Altered deoxyribonuclease activity in cancer cells and its role in non toxic adjuvant cancer therapy with mixed vitamins C and K3

The alterations of deoxyribonuclease DNase activity in cancer cells were the basis of the utilization of mixed vitamins C and K3 in a nontoxic, adjuvant cancer therapy. In order to localize exactly the altered activities of DNase in cancer cells, histochemical methods were utilized. The deficiency of alkaline and acid DNase activity appeared to be characteristic for non-necrotic cells of malignant human and animal tumors. This enzymatic deficiency appeared in experimental carcinogenesis before the phenotypic signs of malignancy. Tumor promoters directly reduced the activity of both DNases. The incidence of spontaneous malignant human and animal tumors appeared to be inversely proportional to the intensity of the activity of both DNases in normal cells and tissues from which these tumors were derived. The fact that alkaline and acid DNase activity was reactivated during the spontaneous and therapeutically induced necrosis of cancer cells suggests that this enzymatic deficiency of DNase activity in cancer cells was due to the action of specific inhibitors of DNases. Characteristic variations of serum alkaline DNase activity in positive responders to therapy, examined in more than 800 cancer-bearing patients, may be the basis for the development of a useful test for therapeutic prognosis and for monitoring of cancer bearing patients. Acid DNase was selectively reactivated in malignant tumor cells by vitamin C (sodium ascorbate), whereas alkaline DNase was reactivated by vitamin K3. Joint vitamin C and K3 administration produced in vitro and in vivo tumor growth inhibition, potentiation and sensitization of chemo- and/or radiotherapy and a decrease in the number of metastases in animals with experimental tumors. Joint vitamin C and K3 administration may be considered as a possible new, non-toxic, adjuvant cancer therapy, which can be easily introduced into the classic protocols of clinical cancer therapy without any supplementary risk for patients

The Relation between the histochemical activity of nucleases and neoplasms in rat and man

Thèse d'agrégation de l'enseignement supérieur (Faculté de médecine) -- UCL, 197

Possible adjuvant cancer therapy by two prebiotics--inulin or oligofructose.

Dietary treatment with inulin or oligofructose incorporated in the basal diet for experimental animals: (I) reduced the incidence of mammary tumors induced in Sprague-Dawley rats by methylnitrosourea; (II) inhibited the growth of transplantable malignant tumors in mice; (III) decreased the incidence of lung metastases of a malignant tumor implanted intramuscularily in mice. (IV) Moroever, besides such cancer risk reduction effects, dietary treatment with inulin or oligofructose significantly potentiated the effects of subtherapeutic doses of six cytotoxic drugs commonly utilized in human cancer treatment. (V) The same prebiotics potentiated the effects of radiotherapy on solid form of TLT tumors to a statistically very high level. Such dietary treatment, with the inulin or oligofructose potentiating the effects of cancer therapy, might be introduced into classic protocols of human cancer treatment as a new, non-toxic and easily applicable adjuvant cancer therapy without any additional risk to patients

Non-toxic potentiation of cancer radiotherapy by dietary oligofructose or inulin

Non-toxic, dietary treatment with oligofructose or inulin clearly inhibited the growth of a transplantable mouse liver tumor (TLT) and potentiated its chemotherapy. Thus, it appeared interesting to investigate the possible radiotherapy-potentiating effects of the same dietary treatment. Dietary treatment with 15% oligofructose or inulin incorporated in the basal diet was started four weeks before intramuscular transplantation of TLT tumor cells into young adult male mice of the NMRI strain and was continued until the end of the experiment. When the tumors reached approximately 1000 mm3 they were irradiated with a single X-ray dose of 5 to 20 Gy. Tumor dimensions were measured twice weekly and their mean volume per group of mice was compared to the control groups fed the basal diet. This non-toxic dietary treatment with oligofructose or inulin potentiated the effects of radiotherapy at an optimal dose of 10 Gy to a statistically very highly significant (p < 0.0001) level. They were similar for oligofructose and inulin. The introduction of such non-toxic adjuvant treatment potentiating the effect of cancer radiotherapy in classical protocols of human cancer treatment appears to be possible and without any additional risk for the patients

Non-toxic sensitization of cancer chemotherapy by combined vitamin C and K3 pretreatment in a mouse tumor resistant to oncovin.

The effects of combined vitamin C and K3 i.p. injected 3 hours before i.p. administration of single dose of oncovin, to which the ascites liver tumor in mouse (T.L.T.) was completely resistant, were investigated. This pretreatment sensitized the tumor resistant to oncovin, whereas a separate pretreatment with vitamin C or K3 alone was without any effect. This tumor sensitization to the chemotherapy was completely suppressed by catalase pretreatment, thus indicating that hydrogen peroxide generation with subsequent oxidative stress and its consequences may be involved here. Since this sensitization was without any increased general and organ toxicity, its possible introduction into classical protocols of human cancer treatment would be without any supplementary risk

Inulin/oligofructose and anticancer therapy.

The results of our investigations indicate that dietary treatment with inulin or oligofructose incorporated in the basal diet for experimental animals: (i) reduced the incidence of mammary tumors induced in Sprague-Dawley rats by methylnitrosourea; (ii) inhibited the growth of transplantable malignant tumors in mice; and (iii) decreased the incidence of lung metastases of a malignant tumor implanted intramuscularily in mice. Moreover, besides such cancer risk reduction effects, the dietary treatment with inulin or oligofructose significantly potentiated the effects of subtherapeutic doses of six different cytotoxic drugs commonly utilized in human cancer treatment. If confirmed, such dietary treatment with inulin or oligofructose potentiating cancer therapy might become an interesting approach to complement classical protocols of human cancer treatment without any additional risk for the patients

Nontoxic potentiation of cancer chemotherapy by dietary oligofructose or inulin.

Our previously published results indicated that dietary treatment with oligofructose or inulin inhibited malignant tumor growth in experimental animals. Thus it appeared to be interesting to investigate whether the same treatment could have a positive influence on tumor chemotherapy. The chemotherapy-potentiating effect of 15% oligofructose or inulin incorporated into the basal diet for experimental animals was investigated on a transplantable mouse liver tumor. This dietary adjuvant therapy was started seven days before intraperitoneal transplantation of transplantable liver tumor and was continued until the end of experiments. A single, subtherapeutic dose of six different cytotoxic drugs commonly utilized in treatment of human cancer was intraperitoneally injected 48 hours after tumor transplantation. In all experiments, dietary oligofructose or inulin significantly potentiated the therapeutic effects of six different cytotoxic drugs. Such dietary treatment potentiating cancer chemotherapy could be introduced into classical protocols of human cancer treatment as a new, nontoxic, and easily applicable adjuvant cancer therapy without any supplementary risk for patients