Journal
VIRUSES-BASEL
Volume 14, Issue 9, Pages -Publisher
MDPI
DOI: 10.3390/v14091848
Keywords
schweinfurthin; Merkel cell carcinoma; Merkel cell polyomavirus; small T; PI3K; AKT; MAPK; ERK
Categories
Funding
- National Cancer Institute, National Institutes of Health [T32 CA060395]
- Dale E. and Barbara R. Yingst Merkel Cell Cancer Research Fund
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Merkel cell carcinoma (MCC) is an aggressive form of skin cancer caused by the Merkel cell polyomavirus (MCPyV). A recent study found that schweinfurthin compounds can selectively inhibit MCPyV-infected cancer cell lines and induce apoptosis. This discovery suggests a promising new therapeutic option for virus-induced MCC.
Merkel cell carcinoma (MCC) is a rare but aggressive form of skin cancer predominantly caused by the human Merkel cell polyomavirus (MCPyV). Treatment for MCC includes excision and radiotherapy of local disease, and chemotherapy or immunotherapy for metastatic disease. The schweinfurthin family of natural compounds previously displayed potent and selective growth inhibitory activity against the NCI-60 panel of human-derived cancer cell lines. Here, we investigated the impact of schweinfurthin on human MCC cell lines. Treatment with the schweinfurthin analog, 5 '-methylschweinfurth G (MeSG also known as TTI-3114), impaired metabolic activity through induction of an apoptotic pathway. MeSG also selectively inhibited PI3K/AKT and MAPK/ERK pathways in the MCPyV-positive MCC cell line, MS-1. Interestingly, expression of the MCPyV small T (sT) oncogene selectively sensitizes mouse embryonic fibroblasts to MeSG. These results suggest that the schweinfurthin family of compounds display promising potential as a novel therapeutic option for virus-induced MCCs.
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