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Cannabidiol and Oxygen-Ozone Combination Induce Cytotoxicity in Human Pancreatic Ductal Adenocarcinoma Cell Lines

1
“Maria Guarino” Foundation—AMOR No Profit Association, 80078 Pozzuoli, Italy
2
School of Pharmacy, University of Camerino, 62032 Camerino (MC), Italy
3
School of Bioscience and Veterinary Medicine, University of Camerino, 62032 Camerino (MC), Italy
4
Department of Radiotherapy, Ecomedica Empoli, 50053 Empoli FI, Italy
5
Integrative Therapy Discovery Lab, University of Camerino, 62032 Camerino (MC), Italy
*
Author to whom correspondence should be addressed.
These authors have equally contributed to this work.
Cancers 2020, 12(10), 2774; https://doi.org/10.3390/cancers12102774
Received: 10 June 2020 / Revised: 10 September 2020 / Accepted: 24 September 2020 / Published: 27 September 2020
Pancreatic cancer (PC) is related to lifestyle risks, chronic inflammation, and germline mutations. Surgical resection and adjuvant chemotherapy are the main therapeutic strategies but are less effective in patients with high-grade tumors. Oxygen-ozone (O2/O3) therapy is an emerging alternative tool for the treatment of several clinical disorders. The advantages of using cannabinoids have been evaluated in several human cancers. Regarding PC, activation of cannabinoid receptors was found to induce PC cell apoptosis without affecting the normal pancreas cells. Herein, we evaluate the anticancer effect of cannabidiol (CBD) and O2/O3, alone or in combination, on two human pancreatic ductal adenocarcinoma (PDAC) cell lines, PANC-1 and MiaPaCa-2, examining expression profiles of 92 pancreatic adenocarcinoma associated genes, cytotoxicity, migration properties, and cell death. Finally, we assess the combination effects with gemcitabine and paclitaxel. Summarizing, for the first time the antitumoral effect of combined therapy with CBD and oxygen-ozone therapy in PDAC is evidenced.
Pancreatic cancer (PC) is related to lifestyle risks, chronic inflammation, and germline mutations in BRCA1/2, ATM, MLH1, TP53, or CDKN2A. Surgical resection and adjuvant chemotherapy are the main therapeutic strategies but are less effective in patients with high-grade tumors. Oxygen-ozone (O2/O3) therapy is an emerging alternative tool for the treatment of several clinical disorders. O2/O3 therapy has been found to ameliorate mechanisms promoting chronic pain and inflammation, including hypoxia, inflammatory mediators, and infection. The advantages of using cannabinoids have been evaluated in vitro and in vivo models of several human cancers. Regarding PDAC, activation of cannabinoid receptors was found to induce pancreatic cancer cell apoptosis without affecting the normal pancreas cells. In a murine model of PDAC, a combination of cannabidiol (CBD) and gemcitabine increased survival length by nearly three times. Herein, we evaluate the anticancer effect of CBD and O2/O3, alone or in combination, on two human PDAC cell lines, PANC-1 and MiaPaCa-2, examining expression profiles of 92 pancreatic adenocarcinoma associated genes, cytotoxicity, migration properties, and cell death. Finally, we assess the combination effects with gemcitabine and paclitaxel. Summarizing, for the first time the antitumoral effect of combined therapy with CBD and oxygen-ozone therapy in PDAC is evidenced. View Full-Text
Keywords: cannabidiol; oxygen-ozone; pancreatic cancer; cytotoxicity; migration; chemo-resistance; PDAC gene profile cannabidiol; oxygen-ozone; pancreatic cancer; cytotoxicity; migration; chemo-resistance; PDAC gene profile
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MDPI and ACS Style

Luongo, M.; Marinelli, O.; Zeppa, L.; Aguzzi, C.; Morelli, M.B.; Amantini, C.; Frassineti, A.; di Costanzo, M.; Fanelli, A.; Santoni, G.; Nabissi, M. Cannabidiol and Oxygen-Ozone Combination Induce Cytotoxicity in Human Pancreatic Ductal Adenocarcinoma Cell Lines. Cancers 2020, 12, 2774. https://doi.org/10.3390/cancers12102774

AMA Style

Luongo M, Marinelli O, Zeppa L, Aguzzi C, Morelli MB, Amantini C, Frassineti A, di Costanzo M, Fanelli A, Santoni G, Nabissi M. Cannabidiol and Oxygen-Ozone Combination Induce Cytotoxicity in Human Pancreatic Ductal Adenocarcinoma Cell Lines. Cancers. 2020; 12(10):2774. https://doi.org/10.3390/cancers12102774

Chicago/Turabian Style

Luongo, Margherita, Oliviero Marinelli, Laura Zeppa, Cristina Aguzzi, Maria B. Morelli, Consuelo Amantini, Andrea Frassineti, Marianne di Costanzo, Alessandro Fanelli, Giorgio Santoni, and Massimo Nabissi. 2020. "Cannabidiol and Oxygen-Ozone Combination Induce Cytotoxicity in Human Pancreatic Ductal Adenocarcinoma Cell Lines" Cancers 12, no. 10: 2774. https://doi.org/10.3390/cancers12102774

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