti-cancer Effects of Arnica montana in Hormone-Dependent Breast Cancer

Abstract

Background Breast cancer is the most common cancer in women worldwide. Use of homeopathic medicines for the treatment of cancers has increased in the last several years. Arnica montana is an anti-inflammatory homeopathic medicine used in traumatic conditions and because of this property we performed investigations for its potential as a chemotherapeutic agent against breast cancer. Methods An ethanolic extract of Arnica montana (mother tincture, MT), prepared according to the Homoeopathic Pharmacopoeia of India, was characterized by gas chromatography–mass spectroscopy (GC–MS), followed by computational (in silico) analysis using molecular docking, to identify specific compounds that can bind and modulate the activity of key proteins involved in breast cancer survival and progression. To validate the in silico findings, in a controlled experiment breast cancer cells (MCF7) were treated in vitro with Arnica montana and the cytotoxic effects assessed by flowcytometry, fluorescence microscopy, scratch assay, clonogenic potential and gene expression analysis. Results Phytochemical characterization of ethanolic extract of Arn MT by GC–MS allowed identification of several compounds. Caryophyllene oxide and 7-hydroxycadalene were selected for molecular docking studies, based on their potential drug-like properties. These compounds displayed selective binding affinity to some of the recognized target proteins of breast cancer, which included estrogen receptor alpha (ERα), progesterone receptor (PR), epidermal growth factor receptor (EGFR), mTOR (mechanistic target of rapamycin) and E-cadherin. In vitro studies revealed induction of apoptosis in MCF7 cells following treatment with Arn MT. Furthermore, treatment with Arn MT revealed its ability to inhibit migration and colony forming abilities of the cancer cells. Conclusion Considering the apoptotic and anti-migratory effects of Arnica montana in breast cancer cells in vitro, there is a need for this medicine to be further validated in an in vivo model.

Overcoming the Challenges of Phytochemicals in Triple Negative Breast Cancer Therapy: The Path Forward

“…Molecular docking studies and simulations have been used to study the interaction between EGFR and a multitude of phytochemicals. These include ethanol-soluble phytochemicals from Arnica montana such as caryophyllene oxide and hydroxycadalene c [ 59 ], furanocoumarin [ 60 ] and PH-1 (4-methyl-5-oxo-tetrahydrofuran-3-yl acetate), and PH-2 (methyl 4-hydroxy-3-methoxybenzoate) from Polygonum hydropiper [ 61 ]. All of these compounds were found to dock with the EGFR receptor with high affinity.…”

Stages of Development and Solvents Determine the Anticancer Potential of Mountain Arnica (Arnica montana L.) Inflorescence Extracts

“…It cannot be excluded that hydrophilic compounds, as in the case of other medicinal plants [32], may have an impact on biological activity. The A. montana inflorescence is characterized by high concentrations of quercetin, and the antitumor activity of this metabolite has been presented many times [47][48][49][50][51]. Therefore, the role of this component and of other hydrophilic constituents in the biological activity of aqueous extracts is very probable.…”