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

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)...

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Bibliographic Details
Published in:Cancers 2020-10, Vol.12 (10), p.2774
Main Authors: Luongo, Margherita, Marinelli, Oliviero, Zeppa, Laura, Aguzzi, Cristina, Morelli, Maria Beatrice, Amantini, Consuelo, Frassineti, Andrea, di Costanzo, Marianne, Fanelli, Alessandro, Santoni, Giorgio, Nabissi, Massimo
Format: Article
Language:English
Subjects:
Adenocarcinoma
Animal models
Apoptosis
BRCA1 protein
Cancer therapies
Cannabidiol
Cannabinoid receptors
Cannabinoids
Cell death
Cell migration
Chemotherapy
Chronic infection
Cytotoxicity
Drug therapy
Gemcitabine
Hypoxia
Inflammation
Kinases
MLH1 protein
Mutation
Oxygen
Ozone
p53 Protein
Paclitaxel
Pancreatic cancer
Patient outcomes
Patients
Tumor cell lines
Tumors
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Summary: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.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers12102774