Antimalaria Drug May Inhibit Virus-Positive Merkel Cell Carcinoma Growth
Posted: Tuesday, July 28, 2020
Artesunate appears to induce nonapoptotic cell death of Merkel cell polyomavirus (MCPyV)-positive Merkel cell carcinoma cells in vitro, according to a recent study conducted by Roland Houben, PhD, of the University Hospital Würzburg, Germany, and colleagues. The results, which were published in Cancers, revealed this antimalaria drug also seemed to inhibit tumor growth in vivo and thus may prove to be effective in clinical practice.
“In about 80% of [Merkel cell carcinomas], there is an association with MCPyV; the expression of viral T antigens is crucial for growth of virus-positive tumor cells,” the investigators remarked. “Since artesunate has been reported to possess additional antitumor as well as antiviral activity, we sought to evaluate preclinically the effect of artesunate on Merkel cell carcinoma.”
Five-week-old female NOD.CB17/Prkdcscid mice were injected with a suspension of MKL-1 or WaGa tumor cells and subsequently divided into experimental and control groups. The mice received daily intraperitoneal injections of dimethyl sulfoxide (DMSO) in phosphate-buffered saline, with or without artesunate. Cell culture was performed using the MCPyV-positive Merkel cell carcinoma cell lines MKL-1, MKL-2, MS-1, WaGa, and PeTa. Additionally, a series of assays were performed to analyze the antitumor mechanisms associated with artesunate therapy.
An MTS assay revealed reduced signals of the WaGa and MKL-1 cell lines, indicating artesunate inhibited both growth and survival of MCPyV-positive tumors in vitro. According to the results of an immunoblot analysis, large T-cell antigen expression decreased in cells treated with artesunate after a 3-day incubation period. Artesunate exhibited stronger cytotoxic effects than short hairpin RNA-mediated T-antigen knockdown. Because several known ferroptosis inhibitors reduced artesunate-induced cell death, the investigators proposed artesunate may trigger ferroptosis by dysregulating lipid metabolism and autophagy. In mice, malignant growth was significantly reduced in both MKL-1 (P < .001) and WaGa (P < .0305) tumors after artesunate treatment.
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