Use of ozonated water as a new therapeutic approach to solve current concerns around antitumor treatment

Tumor hypoxia is a severe problem affecting tumor therapy because it reduces the sensitivity of chemotherapy and radiation therapy. Ozone has been known to improve peripheral blood perfusion and oxygen partial pressure. The effect of ozonated water on tumor hypoxia, alone and in combination with an antitumor drug was studied in the present study. Following intraperitoneal administration of ozonated water to colon-26-bearing mice, the Hoechst 33342-positive area and the intratumoral oxygen partial pressure was significantly increased. The tumor growth rate was more suppressed when ozonated water was combined with cisplatin (CDDP) compared with CDDP treatment alone. The number of Ki-67-positive cells significantly decreased, whereas the number of TUNEL-positive cells significantly increased. The present study showed that ozonated water increased intratumoral blood perfusion and improved tumor hypoxia. In addition, ozonated water increased the therapeutic effect of CDDP. These findings, as well as previous reports, suggest that tumor growth is suppressed after treatment with ozonated water as the amount of CDDP reaching the tumor is increased when the intratumoral blood perfusion is increased due to the ozonated water. Thus, the administration of ozonated water may be a new therapeutic approach to solve current concerns regarding antitumor treatment.

[1]  Takuro Mori,et al.  The Safety and Anti-Tumor Effects of Ozonated Water in Vivo , 2015, International journal of molecular sciences.

[2]  T. Osaki,et al.  Systemic and local injections of lupeol inhibit tumor growth in a melanoma-bearing mouse model. , 2013, Biomedical reports.

[3]  Colin J. Daniel,et al.  Overcoming hypoxia-induced apoptotic resistance through combinatorial inhibition of GSK-3β and CDK1. , 2011, Cancer research.

[4]  M. Celeste Simon,et al.  The impact of O2 availability on human cancer , 2008, Nature Reviews Cancer.

[5]  H. Shimokawa,et al.  Abstract 3629: Crucial Role of Nitric Oxide Synthases System in Endothelium-Dependent Hyperpolarization in Mice , 2008 .

[6]  E. Kantorovich,et al.  Ozone therapy in medicine and dentistry. , 2008, The journal of contemporary dental practice.

[7]  S. Menéndez,et al.  Ozone/oxygen mixture modifies the subcellular redistribution of Bax protein in renal tissue from rats treated with cisplatin. , 2006, Archives of medical research.

[8]  Z. Zamora,et al.  Reversion by ozone treatment of acute nephrotoxicity induced by cisplatin in rats. , 2004, Mediators of inflammation.

[9]  M. Lloret,et al.  Adjuvant Ozonetherapy in Advanced Head and Neck Tumors: A Comparative Study , 2004, Evidence-based complementary and alternative medicine : eCAM.

[10]  J. Brown,et al.  Exploiting tumour hypoxia in cancer treatment , 2004, Nature Reviews Cancer.

[11]  M. Lloret,et al.  Ozone Therapy for Tumor Oxygenation: a Pilot Study , 2004, Evidence-based complementary and alternative medicine : eCAM.

[12]  Crispin J. Miller,et al.  Hypoxia-Mediated Down-Regulation of Bid and Bax in Tumors Occurs via Hypoxia-Inducible Factor 1-Dependent and -Independent Mechanisms and Contributes to Drug Resistance , 2004, Molecular and Cellular Biology.

[13]  S. Menéndez,et al.  Protection by ozone preconditioning is mediated by the antioxidant system in cisplatin-induced nephrotoxicity in rats. , 2004, Mediators of inflammation.

[14]  G. Semenza Targeting HIF-1 for cancer therapy , 2003, Nature Reviews Cancer.

[15]  S. Rilling,et al.  The Use of Ozone in Medicine , 2002 .

[16]  J. Essigmann,et al.  Mechanisms of resistance to cisplatin. , 2001, Mutation research.

[17]  Chi V. Dang,et al.  Hypoxia Inhibits G1/S Transition through Regulation of p27 Expression* , 2001, The Journal of Biological Chemistry.

[18]  David E. Housman,et al.  Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours , 1996, Nature.

[19]  O. Amellem,et al.  Regulation of cell proliferation under extreme and moderate hypoxia: the role of pyrimidine (deoxy)nucleotides. , 1994, British Journal of Cancer.

[20]  B. Teicher Hypoxia and drug resistance , 1994, Cancer and Metastasis Reviews.

[21]  B. Brown,et al.  The effect of cis-diamminedichloroplatinum (II) on cultured human lymphoma cells and its therapeutic implications. , 1973, Cancer research.

[22]  V. Bocci,et al.  The Use of Ozone in Medicine , 2018 .

[23]  R. Hill,et al.  The tumor microenvironment and metastatic disease , 2008, Clinical & Experimental Metastasis.