Cannabigerol Induces Autophagic-Cell Death by Inhibiting EGFR-RAS-Pathways in Human Pancreatic Ductal Adenocarcinoma Cell Lines

Laura Zeppa; Cristina Aguzzi; Maria Beatrice Morelli; Oliviero Marinelli; Martina Giangrossi; Margherita Luongo; Consuelo Amantini; Giorgio Santoni; Massimo Nabissi

doi:10.20944/preprints202401.1396.v1

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preprints.org > medicine and pharmacology > oncology and oncogenics > doi: 10.20944/preprints202401.1396.v1

Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Cannabigerol Induces Autophagic-Cell Death by Inhibiting EGFR-RAS-Pathways in Human Pancreatic Ductal Adenocarcinoma Cell Lines

Laura Zeppa

Cristina Aguzzi

Maria Beatrice Morelli

Version 1 : Received: 17 January 2024 / Approved: 18 January 2024 / Online: 18 January 2024 (13:54:21 CET)

A peer-reviewed article of this Preprint also exists.

Zeppa, L.; Aguzzi, C.; Morelli, M.B.; Marinelli, O.; Giangrossi, M.; Luongo, M.; Amantini, C.; Santoni, G.; Nabissi, M. Cannabigerol Induces Autophagic Cell Death by Inhibiting EGFR-RAS Pathways in Human Pancreatic Ductal Adenocarcinoma Cell Lines. Int. J. Mol. Sci. 2024, 25, 2001. Zeppa, L.; Aguzzi, C.; Morelli, M.B.; Marinelli, O.; Giangrossi, M.; Luongo, M.; Amantini, C.; Santoni, G.; Nabissi, M. Cannabigerol Induces Autophagic Cell Death by Inhibiting EGFR-RAS Pathways in Human Pancreatic Ductal Adenocarcinoma Cell Lines. Int. J. Mol. Sci. 2024, 25, 2001.

Abstract

Pancreatic Ductal Adenocarcinoma (PDAC) is the most frequent infiltrating type of pancreatic cancer. The poor prognosis is due to the absence of specific biomarkers, aggressiveness and treatment resistance. PDAC is a deadly malignancy bearing distinct genetic alterations, the most common being those that cause cancer-causing versions of the KRAS gene. Cannabigerol (CBG) is a non-psychomimetic cannabinoid with anti-inflammatory property. Regarding CBG anticancer ef-fect, up to now there are only few evidence in human cancers. We investigated CBG effects on PDAC cell lines, PANC-1 and MIAPaCa-2. It was investigated CBG activity on cell viability, cell death and its effect of EGFR-RAS-associated signalling. Moreover, the potential synergistic effect of CBG in combination with gemcitabine (GEM) and paclitaxel (PTX) was investigated. MTT was applied to investigate CBG effect on PDAC cell lines viability. Annexin-V and Acridine Orange staining followed by cytofluorimetric analysis and Western blot were used to evaluate CBG effect on cell death. Modulation of EGFR-RAS-associated pathways was determined by Western Blot analysis and Milliplex multiplex assay. Moreover, by MTT data and Synergy finder software analysis the effect of the combination of CBG and chemotherapeutic drugs, was determined.

Keywords

cannabigerol; pancreatic cancer; autophagy; chemo-resistance; RAS pathways

Subject

Medicine and Pharmacology, Oncology and Oncogenics

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.

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