Verticillin A-Loaded Surgical Buttresses Prevent Local Pancreatic Cancer Recurrence in a Murine Model

The fungal metabolite verticillin A is a potent and selective histone methyltransferase inhibitor. It regulates apoptosis, the cell cycle, and stress response, and displays potent activity in the suppression of tumor cell growth in several different in vivo models. Verticillin A sensitizes pancreatic cancer cells to anti-PD-1 immunotherapy by regulating PD-L1 expression. However, as with many natural products, delivery and systemic toxicity are challenges that must be overcome to advance their use as a chemotherapeutic. To both reduce systemic toxicity and improve delivery, we report a verticillin A-loaded surgical buttress, which is well-tolerated at a dose as high as 40 mg/kg. In contrast, free verticillin A administered systemically results in toxicity at a dose of 3 mg/kg. The verticillin A-loaded buttress suppresses tumor recurrence in vivo in a safe and dose-dependent manner against a highly aggressive and metastatic model of pancreatic cancer.

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Publication Details

Journal
Molecular Pharmaceutics
Published
2025-01-27
DOI
https://doi.org/10.1021/acs.molpharmaceut.4c00589
Citations
2
Primary Topic
Pancreatic and Hepatic Oncology Research
Type
article
Field-Weighted Citation Impact
2.09

Funders

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article

Verticillin A-Loaded Surgical Buttresses Prevent Local Pancreatic Cancer Recurrence in a Murine Model

Mark W. Grinstaff, Nicholas H. Oberlies, Kebin Liu, Cedric J. Pearce et al.
2 citations
Molecular Pharmaceutics
Pancreatic and Hepatic Oncology Research
2.09
article

Verticillin A-Loaded Surgical Buttresses Prevent Local Pancreatic Cancer Recurrence in a Murine Model

Mark W. Grinstaff, Nicholas H. Oberlies, Kebin Liu, Cedric J. Pearce, Zeinab Y. Al Subeh, Herma C. Pierre, Aaron H. Colby
article en
2 citations

Abstract

The fungal metabolite verticillin A is a potent and selective histone methyltransferase inhibitor. It regulates apoptosis, the cell cycle, and stress response, and displays potent activity in the suppression of tumor cell growth in several different in vivo models. Verticillin A sensitizes pancreatic cancer cells to anti-PD-1 immunotherapy by regulating PD-L1 expression. However, as with many natural products, delivery and systemic toxicity are challenges that must be overcome to advance their use as a chemotherapeutic. To both reduce systemic toxicity and improve delivery, we report a verticillin A-loaded surgical buttress, which is well-tolerated at a dose as high as 40 mg/kg. In contrast, free verticillin A administered systemically results in toxicity at a dose of 3 mg/kg. The verticillin A-loaded buttress suppresses tumor recurrence in vivo in a safe and dose-dependent manner against a highly aggressive and metastatic model of pancreatic cancer.

Molecular PharmaceuticsVol. 22(3)
Boston University (US), Jordan University of Science and Technology (JO), University of North Carolina at Greensboro (US), Augusta University (US), Charlie Norwood VA Medical Center (US), National Cancer Center of Georgia (GE), Mycosynthetix (United States) (US), Vion Pharmaceuticals (United States) (US)
Small Business Innovation Research, National Institutes of Health, University of North Carolina at Greensboro, National Cancer Institute, National Center for Complementary and Integrative Health
Good health and well-being
Openalex Percentile: Top 14%
Pancreatic and Hepatic Oncology Research
2.09
DOIOpen Access PDFOpenAlex
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