Abstract

Simple SummaryCancer relapses after chemo-radiotherapies arise from cancer stem cells able to escape cell killing because of their high antioxidants level. The aim of this study was to test the efficacy of ozonized oils to decrease the rate of cancer relapses. In vitro, oils at high ozonide content penetrate inside cancer cells releasing oxygen and reactive oxygen species damaging the thin outer membrane of inactive mitochondria. This event triggers intracellular calcium release and activates apoptosis. In vivo, ozonized oil has been administered by the oral route effectively decreasing blood antioxidants in cancer patients. This approach results in significant increase of survival rate and decrease of relapses in 115 cancer patients (brain, lung, pancreas, colon, skin) undergoing standard radio-chemotherapy regimens during a 4-years follow up. Obtained results indicate that the administration of ozonized oil represents an integrated approach to decrease the risk of radio-chemoresistance and cancer relapses in cancer patients.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.

Highlights

  • Cancer cells differ from normal cells in several aspects, among which the blockage of the mitochondrial function stands out

  • This experiment showed that the amount of ozonide is the key element of the killing effect of ozonized oils against cancer cells

  • high-ozonide ozonized oil (HOO) 1100 was selected for further analyses because of the highest level of cancer cell killing efficacy as compared with the other ozonized oils

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Summary

Introduction

Cancer cells differ from normal cells in several aspects, among which the blockage of the mitochondrial function stands out. The mitochondrial blockage occurring in cancer cells is known as the Warburg effect [1]. Cancer stem cells, which give rise to chemo/radio resistance and relapses, are characterized by a reducing environment, being sensitive to the cytotoxic effects of oxidative damage [2]. Today the increase in oxidative damage represents a possible strategy for cancer therapy [4]. Oxidation is a possible strategy for counteracting cancer progression and relapses. 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.

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