Version 1
: Received: 29 February 2024 / Approved: 29 February 2024 / Online: 29 February 2024 (10:49:18 CET)
How to cite:
Serala, K.; Bai, J.; Prince, S. Pyrvinium Pamoate Enhances the Anti-cancer Activities of Gemcitabine in Pancreatic Cancer. Preprints2024, 2024021726. https://doi.org/10.20944/preprints202402.1726.v1
Serala, K.; Bai, J.; Prince, S. Pyrvinium Pamoate Enhances the Anti-cancer Activities of Gemcitabine in Pancreatic Cancer. Preprints 2024, 2024021726. https://doi.org/10.20944/preprints202402.1726.v1
Serala, K.; Bai, J.; Prince, S. Pyrvinium Pamoate Enhances the Anti-cancer Activities of Gemcitabine in Pancreatic Cancer. Preprints2024, 2024021726. https://doi.org/10.20944/preprints202402.1726.v1
APA Style
Serala, K., Bai, J., & Prince, S. (2024). Pyrvinium Pamoate Enhances the Anti-cancer Activities of Gemcitabine in Pancreatic Cancer. Preprints. https://doi.org/10.20944/preprints202402.1726.v1
Chicago/Turabian Style
Serala, K., Jinming Bai and Sharon Prince. 2024 "Pyrvinium Pamoate Enhances the Anti-cancer Activities of Gemcitabine in Pancreatic Cancer" Preprints. https://doi.org/10.20944/preprints202402.1726.v1
Abstract
Pancreatic cancer is an intractable disease with the worst prognosis of all cancers. The currently used treatment regimens do not significantly impact patient survival, and therefore, effective treatment strategies are urgently needed. Drug repurposing, which identifies new indications for existing and approved drugs, has proven to be a promising approach to anti-cancer drug discovery. Indeed the antihelmintic drug, pyrvinium pamoate has shown promise as an anti-pancreatic cancer drug, but to date, the inhibition of mitochondrial function is the only mechanism of action described in pancreatic cancer. This study showed, using pancreatic cancer 2D cell cultures and 3D spheroids, that pyrvinium pamoate exhibited short- and long-term cytotoxicity, inhibited epithelial-to-mesenchymal transition and cell invasion and migration. Mechanistically, pyrvinium pamoate induced DNA damage, inhibited the PI3K/AKT cell survival pathway, and triggered cell cycle arrests, as well as apoptotic and autophagic cell death. Importantly, pyrvinium pamoate acted synergistically with the first-line drug, gemcitabine in 2D and 3D pancreatic cancer cell culture models. This study provided evidence that pyrvinium pamoate is effective as a single agent and in combination with gemcitabine for the treatment of pancreatic cancer.
Keywords
pyrvinium pamoate; pancreatic cancer; drug repurposing; drug combination; gemcitabine
Subject
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
