Radiation Protective and Immunopotentiating Effect of Lymphocytes by β-Glucan

Various intractable diseases have been cured by the development of many new medicines. However, cancer is still a major cause of death. We focused on β-glucan which heat treated Enterococcus faecalis in human intestine, and investigated antioxidant activity, antitumor activity, immune response, etc. In this study, we studied the immunostimulatory effect of β-glucan and its application as a radioprotective agent. As a result, β-D-glucan is known to possess antioxidant activity. Its action is thought to be due to radical scavenger reaction. In our study, β-glucan increased the amount of killer cells and suppressor T cells. Therefore, administration of β-glucan is thought to have an anticancer action. In the future, we hypothesize that β-glucan could be used as an immunopotentiating agent which is effective for the prevention of cancer. From now on, further research will be necessary on the search for cancer cell receptors and to conduct fundamental research on the synergistic effects of radiation therapy. β-glucan showed strong antitumor activity against two kinds of solid carcinoma. Taken altogether, this strongly suggests that β-glucan enhances innate functions of macrophages and NK cells, and as a result, secondarily enhances the immune reaction and suppresses tumor growth

New Screening for the Development of Radioprotectors: Radioprotection and Anti-Cancer Effect of β-Glucan (<em>Enterococcus faecalis</em>)

In this study, β-glucan was orally administered and irradiated with whole body 2 Gy. It was then confirmed that the mortality of mice and tumor growth of mice with tumors were significantly reduced. Since the number of leukocytes and lymphocytes increased with a single dose of β-glucan, the crystal was encountered where the radioprotective effect of β-glucan was probably increased by the hematopoietic action of irradiated mice. In previous studies, β-(1–3)-D-glucan extract has a radioprotective effect and an antitumor effect, and regarding the mechanism of action, the immune activity and antioxidant were elucidated. In this study, we investigated the antitumor effects of β-glucan on radiation, protection of immune disorders, and antioxidant effects. After intraperitoneal inoculation of about 2 x 106 sarcoma 180, ICR mice were administered 200 mg/kg β-glucan every other day every two weeks. We irradiated 2 Gy radiation 3 times and counted the number of white blood cells and lymphocytes. In addition, body weight and tumor size were measured 2 weeks after cancer cells were seeded. Antioxidant activity was measured using the AAPH (2,2-azobis (2-amidinopropane) dihydrochloride) method. There was a clear decrease in tumor size in the radiation and glucan groups compared to the group receiving only cancer cells that increased tumor size over time. Almost all mice inoculated with only cancer cells died two weeks after radiation, but two-thirds of radiation and the glucan group were alive. Regardless of radiation exposure, the number of leukocytes and lymphocytes increased when β-glucan was administered. Antioxidant activity has been demonstrated in both groups of glucans. These results may indicate that administration of β-glucan increases immune activity, prevents side effects during cancer radiotherapy, and provides a supplemental tool for the treatment of cancer

Cellular and Molecular Level Mechanisms against Electrochemical Cancer Therapy

Electrochemical treatment (ECT) is a promising new way to induce tumor regression by flowing direct current into the cancer tissue. ECT was applied to different kinds of tumors in clinical studies and showed good results. In addition, basic research has almost not been done in the field of evaluation of efficacy, dose-response, and cytotoxicity. Therefore, the objective is to study the cellular mechanism in the antitumor effect of ECT and to contribute data of basic research of ECT. In the cell-level study, tumor cells (Sarcoma-180, Scc-7, Ehrlich Carcinoma) were studied using ICR mice and C3H mice. In the study group, pH values of control, 10mA × 150secs, 10mA × 300secs, and 10mA × 600secs groups were measured five times each. In histological level studies, ECT was performed on tumors inoculated on the upper part of the right foot of C3H mice. In each group, mice were sacrificed by cervical dislocation 6, 12, and 24 hrs after ECT treatment, and tumors were removed. The excised tumor was fixed in tissue with 10% formalin, and HE staining and apoptosis antibody staining were carried out from the obtained tissue section and observation. In the study at the cellular level, statistically significant differences were observed in all ECT groups in Sarcoma in the tumor growth measurement study compared with the control group. Statistically significant differences were also observed in Scc-7 in all ECT groups compared to the control group. In the intratumoral pH measurement study, there was a statistically significant difference between the anode and the cathode in each group compared to the control group. In the examination at the histological level, microscopic observation of a slide stained with apoptosis antibody with a magnification of 400 times showed that 6hrs after ECT it was stronger and then decreased. By performing ECT, a weak current flows in the living body. As a result, changes in tissue pH, generation of gas, etc. occur. In this study, it was also confirmed that the intratumor pH value becomes strongly acidic on the anode side and strongly alkaline on the cathode side. In addition, this study confirmed the occurrence of gas during treatment of ECT. Changes in the pH and the like cause changes in the environment in the cell, denaturation of proteins, apoptosis, and necrosis. In this study, a significant increase in apoptosis was confirmed in each ECT group compared to the control group. Treatment effects by ECT were also observed in tumor growth measurement studies and tumor weight measurement studies. From these research results, ECT is considered to be effective as a tumor treatment method

Water soluble vitamin E (TMG) as a radioprotector

1365-1371<span style="font-size:14.0pt;mso-bidi-font-size:8.0pt; line-height:115%;font-family:" times="" new="" roman","serif";mso-fareast-font-family:="" "times="" roman";mso-ansi-language:en-us;mso-fareast-language:en-us;="" mso-bidi-language:ar-sa"="">Tocopherol monoglucoside (TMG), a water soluble derivative of vitamin E offers protection against deleterious effects of  ionizing radiation, both under <span style="font-size:14.5pt;mso-bidi-font-size:8.5pt;line-height:115%;font-family: " times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";mso-ansi-language:="" en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">in vivo <span style="font-size:14.0pt;mso-bidi-font-size:8.0pt;line-height:115%;font-family: " times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";mso-ansi-language:="" en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">and <span style="font-size:14.5pt;mso-bidi-font-size:8.5pt;line-height:115%;font-family: " times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";mso-ansi-language:="" en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">in vitro <span style="font-size:14.0pt;mso-bidi-font-size:8.0pt;line-height:115%;font-family: " times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";mso-ansi-language:="" en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">conditions, to biological systems. TMG was found to be a potent antioxidant and an effective free radical scavenger. It forms <span style="font-size:15.5pt; mso-bidi-font-size:9.5pt;line-height:115%;font-family:" times="" new="" roman","serif";="" mso-fareast-font-family:"times="" roman";mso-ansi-language:en-us;mso-fareast-language:="" en-us;mso-bidi-language:ar-sa"="">a <span style="font-size:14.0pt; mso-bidi-font-size:8.0pt;line-height:115%;font-family:" times="" new="" roman","serif";="" mso-fareast-font-family:"times="" roman";mso-ansi-language:en-us;mso-fareast-language:="" en-us;mso-bidi-language:ar-sa"="">phenoxy<span style="font-size:14.5pt; mso-bidi-font-size:8.5pt;line-height:115%;font-family:" arial","sans-serif";="" mso-fareast-font-family:"times="" new="" roman";mso-ansi-language:en-us;mso-fareast-language:="" en-us;mso-bidi-language:ar-sa"="">I <span style="font-size:14.0pt; mso-bidi-font-size:8.0pt;line-height:115%;font-family:" times="" new="" roman","serif";="" mso-fareast-font-family:"times="" roman";mso-ansi-language:en-us;mso-fareast-language:="" en-us;mso-bidi-language:ar-sa"="">radical similar to trolox upon reaction with various one-electron oxidants. TMG protected DNA from radiation-induced strand breaks. It also protected thymine glycol formation induced by gamma-radiation. Gamma-radiation-induced loss of viability of EL-tumor cells and peroxidation of lipids in microsomal and mitochondrial membranes were prevented by TMG. TMG was nontoxic to mice when administered orally up to <span style="font-size: 14.5pt;mso-bidi-font-size:8.5pt;line-height:115%;font-family:" times="" new="" roman","serif";="" mso-fareast-font-family:"times="" roman";mso-ansi-language:en-us;mso-fareast-language:="" en-us;mso-bidi-language:ar-sa"="">7.0 <span style="font-size:14.0pt; mso-bidi-font-size:8.0pt;line-height:115%;font-family:" times="" new="" roman","serif";="" mso-fareast-font-family:"times="" roman";mso-ansi-language:en-us;mso-fareast-language:="" en-us;mso-bidi-language:ar-sa"="">g/kg body weight. The LD50 dose of TMG for ip administration in mice was 1<span style="font-size:14.5pt; mso-bidi-font-size:8.5pt;line-height:115%;font-family:" arial","sans-serif";="" mso-fareast-font-family:"times="" new="" roman";mso-ansi-language:en-us;mso-fareast-language:="" en-us;mso-bidi-language:ar-sa"="">.15 <span style="font-size:14.0pt; mso-bidi-font-size:8.0pt;line-height:115%;font-family:" times="" new="" roman","serif";="" mso-fareast-font-family:"times="" roman";mso-ansi-language:en-us;mso-fareast-language:="" en-us;mso-bidi-language:ar-sa"="">g/kg body wt. In rats, following oral and ip administration of TMG, the absorption (distribution) half lives were <span style="font-size:14.5pt;mso-bidi-font-size:8.5pt;line-height:115%;font-family: " times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";mso-ansi-language:="" en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">5.8 <span style="font-size:14.0pt;mso-bidi-font-size:8.0pt;line-height:115%;font-family: " times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";mso-ansi-language:="" en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">and <span style="font-size:14.5pt;mso-bidi-font-size:8.5pt;line-height:115%;font-family: " times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";mso-ansi-language:="" en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">3.0 <span style="font-size:14.0pt;mso-bidi-font-size:8.0pt;line-height:115%;font-family: " times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";mso-ansi-language:="" en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">min respectively and elimination half  lives were <span style="font-size:14.5pt;mso-bidi-font-size:8.5pt;line-height:115%;font-family: " times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";mso-ansi-language:="" en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">6.7 <span style="font-size:14.0pt;mso-bidi-font-size:8.0pt;line-height:115%;font-family: " times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";mso-ansi-language:="" en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">and <span style="font-size:14.5pt;mso-bidi-font-size:8.5pt;line-height:115%;font-family: " times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";mso-ansi-language:="" en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">3.1 <span style="font-size:14.0pt;mso-bidi-font-size:8.0pt;line-height:115%;font-family: " times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";mso-ansi-language:="" en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">min respectively. Embryonic mortality resulting from exposure of pregnant mice to ionizing radiation <span style="font-size:14.5pt;mso-bidi-font-size:8.5pt;line-height:115%; font-family:" times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";="" mso-ansi-language:en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">(2 <span style="font-size:14.0pt;mso-bidi-font-size:8.0pt;line-height:115%;font-family: " times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";mso-ansi-language:="" en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">Gy) was reduced by <span style="font-size:14.5pt;mso-bidi-font-size:8.5pt;line-height:115%;font-family: " times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";mso-ansi-language:="" en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">75% <span style="font-size:14.0pt;mso-bidi-font-size:8.0pt;line-height:115%;font-family: " times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";mso-ansi-language:="" en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">by ip administration of TMG <span style="font-size:14.5pt;mso-bidi-font-size:8.5pt; line-height:115%;font-family:" times="" new="" roman","serif";mso-fareast-font-family:="" "times="" roman";mso-ansi-language:en-us;mso-fareast-language:en-us;="" mso-bidi-language:ar-sa"="">(0.6 <span style="font-size:14.0pt;mso-bidi-font-size: 8.0pt;line-height:115%;font-family:" times="" new="" roman","serif";mso-fareast-font-family:="" "times="" roman";mso-ansi-language:en-us;mso-fareast-language:en-us;="" mso-bidi-language:ar-sa"="">g/kg, body wt) prior to irradiation. TMG offered protection to mice against whole body gamma-radiation-induced lethality and weight loss. The LD5<span style="font-size:11.0pt; mso-bidi-font-size:5.0pt;line-height:115%;font-family:" arial","sans-serif";="" mso-fareast-font-family:"times="" new="" roman";mso-ansi-language:en-us;mso-fareast-language:="" en-us;mso-bidi-language:ar-sa"="">0(30)<span style="font-size:11.0pt; mso-bidi-font-size:5.0pt;line-height:115%;font-family:" arial","sans-serif";="" mso-fareast-font-family:"times="" new="" roman";mso-ansi-language:en-us;mso-fareast-language:="" en-us;mso-bidi-language:ar-sa"=""> <span style="font-size:14.0pt; mso-bidi-font-size:8.0pt;line-height:115%;font-family:" times="" new="" roman","serif";="" mso-fareast-font-family:"times="" roman";mso-ansi-language:en-us;mso-fareast-language:="" en-us;mso-bidi-language:ar-sa"="">of mice increased from <span style="font-size:14.5pt;mso-bidi-font-size:8.5pt;line-height:115%;font-family: " times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";mso-ansi-language:="" en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">6 <span style="font-size:14.0pt;mso-bidi-font-size:8.0pt;line-height:115%;font-family: " times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";mso-ansi-language:="" en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">to <span style="font-size:14.5pt;mso-bidi-font-size:8.5pt;line-height:115%;font-family: " times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";mso-ansi-language:="" en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">6.72 <span style="font-size:14.0pt;mso-bidi-font-size:8.0pt;line-height:115%;font-family: " times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";mso-ansi-language:="" en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">Gy upon post irradiation administration of a single dose of TMG <span style="font-size:14.5pt; mso-bidi-font-size:8.5pt;line-height:115%;font-family:" times="" new="" roman","serif";="" mso-fareast-font-family:"times="" roman";mso-ansi-language:en-us;mso-fareast-language:="" en-us;mso-bidi-language:ar-sa"="">(0.6 <span style="font-size:14.0pt; mso-bidi-font-size:8.0pt;line-height:115%;font-family:" times="" new="" roman","serif";="" mso-fareast-font-family:"times="" roman";mso-ansi-language:en-us;mso-fareast-language:="" en-us;mso-bidi-language:ar-sa"="">g/kg, body wt) by ip.</span