Deuterium depleted water effects on survival of lung cancer patients and expression of Kras, Bcl2, and Myc genes in mouse lung

Abstract

Although advances in cancer therapies continue to develop, the shortness of the survival of lung cancer patients is still disappointing. Therefore, finding new adjuvant strategies is within the focus of cancer cure. Based on observations that deuterium depletion inhibits the growth of cancer cell lines and suppresses certain proto-oncogenes, we have conducted a clinical study in 129 patients with small cell and nonsmall cell lung cancers who consumed deuterium-depleted drinking water (DDW) as a nontoxic agent in addition to conventional chemotherapy and radiotherapy. Median survival time (MST) was 25.9 mo in males and 74.1 mo in female patients; the difference between genders was statistically significant (p < 0.05). Median survival of subjects with brain metastasis was 27.1 mo. Cumulative 5-yr survival probabilities were 19%, 52%, and 33% in males, females, and all patients with brain metastasis, respectively. Gene expression analysis in mouse lung indicated that DDW attenuates 7,12-dimethylbenz(a)anthracene (DMBA)-induced expression of Bcl2, Kras, and Myc in females. In conclusion, DDW counteracts the DMBA-induced overexpression of Bcl2, Kras and Myc genes in mouse lung, and it may extend survival of lung cancer patients as a nontoxic anticancer dietary supplement, especially for women with tumors overexpressing cancer-related genes, because MST of DDW-consuming group was 2-4 times longer than it is generally observed in lung cancer patients.

FIG. 1.

Cumulative survival probabilities among the different patient groups in the study. There are significant survival difference observed between genders (A; lines: male —, female —; Wilcoxon and log rank tests, p < 0.05), and between different age groups (panel C; lines: 36–51 years —, 52–58 years —, 59–65 years 66–83 years -••-; according to log rank test only p < 0.05). No significant differences in survival were observed on the basis of stage of the disease, as assessed by Duke's classification system (D; lines: stadium B —, stadium C without brain metastasis —, stadium C with brain metastasis …; Wilcoxon and log rank tests p > 0.05), or presence of brain metastasis (B; lines: with brain metastasis —, without brain metastasis —; Wilcoxon and log rank tests p > 0.05).

FIG. 2.

Expression of lung cancer-related proto-oncogenes in the lung tissue of experimental mice. The values given in ppm on the x-axes represent the concentration of deuterium in the deuterium-depleted drinking water (DDW) (25 ppm) and control drinking water (150 ppm). DMBA: 7,12-dimethylbenz(a)anthracene. Effects of levels of deuterium in drinking water on Kras gene expression in lungs of female and male mice are graphed in panels A and D; effects on Bcl2 expression in lungs of female and male mice are shown in panels B and E, whereas Myc expression in lungs of female and male mice are seen in panels C and F, respectively. There was significant (∗p < 0.05) difference in gene expression observed in DMBA-treated female animals consuming DDW or tap water at all the examined genes. (150 ppm = normal drinking water without DMBA-treatment, 150 ppm + DMBA = normal drinking water with DMBA-treatment, 25 ppm = deuterium-depleted drinking water without DMBA-treatment, 25 ppm + DMBA = deuterium-depleted drinking water with DMBA-treatment).