Efficacy of High-Ozonide Oil in Prevention of Cancer Relapses Mechanisms and Clinical Evidence

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2022 Mar 10

PMID 35267482

Authors

Alberto Izzotti

Enzo Fracchia

Camillo Rosano

Antonio Comite

Liliana Belgioia

Salvatore Sciacca

Zumama Khalid

Matteo Congiu

Cristina Colarossi

Giusi Blanco

Antonio Santoro

Massimo Chiara

Alessandra Pulliero

Affiliations

Soon will be listed here.

Abstract

Background: Cancer tissue is characterized by low oxygen availability triggering neo angiogenesis and metastatisation. Accordingly, oxidation is a possible strategy for counteracting cancer progression and relapses. Previous studies used ozone gas, administered by invasive methods, both in experimental animals and clinical studies, transiently decreasing cancer growth. This study evaluated the effect of ozonized oils (administered either topically or orally) on cancer, exploring triggered molecular mechanisms.

Methods: In vitro, in lung and glioblastoma cancer cells, ozonized oils having a high ozonide content suppressed cancer cell viability by triggering mitochondrial damage, intracellular calcium release, and apoptosis. In vivo, a total of 115 cancer patients (age 58 ± 14 years; 44 males, 71 females) were treated with ozonized oil as complementary therapy in addition to standard chemo/radio therapeutic regimens for up to 4 years.

Results: Cancer diagnoses were brain glioblastoma, pancreas adenocarcinoma, skin epithelioma, lung cancer (small and non-small cell lung cancer), colon adenocarcinoma, breast cancer, prostate adenocarcinoma. Survival rate was significantly improved in cancer patients receiving HOO as integrative therapy as compared with those receiving standard treatment only.

Conclusions: These results indicate that ozonized oils at high ozonide may represent an innovation in complementary cancer therapy worthy of further clinical studies.

Citing Articles

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Oxidative Drugs and microRNA: New Opportunities for Cancer Prevention.

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References

Colla R, Izzotti A, Ciucis C, Fenoglio D, Ravera S, Speciale A . Glutathione-mediated antioxidant response and aerobic metabolism: two crucial factors involved in determining the multi-drug resistance of high-risk neuroblastoma. Oncotarget. 2016; 7(43):70715-70737. PMC: 5342585. DOI: 10.18632/oncotarget.12209. View

Ngo H, Kim D, Cha Y, Na H, Surh Y . Nrf2 Mutagenic Activation Drives Hepatocarcinogenesis. Cancer Res. 2017; 77(18):4797-4808. DOI: 10.1158/0008-5472.CAN-16-3538. View

Serena B, Primiterra M, Catalani S, Finco A, Canestrari F, Cornelli U . Performance evaluation of the innovative PAT test, comparison with the common BAP test and influence of interferences on the evaluation of the plasma antioxidant capacity. Clin Lab. 2013; 59(9-10):1091-7. View

Zhou D, Shao L, Spitz D . Reactive oxygen species in normal and tumor stem cells. Adv Cancer Res. 2014; 122:1-67. PMC: 4207279. DOI: 10.1016/B978-0-12-420117-0.00001-3. View

Perillo B, Di Donato M, Pezone A, Di Zazzo E, Giovannelli P, Galasso G . ROS in cancer therapy: the bright side of the moon. Exp Mol Med. 2020; 52(2):192-203. PMC: 7062874. DOI: 10.1038/s12276-020-0384-2. View

Zhong H, Xiao M, Zarkovic K, Zhu M, Sa R, Lu J . Mitochondrial control of apoptosis through modulation of cardiolipin oxidation in hepatocellular carcinoma: A novel link between oxidative stress and cancer. Free Radic Biol Med. 2016; 102:67-76. DOI: 10.1016/j.freeradbiomed.2016.10.494. View

Izzotti A, Fracchia E, Au W, Colombo M, Pfeffer U, Emionite L . Prevention of Covid-19 Infection and Related Complications by Ozonized Oils. J Pers Med. 2021; 11(3). PMC: 8004285. DOI: 10.3390/jpm11030226. View

Wani J, Majid S, Khan A, Arafah A, Ahmad A, Jan B . Clinico-Pathological Importance of miR-146a in Lung Cancer. Diagnostics (Basel). 2021; 11(2). PMC: 7916675. DOI: 10.3390/diagnostics11020274. View

Liu J, Wang Z . Increased Oxidative Stress as a Selective Anticancer Therapy. Oxid Med Cell Longev. 2015; 2015:294303. PMC: 4529973. DOI: 10.1155/2015/294303. View

10.

Brooks B, Brooks 3rd C, MacKerell Jr A, Nilsson L, Petrella R, Roux B . CHARMM: the biomolecular simulation program. J Comput Chem. 2009; 30(10):1545-614. PMC: 2810661. DOI: 10.1002/jcc.21287. View

11.

Marengo B, Monti P, Miele M, Menichini P, Ottaggio L, Foggetti G . Etoposide-resistance in a neuroblastoma model cell line is associated with 13q14.3 mono-allelic deletion and miRNA-15a/16-1 down-regulation. Sci Rep. 2018; 8(1):13762. PMC: 6137223. DOI: 10.1038/s41598-018-32195-7. View

12.

Lin Y . MicroRNA Networks Modulate Oxidative Stress in Cancer. Int J Mol Sci. 2019; 20(18). PMC: 6769781. DOI: 10.3390/ijms20184497. View

13.

Radzimierska-Kazmierczak M, Smigielski K, Sikora M, Nowak A, Plucinska A, Kunicka-Styczynska A . Olive Oil with Ozone-Modified Properties and Its Application. Molecules. 2021; 26(11). PMC: 8196576. DOI: 10.3390/molecules26113074. View

14.

Westaby D, Jimenez-Vacas J, Padilha A, Varkaris A, Balk S, de Bono J . Targeting the Intrinsic Apoptosis Pathway: A Window of Opportunity for Prostate Cancer. Cancers (Basel). 2022; 14(1). PMC: 8750516. DOI: 10.3390/cancers14010051. View

15.

Kansanen E, Kuosmanen S, Leinonen H, Levonen A . The Keap1-Nrf2 pathway: Mechanisms of activation and dysregulation in cancer. Redox Biol. 2013; 1:45-9. PMC: 3757665. DOI: 10.1016/j.redox.2012.10.001. View

16.

Geretto M, Pulliero A, Rosano C, Zhabayeva D, Bersimbaev R, Izzotti A . Resistance to cancer chemotherapeutic drugs is determined by pivotal microRNA regulators. Am J Cancer Res. 2017; 7(6):1350-1371. PMC: 5489783. View

17.

Song N, Kim D, Kim E, Na H, Kim N, Suh Y . Multidrug resistance-associated protein 1 mediates 15-deoxy-Δ(12,14)-prostaglandin J2-induced expression of glutamate cysteine ligase expression via Nrf2 signaling in human breast cancer cells. Chem Res Toxicol. 2011; 24(8):1231-41. DOI: 10.1021/tx200090n. View

18.

Pulliero A, Wu Y, Fenoglio D, Parodi A, Romani M, Soares C . Nanoparticles increase the efficacy of cancer chemopreventive agents in cells exposed to cigarette smoke condensate. Carcinogenesis. 2015; 36(3):368-77. DOI: 10.1093/carcin/bgv008. View

19.

Pennacchietti S, Michieli P, Galluzzo M, Mazzone M, Giordano S, Comoglio P . Hypoxia promotes invasive growth by transcriptional activation of the met protooncogene. Cancer Cell. 2003; 3(4):347-61. DOI: 10.1016/s1535-6108(03)00085-0. View

20.

Iannitti T, Rottigni V, Palmieri B . Role of free radicals and antioxidant defences in oral cavity-related pathologies. J Oral Pathol Med. 2012; 41(9):649-61. DOI: 10.1111/j.1600-0714.2012.01143.x. View