29 research outputs found
Synergistic potentiation of D-fraction with vitamin C as possible alternative approach for cancer therapy
No full textSensuke KonnoDepartment of Urology, New York, Medical College, Valhalla, NY, USAAbstract: Maitake D-fraction or PDF is the bioactive extract of maitake mushroom (Grifola frondosa) and its active constituent is the protein-bound polysaccharide (proteoglucan), or more specifically known as β-glucan. PDF has been extensively studied and a number of its medicinal potentials/properties have been unveiled and demonstrated. Those include various physiological benefits ranging from immunomodulatory and antitumor activities to treatment for hypertension, diabetes, hypercholesterolemia, viral infections (hepatitis B and human immunodeficiency virus), and obesity. Particularly, two major biological activities of PDF, immunomodulatory and antitumor activities, have been the main target for scientific and clinical research. To demonstrate and confirm such biological activities, numerous studies have been performed in vitro and in vivo or in clinical settings. These studies showed that PDF was indeed capable of modulating immunologic and hematologic parameters, inhibiting or regressing the cancer cell growth, and even improving quality of life of cancer patients. Synergistic potentiation of PDF with vitamin C demonstrated in vitro is rather interesting and may have clinical implication, because such combination therapy appears to help improve the efficacy of currently ongoing cancer therapies. Recently, intravenous administration of vitamin C has been often used to increase its physiological concentration and this useful procedure may further make this combination therapy feasible. Therefore, PDF may have great potential, either being used solely or combined with other agents, for cancer therapy. Such relevant and detailed studies will be described and discussed herein with a special focus on the combination of PDF and vitamin C as a viable therapeutic option.Keywords: maitake D-fraction, PDF, vitamin C, synergism, cancer therap
Synergistic potentiation of D-fraction with vitamin C as possible alternative approach for cancer therapy
No full textSX-fraction: Promise for Novel Treatment of Type 2 Diabetes
No full textSX-fraction (SXF) is a bioactive glycoprotein with anti-diabetic and hypoglycemic activities that have been documented in several reports. We have reviewed those studies herein and also explored the possible mechanism of its hypoglycemic activity. The 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 activity. The 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 activity. To explore the hypoglycemic mechanism of SXF, its possible effects on the insulin signal transduction pathway was examined in vitro. Particularly, 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 cells. The status of these three parameters were examined under a high glucose (35 mmol/L) milieu with SXF and assessed using the enzyme-linked immunosorbent assay. Such 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 pathway. However, such an inactivation was reversed or re-activated by SXF to successfully carry out the sequential signaling events. In fact, a measurement of glucose uptake in cells showed that SXF did increase a glucose uptake while high glucose decreased it. Therefore, 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
Possible disease remission in patient with invasive bladder cancer with D-fraction regimen
No full textPossible hypoglycemic action of SX-fraction targeting insulin signal transduction pathway
No full textSensuke Konno, Bobby Alexander, John Zade, Muhammad ChoudhuryDepartment of Urology, New York Medical College, Valhalla, NY, USABackground: SX-fraction (SXF) is a bioactive glycoprotein with hypoglycemic activity that has been demonstrated in our pilot clinical study. However, how it would actually work in diabetic patients remains unclear. To explore such a mechanism, the effects of SXF on the insulin signal transduction pathway were investigated using skeletal muscle L6 cells in vitro.Methods: L6 cells were first differentiated to myotubes expressing several biochemical parameters that were examined in this study. Myotubes were exposed to a high concentration (35 mM) of glucose (Glc) alone or in combination with SXF or insulin for 24 hours. Possible effects of these agents on activities of insulin receptor (IR), IR substrate 1 (IRS-1), and Akt, which are key elements involved in the signal pathway, were assessed using enzyme-linked immunosorbent assay (ELISA). Any changes in Glc uptake were also determined.Results: High Glc indeed led to inactivation of IR, IRS-1, and subsequent Akt in myotubes, indicating an interruption of the signal pathway. However, such inactivation was reversed or reactivated by SXF, presumably aiding the occurrence of successive signaling events. Measurement of Glc uptake to assess the outcome of this signaling cascade showed that high Glc decreased Glc uptake (interfering with the signal pathway), but SXF was capable of overcoming such a suppressive effect, resulting in the increased Glc uptake. Insulin was used as a positive control in this study and all results were nearly compatible to those obtained from SXF.Conclusion: The present study suggests that SXF may specifically target the insulin signal pathway, and, in particular, the IR and IRS-1 therein that trigger the subsequent signaling events. As a result, SXF could activate such an impaired signal pathway through high Glc or under a hyperglycemic milieu, thereby ultimately facilitating Glc uptake. This may then account for possible hypoglycemic action of SXF.Keywords: diabetes, insulin resistance, mushroom extract, natural remedy, mode of actio
Growth inhibition of androgen-responsive prostate cancer cells with brefeldin A targeting cell cycle and androgen receptor
Get PDFAbstract Background Androgen ablation is one of the viable therapeutic options for patients with primary hormone (androgen)-dependent prostate cancer. However, an antibiotic brefeldin A (BFA) has been shown to exhibit the growth inhibitory effect on human cancer cells. We thus investigated if BFA might inhibit proliferation of androgen-responsive prostate cancer LNCaP cells and also explored how it would be carried out, focusing on cell cycle and androgen receptor (AR). Methods Androgen-mediated cellular events in LNCaP cells were induced using 5α-dihydrotestosterone (DHT) as an androgenic mediator. Effects of BFA on non-DHT-stimulated or DHT-stimulated cell growth were assessed. Its growth inhibitory mechanism(s) was further explored; performing cell cycle analysis on a flow cytometer, assessing AR activity by AR binding assay, and analyzing AR protein expression using Western blot analysis. Results DHT (1 nM) was capable of stimulating LNCaP cell growth by ~40% greater than non-stimulated controls, whereas BFA (30 ng/ml) completely inhibited such DHT-stimulated proliferation. Cell cycle analysis showed that this BFA-induced growth inhibition was associated with a ~75% reduction in the cell number in the S phase and a concomitant increase in the G1 cell number, indicating a G1 cell cycle arrest. This was further confirmed by the modulations of specific cell cycle regulators (CDK2, CDK4, cyclin D1, and p21WAF1), revealed by Western blots. In addition, the growth inhibition induced by BFA was accompanied by a profound (~90%) loss in AR activity, which would be presumably attributed to the significantly reduced cellular AR protein level. Conclusions This study demonstrates that BFA has a potent growth inhibitory activity, capable of completely inhibiting DHT (androgen)-stimulated LNCaP proliferation. Such inhibitory action of BFA appears to target cell cycle and AR: BFA led to a G1 cell cycle arrest and the down-regulation of AR activity/expression, possibly accounting for its primary growth inhibitory mechanism. Thus, it is conceivable that BFA may provide a more effective therapeutic modality for patients with hormone-dependent prostate cancer.</p
Possible immunotherapeutic potentiation with D-Fraction in prostate cancer cells
Get PDFAbstract Background Prostate cancer remains the most common malignancy among elderly men and the second leading cause of cancer death in the United States. Although several conventional therapies are currently available, they have a low efficacy and the more effective treatment modalities need to be established. Interferons (IFNs) are one of such options known as immunotherapy and demonstrated their antitumor effects on certain cancer types. Yet such antitumor activity should be improved or potentiated to have the satisfactory outcomes. In fact, combination therapy has been proposed as an alternative approach and is being underway in human and animal studies. Accordingly, we studied whether the combination of IFN-α and D-fraction (PDF), a bioactive mushroom extract, might potentiate anticancer activity of IFN-α in prostate cancer PC-3 cells in vitro. Results Potential effects of recombinant IFN-α2b (0–100,000 IU/ml), PDF (0���1,000 μg/ml), or their combinations were assessed on the growth of PC-3 cells at 72 h. Cell cycle analysis using a flow cytometer and Western blot analysis were performed to explore antiproliferative mechanism of these agents. The dose-dependent study showed that IFN-α2b up to 20,000 (20 K) IU/ml had no significant effects, but >60% growth reduction was attained ≤50 K IU/ml. Similarly, PDF showed no effects up to 250 μg/ml but ~65% growth reduction was seen at 1,000 μg/ml. When IFN-α2b and PDF were combined, a relatively low concentration (10 K IU/ml) of IFN-α2b and PDF (250 μg/ml) resulted in a ~65% growth reduction. This was accompanied by a G1 cell cycle arrest, indicated by cell cycle analysis. Western blots also revealed that the G1-specific cell cycle regulators, CDK2, CDK4, CDK6, cyclin D1, and cyclin E, had been significantly (>60%) down-regulated in IFN/PDF-treated cells. Conclusion The combination of IFN-α2b (10 K IU/ml) and PDF (250 μg/ml) is capable of inducing a ~65% reduction in PC-3 cell growth. This appears to be due to a synergistic potentiation of two agents, leading to a G1 cell cycle arrest. Thus, it is conceivable that PDF may potentiate IFN-α2b activity, improving immunotherapy for prostate cancer.</p
Alternative Therapeutic Approach to Renal-Cell Carcinoma: Induction of Apoptosis With Combination of Vitamin K3 and D-Fraction
No full textPURPOSE: Because of a dismal prognosis for advanced renal-cell carcinoma (RCC), an alternative therapeutic approach, using vitamin K3 (VK3) and D-fraction (DF) was investigated. VK3 is a synthetic VK derivative and DF is a bioactive mushroom extract, and they have been shown to have antitumor activity. We examined if the combination of VK3 and DF would exhibit the improved anticancer effect on RCC in vitro.
MATERIALS AND METHODS: Human RCC, ACHN cell line, were treated with varying concentrations of VK3, DF, or a combination of the two. Cell viability was assessed at 72 hours by MTT assay. To explore the possible anticancer mechanism, studies on cell cycle, chromatin modifications, and apoptosis were conducted.
RESULTS: VK3 alone led to a ~20% reduction in cell viability at 4 μM, while DF alone induced a 20% to 45% viability reduction at ≥ 500 μg/mL. A combination of VK3 (4 μM) and DF (300 μg/mL) led to a drastic \u3e90% viability reduction, however. Cell cycle analysis indicated that VK3/DF treatment induced a G1 cell cycle arrest, accompanied by the up-regulation of p21(WAF1) and p27(Kip1). Histone deacetylase (HDAC) was also significantly (~60%) inactivated, indicating chromatin modifications. In addition, Western blot analysis revealed that the up-regulation of Bax and activation of poly-(ADP-ribose)-polymerase (PARP) were seen in VK3/DF-treated cells, indicating induction of apoptosis.
CONCLUSIONS: The combination of VK3 and DF can lead to a profound reduction in ACHN cell viability, through a p21(WAF1)-mediated G1 cell cycle arrest, and ultimately induces apoptosis. Therefore, the combination of VK3/DF may have clinical implications as an alternative, improved therapeutic modality for advanced RCC
