Therapeutic Potential of 5′-Methylschweinfurthin G in Merkel Cell Polyomavirus-Positive Merkel Cell Carcinoma

Emily J. Koubek, Jillian S. Weissenrieder, Luz E. Ortiz, Nnenna Nwogu, Alexander M. Pham, J. Dylan Weissenkampen, Jessie L. Reed, Jeffrey D. Neighbors, Raymond J. Hohl, Hyun Jin Kwun

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number1848
JournalViruses
Volume14
Issue number9
DOIs
StatePublished - Sep 2022

All Science Journal Classification (ASJC) codes

  • Infectious Diseases
  • Virology

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