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SX-fraction:Promise for novel treatment of type 2 diabetes

World Journal of Diabetes 2020年第12期11卷 572-583页

作者： sensuke konno Department of Urology New York Medical CollegeValhallaNY 10595United States

SX-fraction(SXF)is a bioactive glycoprotein with anti-diabetic and hypoglycemic activities that have been documented in several *** have reviewed those studies herein and also explored the possible mechanism of its hypoglycemic *** early animal studies of SXF using diabetic mice showed the significant reduction in the three diabetic parameters,serum glucose,insulin,and triglyceride,suggesting its anti-diabetic *** limited clinical studies also showed that SXF led to the significant reduction in the fasting blood glucose levels of type 2 diabetic patients within 2 wk or a month,suggesting its hypoglycemic *** explore the hypoglycemic mechanism of SXF,its possible effects on the insulin signal transduction pathway was examined in ***,activities of insulin receptor,insulin receptor substrate 1,and protein kinase B,which are essential elements playing a key regulatory role in the signal pathway,were studied using skeletal muscle L6 *** status of these three parameters were examined under a high glucose(35 mmol/L)milieu with SXF and assessed using the enzyme-linked immunosorbent *** studies revealed that all three parameters(insulin receptor,insulin receptor substrate 1,and protein kinase B)were inactivated by high glucose,indicating a disruption of the signal ***,such an inactivation was reversed or re-activated by SXF to successfully carry out the sequential signaling *** fact,a measurement of glucose uptake in cells showed that SXF did increase a glucose uptake while high glucose decreased ***,SXF has anti-diabetic and hypoglycemic activities through activation of the insulin signal pathway and appears to be a safe,natural agent for lowering the serum glucose levels in type 2 diabetic patents and improving their diabetic conditions.

关键词： SX-fraction Diabetes Anti-diabetic Hypoglycemic Insulin signal pathway

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Potent Anticancer Effect of PET-Fraction (PET-F) in Comparison with Other Commercial Products on Canine Cancer Cells

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Open Journal of Veterinary Medicine 2015年第5期5卷 101-110页

作者： sensuke konno Muhammad Choudhury Department of Urology New York Medical College Valhalla USA

A variety of nutritional supplements are commercially available for the potential therapeutic purpose for dogs and other domestic animals with cancers. However, the efficacy of these supplements on those cancer-bearing animals has not been verified and remains uncertain, due to the lack of the sufficient scientific studies/data. To address this important issue, we examined actual anticancer effects of five selected commercial products on the two types of canine cancer models in vitro. Among them, PET-Fraction (PET-F) obtained from maitake mushroom has been shown to have potent anticancer effect on canine cancer cells. In comparison with this PET-F, possible anticancer effects of the rest of four products were examined. Two of four products were found to have the significant anticancer effects on both cancer cells, while other two products had little effects. Nevertheless, PET-F exhibited the best anticancer effect. Cell cycle analysis indicated that the PET- F-induced growth reduction was attributed to a G1 cell cycle arrest, and Western blot analysis further revealed that such a growth reduction was coupled with apoptosis. Moreover, anticancer activity of PET-F was remarkably enhanced with vitamin C, but no such synergistic effect was seen with other four products. Therefore, although two other products besides PET-F yet have anticancer activities, PET-F appears to be the most potent and promising commercial product that can be useful in effectively and safely treating canine cancers.

关键词： Canine Cancer Cells Commercial Supplements PET-Fraction Vitamin C Anticancer

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Potential Anticancer Effect of Bioactive Extract of Monk Fruit (Siraitia grosvenori) on Human Prostate and Bladder Cancer Cells

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Journal of Cancer Therapy 2023年第5期14卷 211-224页

作者： Rogerio Haung Akhil Saji Muhammad Choudhury sensuke konno Department of Urology New York Medical College Valhalla USA

Prostate and bladder cancers are the two prevalent urological cancers, and several therapeutic options are currently available but the outcomes have not been satisfactory. To find the better therapeutic option, we investigated if the bioactive extracts of monk fruit, mogrosides, with potential anticancer activity might have anticancer effect against prostate and bladder cancer cells. Four of commercial products made of mogrosides known as Lakantoò (LKT) products, LK1, LK2, LLE, and MOG, were then tested. A dose-dependent study at given concentrations of four products showed that LK1 and LK2 had little effects, while LLE and MOG showed a significant cell viability reduction in both PC-3 and T24 cells. To explore the anticancer mechanism of such products, cell cycle analysis was first performed. Such analysis revealed that LLE and MOG, not LK1 and LK2, led to a G1 cell cycle arrest. Potential induction of endoplasmic reticulum (ER) stress was next examined because it is known to be linked to a cell cycle arrest. The three key regulators involved in ER stress were all up-regulated with LLE or MOG, indicating induction of ER stress. As ER stress is also known to induce apoptosis, this possibility was tested. The two apoptotic regulators were modulated in a specific manner with LLE or MOG, indicating induction of apoptosis. Lastly, to validate anticancer effect of LLE or MOG, anticancer effect of four chemotherapeutic drugs was also assessed in comparison with that of LLE/MOG. None of drugs had any effects but two products showed significant anticancer effect. In conclusion, two monk fruit products, LLE and MOG, demonstrated anticancer activity against PC-3 and T24 cells, significantly reducing cell viability and ultimately inducing apoptosis. Therefore, these two LKT products with few side effects may have clinical implications in the treatment of urological cancers.

关键词： Monk Fruit Mogroside Anticancer Prostate Cancer Bladder Cancer Lakanto

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Improved Anticancer Effects on Various Cancers with Combinations of Chemotherapeutic Drugs or Vitamin C and D-Fraction

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Journal of Cancer Therapy 2013年第4期4卷 843-850页

作者： sensuke konno Bobby Alexander Drew Freilich Muhammad Choudhury Department of Urology New York Medical College Valhalla USA

Although chemotherapy is one of several therapeutic options for cancer patients, the outcomes have been less satisfactory with palpable side effects in many cases. To help improve the efficacy of chemotherapy, we examined whether D-fraction (DF), a bioactive mushroom extract, would potentiate anticancer effects of those drugs in vitro. Seven types of cancer cell lines, including breast, lung, stomach, colon, prostate, bladder, and kidney cancers, were tested with various chemotherapeutic drugs and their combinations with DF. Compared to individual drugs alone, combinations of those drugs and DF have indeed improved anticancer activity, resulting in the significant (p 0.05) cell viability reduction in all cancer cells. As vitamin C (VC) has been insinuated to potentiate bioactivity of DF, combination of DF (300 μg/ml) and VC (200 μM) was also examined. Such studies showed that DF/VC combination led to the drastic (≥90%) viability reductions in 6 cancer cells and the 70% reduction in 1 cancer cell type. These results were superior to those from combinations of drugs and DF. To assess if such a profound cell viability reduction by DF/VC combination might be attributed to apoptosis, this possibility was tested by Western blots. Analyses revealed that anti-apoptotic bcl-2 was down-regulated while pro-apoptotic Bax was up-regulated with DF/VC combination, indicating induction of apoptosis. It is plausible that DF/VC combination may induce apoptosis, resulting in the severe cell viability reduction. Therefore, DF may have a great potential as an adjuvant agent that can be combined with chemotherapeutic drugs or with VC for the improved treatment of various human malignancies.

关键词： D-Fraction Vitamin C Chemotherapy Apoptosis Human Cancers Maitake

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Chemosensitizing Effect of Monk Fruit Extract on Human Bladder Cancer Cells

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Journal of Cancer Therapy 2024年第6期15卷 250-264页

作者： sensuke konno Jonathan Wong Andrew Penunuri Kelvin Zheng Muhammad Choudhury Department of Urology New York Medical College Valhalla New York USA

The outcomes of chemotherapy have been unsatisfactory with the palpable side effects. We hypothesized that natural products might help improve chemotherapy with few side effects. Recently, we came across the bioactive extracts of monk fruit (Siraitia grosvenori) with anticancer activity. We then investigated if these extracts might have chemosensitizing effect to improve the efficacy of drugs clinically used today. Four different drugs, cisplatin (CPL), carboplatin (CBL), mitomycin C (MMC), and gemcitabine (GEM), were used in this study. Human bladder cancer T24 cells were treated with each drug itself or drug combined with either LLE or MOG (two types of monk fruit extracts). Cell viability was determined to assess anticancer effect and also explored the anticancer mechanism of such combinations, focusing on the status of glycolysis, cell cycle, and chromatin structure. Cell viability test showed that all drugs had anticancer activity, reducing cell viability, but only CPL showed the enhanced anticancer effect when combined with LLE (not with MOG). The rest of three drugs had no such effects with LLE or MOG. The CPL/LLE combination was found to disrupt glycolysis, by inhibiting hexokinase activity, resulted in the decreased ATP synthesis. This combination also blocked the cell cycle progression, due to a G1 cell cycle arrest. Moreover, the two epigenetic regulators, DNA methyltransferase and histone deacetylase, were inactivated with the combination, indicating chromatin modifications. Ultimately, these treated cells were found to undergo apoptosis. In conclusion, anticancer activity of CPL can be significantly enhanced with LLE. This chemosensitizing effect is attributed to the glycolysis inhibition, a G1 cell cycle arrest, and chromatin modifications, ultimately leading to apoptosis. Thus, certain natural products such as LLE could be used as an adjuvant agent in current chemotherapy, improving the drug efficacy but minimizing side effects.

关键词： Monk Fruit Anticancer Bladder Cancer Chemosensitization Lakanto

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舞茸的神奇功效

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作者： (美)Harry G Preuss (美)sensuke konno[]

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Possible Chemosensitizing and Potent Anticancer Effects of D-Fraction in Combination with Vitamin C on Three Prevalent Urologic Cancer Cells

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Journal of Cancer Therapy 2014年第14期5卷 1402-1411页

作者： Drew Freilich Eric Moskowitz Nicholas Feuer Muhammad Choudhury John Phillips sensuke konno Department of Urology New York Medical College Valhalla USA

Chemotherapy is currently one of the most common therapeutic options for cancer patients despite the poor efficacy with considerable side effects. We then examined if D-fraction (DF), a bioactive mushroom extract, could potentiate (poor) anticancer effects of those drugs?in vitro. Three urologic cancers, prostate, bladder, and kidney cancers, were tested with various chemotherapeutic drugs and their combinations with DF. Compared to individual drugs alone, combinations of drugs and DF have improved anticancer activity, resulting in the significant (P < 0.05) cell viability reduction in all three cancer cells. As vitamin C (VC) has been postulated to potentiate the bioactivity of DF, this possibility was also examined. The specific combination of DF (300 μg/ml) and VC (200 μM) indeed led to the drastic (≥90%) viability reductions in all three cancer cells. To have a better understanding of such a profound viability reduction, the effect of DF/VC combination on cell cycle was examined next. Cell cycle analysis indicated that this combination induced a G1cell cycle arrest, which was also confirmed by the down-regulation of specific cell cycle regulators (CDK2, CDK4, and cyclin D1) detected on western blots. Moreover, it was crucial to address if the DF/VC-induced viability reduction could be also linked to apoptosis. Western blot analysis revealed that anti-apoptotic bcl-2 was down-regulated while pro-apoptotic Bax was up-regulated with DF/VC combination in all cancer cells, indicating induction of apoptosis. Therefore, the DF/VC combination could ultimately induce apoptosis, accounting for the severe cell viability reduction. In conclusion, DF appears to be a promising agent with chemosensitizing effect, enhancing the efficacy of chemotherapeutic drugs, and its combination with VC exhibits a potent anticancer effect, which is far superior to any combinations of drugs and DF tested in three prevalent urologic cancer cells.

关键词： Mushroom Extract Chemosensitizing Effect Anticancer Effect Combination Therapy Urologic Cancers

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Base Metal-Catalyzed Transformation of Tetrafluoro ethylene

Base Metal-Catalyzed Transformation of Tetrafluoro ethylene

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中国化学会第十五届全国氟化学会议

作者： sensuke Ogoshi Department of Applied Chemistry Osaka University

Tetrafluoroethylene(TFE) is a major feedstock in the fluorine industry and its Global Warming Potential(GWP), an evaluation system of greenhouse gas effect, is considered to be negligible(GWP: TFE ≈ 0, CO =1, CH = 25, CF = 6500). It means TFE is one of the most ideal starting materials for the synthesis of fluorinated organic compounds. However most of TFE has been consumed as a monomer of fluorinated polymers including polytetrafluoroethylene(PTFE) known as Teflon. Therefore, new methods that allow us to convert TFE into more variable fluorinated organic compounds have been awaited. In 2008, when we started this project, there was no catalytic carbon-carbon bond forming reaction of perfluoro alkenes including TFE via C-F bond activation has been reported. In 2011, we have reported palladiumcatalyzed coupling reactions of TFE with arylzinctaes to give α,β,β-trifluorostyrenes, which was the first catalytic C-C bond forming reaction of perfluoro alkenes. In addition, the coupling reactions with either arylboronates or arylsilanes have been reported as well. Recently, nickel-catalyzed reactions of co-trimerization of TFE with ethylene or TFE and ethylene with aldehyde to give the corresponding alkenes or ketones have been developed(eq. 2). In addition, the synthesis of an expected material to be used in the next generation of active-matrix liquid crystal displays has been achieved by using copper-mediated diarylation of TFE(Fig. 1)(eq 3).

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