Persimmon Leaf Flavonols Enhance the Anti-Cancer Effect of Heavy Ion Radiotherapy on Murine Xenograft Tumors

The cell cycle checkpoint system play a pivotal role in the cellular DNA damage response, and the discovery of checkpoint inhibitors is expected to sensitize current cancer therapies. Checkpoint signaling cascades are critically modulated by ATM (ataxia telangiectasia-mutated) and its related molecules. Generally, ATM primarily responds to ionizing irradiation-induced DNA double-strand breaks. Heavy ions from an accelerated carbon ion beam have been used to cure cancer because they are more effective than ionizing irradiation such as X-ray and γ-radiation in terms of biological damage. In a previous study, we demonstrated that a persimmon leaf flavonol (PLF) promoted the cytotoxic effect of chemotherapeutic agents on cancer cells through inhibition of checkpoint activities, especially in the ATM dependent pathway. The present study investigated whether PLF inhibits checkpoint activity during the DNA damage response induced by heavy ion irradiation. Treatment with PLF significantly increased the cytotoxicity of heavy ion irradiation in A549 adenocarcinoma cells. The phosphorylation of checkpoint proteins such as p53, SMC1, and Chk1 was increased by heavy ions. PLF reduced the phosphorylation of checkpoint proteins. Pre-treatment with PLF significantly prevented the decrease of mitotic cells in heavy ion-exposed cells. We further evaluated tumor volume in SCID mice inoculated with human lung adenocarcinoma A549 cells. The combination treatment of PLF and heavy ion resulted in a decrease of tumor volume compared with controls, although PLF itself did not exhibit any effect. These results indicate that PLF inhibits tumor growth through modulation of the DNA damage response. PLF may be useful for clinical application in combination with heavy ion radiotherapy.

Cerebral Oxidative Stress as Mibyo Pathology:Target for Disease Prevention.

The Mibyo(sub-healthy condition)was defined in ancient oriental medicine as the physiological condition that is not comple.tely healthy but not ill.This ideas is also quite important in current preventive medicine.In the traditional oriental medicine,the same prescription of Kampo and Chinese

Characteristics of <i>Morus alba</i>L. Cultured by In-Room Hydroponics

Morus alba L., (cv Ichinose) was cultivated by in-room hydroponics. The flavor and texture of leaves were markedly improved enough to be edible. When the contents of 1-deoxynojirimycin (DNJ) and polyphenols were measured in the hydroponic cultivar, DNJ increased in the leaf compared to the field grown M. alba. However, polyphenols, in contrast, decreased compared to the field cultivar. HPLC profiling revealed marked difference in leaf components between hydroponic and field cultivars indicating relative contents of lipophilic polyphenols were increased. The polyphenols contents, especially, lipophilic polyphenols in the root were remarkably high compared to So-Haku-Hi (Sang Bai Pi in Chinese). The anti-obesity effect of the hydroponically grown Morus was further studied in rats by feeding high-fat, high-sucrose (HFHS) diet with and without supplementation of dried leaf and root powders for 15 weeks. As the result, both the leaf and root from the hydroponic cultivar showed potential anti-obesity and anti-hyperlipidemic functions through amelioration of insulin resistance. Differential effects of leaf and root powders indicated that besides DNJ, the lipophilic polyphenols may play a crucial role in the anti-diabetic function of hydroponically grown Morus alba L. The hydroponics will provide an alternate way to cultivate a novel resource of Morus for developing functional foods and medicines.