Transcriptome analysis of genes associated with breast cancer cell motility in response to Artemisinin treatment

Abstract

BackgroundWell-known anti-malarial drug artemisinin exhibits potent anti-cancerous activities. In-vivo and in-vitro studies showed its anti-tumor and immunomodulatory properties signifying it as a potent drug candidate for study. The studies of mechanisms of cell movement are relevant which can be understood by knowing the involvement of genes in an effect of a drug. Although cytotoxicity and anti-proliferative activity of artemisinin is evident, the genes participating in its anti-migratory and reduced invasive effect are not well studied. The present study reports the alteration in the expression of 84 genes involved in cell motility upon artemisinin treatment in MCF-7 breast cancer cells using pathway focused gene expression PCR array. In addition, the effect of artemisinin on epigenetic modifier HDACs is studied.MethodsWe checked the functional stimulus of artemisinin on cell viability, migration, invasion and apoptosis in breast cancerous cell lines. Using qRT-PCR and western blot, we validated the altered expression of relevant genes associated with proliferation, migration, invasion, apoptosis and mammary gland development.ResultsArtemisinin inhibited cell proliferation of estrogen receptor negative breast cancer cells with fewer efficacies in comparison to estrogen receptor positive ones. At the same time, cell viability and proliferation of normal breast epithelial MCF10A cells was un-affected. Artemisinin strongly inhibited cancer cell migration and invasion. Along with orphan nuclear receptors (ERRα, ERRβ and ERRγ), artemisinin altered the ERα/ERβ/PR/Her expression status of MCF-7 cells. The expression of genes involved in the signaling pathways associated with proliferation, migration, invasion and apoptosis was significantly altered which cooperatively resulted into reduced growth promoting activities of breast cancer cells. Interestingly, artemisinin exhibited inhibitory effect on histone deacetylases (HDACs).ConclusionsUpregulated expression of tumor suppressor genes along with reduced expression of oncogenes significantly associated with growth stimulating signaling pathways in response to artemisinin treatment suggests its efficacy as an effective drug in breast cancer treatment.

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

“…ART inhibits cell proliferation, migration and invasion, and induces apoptosis in human breast cancer MCF-7 cells [193,196], while DHA suppresses cell growth through cell cycle arrest and apoptosis in human hepatocellular carcinoma HepG2 cells and HepG2 xenograft mice [178]. Similarly, ART induces apoptosis in murine mastocytome P815 cells and hamster kidney adenocarcinoma BSR cells, and inhibits tumor growth in P815 xenograft mice [177].…”

“…In the past decades, studies have been focused on studying the anti-cancer mechanisms of ARTs, but there are contentions. ARTs inhibit cancer cell proliferation mainly by the induction of apoptosis through mitochondrialdependent pathways [196,205,206]. ART mediates the release of cytochrome c and caspase-9 cleavage, leading to increased apoptosis in human breast cancer MCF-7 cells [196].…”

“…ARTs inhibit cancer cell proliferation mainly by the induction of apoptosis through mitochondrialdependent pathways [196,205,206]. ART mediates the release of cytochrome c and caspase-9 cleavage, leading to increased apoptosis in human breast cancer MCF-7 cells [196]. DHA induces apoptosis through Bcl-2 downregulation in human cervical cancer HeLa and Caski cells [205], and via Bim-dependent intrinsic pathway in human hepatocellular carcinoma HepG2 and Huh7 cells [206].…”

“…DHA induces apoptosis through Bcl-2 downregulation in human cervical cancer HeLa and Caski cells [205], and via Bim-dependent intrinsic pathway in human hepatocellular carcinoma HepG2 and Huh7 cells [206]. Interestingly, ART is demonstrated to be an inhibitor of anti-cancer target, histone deacetylases (HDAC) [196]. In addition, another mechanism of killing tumor cells by ARTs is iron-dependent cell death called ferroptosis, a new form of cell death, so ferroptosis becomes an attractive strategy for cancer treatment [183,207].…”

<p>Fourier Transform Infrared Spectroscopy Monitoring of Dihydroartemisinin-Induced Growth Inhibition in Ovarian Cancer Cells and Normal Ovarian Surface Epithelial Cells</p>

“…9,10 Previous studies have reported extensive examinations of ARS and its analogs in ovarian, prostate, pancreatic, breast and liver cancers or cells and showed little cytotoxicity and strong synergistic anticancer effects when combined with conventional chemotherapeutic agents. 8,[11][12][13][14] In this study, we investigated the antitumor effects of DHA, one of the analogs of ARS, on the cell proliferation and inhibition of ovarian cancer cells. We also examined the alterations in cellular molecules such as proteins, lipids and nucleic acids using Fourier transform infrared (FTIR) spectroscopy after DHA exposure.…”