• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5339-5343
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• 2012

The induction of apoptosis in target cells is a key mechanism for most anti-tumor therapies. Bufalin is a cardiotonic steroid that has the potential to induce differentiation and apoptosis of tumor cells. Research on bufalin has so far mainly involved leukemia, prostate cancer, gastric cancer and liver cancer, and has been confined to in vitro studies. The bufadienolides bufalin and cinobufagin have been shown to induce apoptosis in a wide spectrum of cancer cell. The present article reviews the anticancer effects of bufalin. It induces apoptosis of lung cancer cells via the PI3K/Akt pathway and also suppressed the proliferation of human non-small cell lung cancer A549 cell line in a time and dose dependent manner. Bufalin, bufotalin and gamabufotalin, key bufadienolides, significantly sensitize human breast cancer cells with differing ER-alpha status to apoptosis induction by the TNF-related apoptosis-inducing ligand (TRAIL). In addition, bufadienolides induce prostate cancer cell apoptosis more significantly than that in breast epithelial cell lines. Similar effects have been observed with hepatocellular carcinoma (HCC) but the detailed molecular mechanisms of inducing apoptosis in this case are still unclear. Bufalin exerts profound effects on leukemia therapy in vitro. Results of multiple studies indicate that bufalin has marked anti-tumor activities through its ability to induce apoptosis. Large-scale randomized, double-blind, placebo or positive drug parallel controlled studies are now required to confirm the efficacy and apoptosis-inducing potential of bufalin in various cancers in the cliniucal setting.

• The Korea Journal of Herbology
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• v.38 no.4
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• pp.31-43
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• 2023

Objectives : The objective of this study was to investigate the phytochemistry and pharmacological activities of Cirsium setidens. Methods : Domestic and international articles about Cirsium setidens were investigated. A review was perfoemed via DB searching engine such as Sci.Direct, Springer, DBpia, KISS, Google scholar, Kipris, and so on. Total 73 listed literature were classified by compound analysis and pharmacological efficacy. Results : C. setidens contains pectolinarin and its glycoside, pectolinarigenin as index compounds, and linarin, apigenin, diosmetin, scopoletin, acacetin, cirsimarin, cirsimaritin, setidenosides A and B, silymarin, hispidulin, 92 volatile compounds, and 15 fatty acids. The Pharmacological activities of C. setidens has been reported to inhibit of platelet aggregation and fat accumulation in the liver, inhibit to hepatitis, anti-cancer, antibacterial, skin improvement, hair growth, liver protection, anti-diabetic, anti-inflammatory, sedative. Also, It has been reported the effect of cholesterol-lowering and anti-obesity, neuroprotective effects, increasing human stem cell viability, inhibiting osteoclast formation and osteogenic differentiation. Conclusion : This reviews showed that C. setidens which has been traditionally used for the treatment of inflammation and hypertension, has anticancer and river protective effect, as well as hair loss and diet. In order to maximize the efficacy of C. setidens, research has also begun on the effect of processing processes such as fermentation or fine powdering and combining natural plant resources.

• Nutritional Sciences
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• v.7 no.3
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• pp.133-137
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• 2004

The present study was designed to investigate the effects of genistein, daidzein, and quercetin on the antioxidative systems of normal rats. Male Sprague-Dawley rats were divided randomly into seven groups and treated with flavonoids at either 2 or 20 mg/day or through vehicle for four weeks. Lipid peroxidation in the liver was inhibited significantly following administration of quercetin. Genistein and daidzein did not have significant effects except in rats treated with 20mg daidzein/day. Genistein and daidzein treatment did not affect the content of $\alpha$-tocopherol in the serum and liver, while quercetin caused a slight increase. In hepatic glutathione and its related enzymes, genistein and daidzein treatment tended to cause a decrease in $\alpha$-tocopherol content, although no significant difference was found. However, quercetin treatment significantly decreased the content of glutathione together with the activity of glutathione reductase in all doses in the liver but there was no significant difference in the brain. Interestingly, daidzein treatment in the brain at 2mg/day significantly increased glutathione (27.1% p＜0.05) compared with the control group, while at 20mg/day glutathione decreased significantly (26.6%, p＜0.05). In conclusion, genistein has not antioxidant effects. Daidzein quercetin may have the capacity to produce not only antioxidants but also have adverse effects including the production of pro-oxidants. Therefore, people should consider consumption at a high dosage.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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• pp.2681-2684
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• 2014

Aim: To compare drainage alone or combined with anti-tumor therapy for treatment of obstructive jaundice caused by recurrence and metastasis after primary tumor resection. Materials and Methods: We collect 42 patients with obstructive jaundice caused by recurrence and metastasis after tumor resection from January 2008 - August 2012, for which percutaneous transhepatic catheter drainage (pTCD)/percutaneous transhepatic biliary stenting (pTBS) were performed. In 25 patients drainage was combined with anti-tumor treatment, antineoplastic therapy including intra/postprodure local treatment and postoperative systemic chemotherapy, the other 17 undergoing drainage only. We assessed the two kinds of treatment with regard to patient prognosis. Results: Both treatments demonstrated good effects in reducing bilirubin levels in the short term and promoting liver function. The time to reobstruction was 125 days in the combined group and 89 days in the drainage only group; the mean survival times were 185 and 128 days, the differences being significant. Conclusions: Interventional drainage in the treatment of the obstructive jaundice caused by recurrence and metastasis after tumor resection can decrease bilirubin level quickly in a short term and promote the liver function recovery. Combined treatment prolongs the survival time and period before reobstruction as compared to drainage only.

• BMB Reports
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• v.49 no.2
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• pp.105-110
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• 2016

Ursodeoxycholic acid (UDCA), a natural, hydrophilic nontoxic bile acid, is clinically effective for treating cholestatic and chronic liver diseases. We investigated the chronic effects of UDCA on age-related lipid homeostasis and underlying molecular mechanisms. Twenty-week-old C57BL/6 male and female mice were fed a diet with or without 0.3% UDCA supplementation for 25 weeks. UDCA significantly reduced weight gain, adiposity, hepatic triglyceride, and hepatic cholesterol without incidental hepatic injury. UDCA-mediated hepatic triglyceride reduction was associated with downregulated hepatic expression of peroxisome proliferator-activated receptor-γ, and of other genes involved in lipogenesis (Chrebp, Acaca, Fasn, Scd1, and Me1) and fatty acid uptake (Ldlr, Cd36). The inflammatory cytokines Tnfa, Ccl2, and Il6 were significantly decreased in liver and/or white adipose tissues of UDCA-fed mice. These data suggest that UDCA exerts beneficial effects on age-related metabolic disorders by lowering the hepatic lipid accumulation, while concurrently reducing hepatocyte and adipocyte susceptibility to inflammatory stimuli.

• Journal of Ginseng Research
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• v.47 no.4
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• pp.534-542
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• 2023

Background: Ginsenoside Rg1, a bioactive component of Ginseng, has demonstrated anti-inflammatory, anti-cancer, and hepatoprotective effects. It is known that the epithelial-mesenchymal transition (EMT) plays a key role in the activation of hepatic stellate cells (HSCs). Recently, Rg1 has been shown to reverse liver fibrosis by suppressing EMT, although the mechanism of Rg1-mediated anti-fibrosis effects is still largely unclear. Interestingly, Smad7, a negative regulator of the transforming growth factor β (TGF-β) pathway, is often methylated during liver fibrosis. Whether Smad7 methylation plays a vital role in the effects of Rg1 on liver fibrosis remains unclear. Methods: Anti-fibrosis effects were examined after Rg1 processing in vivo and in vitro. Smad7 expression, Smad7 methylation, and microRNA-152 (miR-152) levels were also analyzed. Results: Rg1 significantly reduced the liver fibrosis caused by carbon tetrachloride, and reduced collagen deposition was also observed. Rg1 also contributed to the suppression of collagenation and HSC reproduction in vitro. Rg1 caused EMT inactivation, reducing Desmin and increasing E-cadherin levels. Notably, the effect of Rg1 on HSC activation was mediated by the TGF-β pathway. Rg1 induced Smad7 expression and demethylation. The over-expression of DNA methyltransferase 1 (DNMT1) blocked the Rg1-mediated inhibition of Smad7 methylation, and miR-152 targeted DNMT1. Further experiments suggested that Rg1 repressed Smad7 methylation via miR-152-mediated DNMT1 inhibition. MiR-152 inhibition reversed the Rg1-induced promotion of Smad7 expression and demethylation. In addition, miR-152 silencing led to the inhibition of the Rg1-induced EMT inactivation. Conclusion: Rg1 inhibits HSC activation by epigenetically modulating Smad7 expression and at least by partly inhibiting EMT.

• Journal of the East Asian Society of Dietary Life
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• v.21 no.6
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• pp.871-876
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• 2011

In the present study, we investigated the compositions, antioxidant activities and anti-tumor effects of Artemisia princeps Pampanini (APD) as well as blanched leaves (CNBD) and dried leaves (CND) from Cirsium setidens Nakai on HepG2 cells. Water and ash contents were increased in CND. Protein and lipid contents were increased in CNBD. K, Ca, Mg, Fe and Cu contents of CND were higher than those of CNDB and APD. P contents was significantly decreased in CND. Yields of CND was reached high levels, but TPC, TFC, acacetin, apigenin, cynarin contents, and antioxidant activity were higher in APD. Viability of HepG2 liver cells was significantly decreased in APD. Therefore, extracts of APD are more effective preventing the liver cancer than extracts of CND and CNBD.

• The Journal of Korean Medicine
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• v.37 no.2
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• pp.76-84
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• 2016

Objectives: We evaluated the anti-fatigue effects of Rh2-enriched Korean ginseng (Ginseng Rh2+) using a forced exercise-induced chronic fatigue mouse model. Methods: ICR male mice were subjected to running wheel for 1 h, 5 days/week during 4 weeks, and running velocity was gradually increased. Each running session was followed by oral administration of distilled water, Ginseng Rh2+ (150 or 300 mg/kg), or N-acetyl-L-cysteine (NAC, 100 mg/kg) 1 h later. The exercise tolerance and forced swimming test were performed to evaluate the fatigue condition. Results: Chronic forced exercise reduced the physical activity, as evidenced by the behavioral tests, which were notably ameliorated by Ginseng Rh2+ treatment. Ginseng Rh2+ treatment also attenuated the alterations of energy metabolism and oxidative stress in skeletal muscle tissues and/or sera, including malondialdehyde (MDA), lactate concentration and its related factors (lactate dehydrogenase, blood urea nitrogen, and glucose levels). Conclusion: These findings strongly suggest that Ginseng Rh2+ exerts a potent anti-fatigue effect through modulation of energy metabolism and oxidative response.

• Journal of Acupuncture Research
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• v.17 no.1
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• pp.251-286
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• 2000

To study the effects of anti-cancer, anti-metastasis and immune response improvement of aqua-acupuncture with Cistanches Herba infusion solution, we used Cistanches Herba infusion solution(taken by water-alcohol method) put into Chung-wan(CV12) and Chok-Samni(S36) of BALB/c or C57BL/6 which are corresponding to human body. We observed the cytotoxicity, the effect on the expression of MMP-9 gene, the ability to control cancer cell proliferation, change of body weight, surviving number, MST, ILS, changes in amount of WBC, RBC, PLT, total protein, creatinine, glucose and LDH, weight of spleen, number of pulmonary colony, histological analysis on tissue metastasis of lung and liver, splenic cell proliferation, the expression of cytokine gene, the number of $CD4^+$, $CD8^+$, $CD19^+$ and NK cell, and concluded like this. The results were obtained as follows : 1. The cytotoxicity about B16-F10 cell line of $2^0$, $2^{-1}$, $2^{-2}$, $2^{-5}$ diluent groups in Cistanches Herba infusion solution treatment was inhibited significantly, compared with control group. 2. The cytotoxicity about HT1080 cell line of $2^0$, $2^{-1}$, $2^{-2}$, $2^{-3}$, $2^{-5}$, $2^{-8}$ diluent groups in Cistanches Herba infusion solution treatment was inhibited significantly, compared with control group. 3. The effect on expression of MMP-9 gene was decreased in all the sample groups, compared with control group. 4. The effect on the control-ability on the cancer cell proliferation showed cytotooicity significantly in $2^0$, $2^{-1}$, $2^{-2}$, $2^{-3}$, $2^{-4}$, $2^{-5}$ diluent groups. 5. S-180 cancer cell line transplants in BALB/c mice were inhibited significantly in weight increase in all the sample groups, compared with control group. The surviving number increased in almost sample groups, except one group put into Chok-Samni(S36) with 20% Cistanches Herba infusion solution treatment group that showed same number of the control group. 6. S-180 cancer cell line transplants in BALB/c mice showed high MST and ILS significantly in almost sample groups, compared with control group. But one group put into Chok-Samni(S36) with 20% Cistanches Herba infusion solution treatment group showed low MST and ILS than control group. 7. The sample group injected in vein with B16-F10 cancer cell line in C57BL/6 mice showed increased ILS compared with control group significantly in anti-metastasis test. 8. The sample group injected in vein with B16-F10 cancer cell line in C57BL/6 mice were increased significantly in the number of WBC and glucose, and decreased significantly in the amount of LDH, compared with control group. However, there's no significant increase or decrease in number of RBC, PLT, total protein and creatinine. 9. We couldn't find any significant relation in spleen weight of the sample group. 10. In pulmonary colony, sample group was decreased significantly, compared with control group. 11. Histological analysis of sample group inhivited compared with that of control group in both of lung and liver. 12. In immune system, all the sample groups showed having more relevancy to the effect on splenic cell proliferation than normal group. 13. The effect on cytokine gene expression of all the sample groups were increased than control group. 14. In flow cytometry there's no significant relation in number of $CD8^+$, $CD19^+$ cell, however, the number of $CD4^+$ cell and NK cell in sample groups were increased than in control group. Above the results showed that aqua-acupuncture of Cistanches Herba infusion solution has effects of anti-cancer, anti-metastasis and immune response improvement.

• Nutrition Research and Practice
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• v.2 no.2
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• pp.80-84
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• 2008

Beneficial effects of dehydroepiandrosterone (DHEA) supplement on age-associated chronic diseases such as cancer, cardiovascular disease, insulin resistance and diabetes, have been reported. However, its mechanism of action in hepatocellular carcinoma in vivo has not been investigated in detail. We have previously shown that during hepatocellular carcinogenesis, DHEA treatment decreases formation of preneoplastic glutathione S-transferase placental form-positive foci in the liver and has antioxidant effects. Here we aimed to determine the mechanism of actions of DHEA, in comparison to vitamin E, in a chemically-induced hepatocellular carcinoma model in rats. Sprague-Dawley rats were administered with control diet without a carcinogen, diets with 1.5% vitamin E, 0.5% DHEA and both of the compounds with a carcinogen for 6 weeks. The doses were previously reported to have anti-cancer effects in animals without known toxicities. With DHEA treatment, cytosolic malate dehydrogenase activities were significantly increased by ${\sim}5$ fold and glucose 6-phosphate dehydrogenase activities were decreased by ${\sim}25%$ compared to carcinogen treated group. Activities of Se-glutathione peroxidase in the cytotol was decreased siguificantly with DHEA treatment, confirming its antioxidative effect. However, liver microsomal cytochrome P-450 content and NADPH-dependent cytochrome P-450 reductase activities were not altered with DHEA treatment. Vitamin E treatment decreased cytosolic Se-glutathione peroxidase activities in accordance with our previous reports. However, vitamin E did not alter glucose 6-phosphate dehydrogenase or malate dehydrogenase activities. Our results suggest that DHEA may have decreased tumor nodule formation and reduced lipid peroxidation as previously reported, possibly by increasing the production of NADPH, a reducing equivalent for NADPH-dependent antioxidant enzymes. DHEA treatment tended to reduce glucose 6-phosphate dehydrogenase activities, which may have resulted in limited supply for de novo synthesis of DNA via inhibiting the hexose monophophaste pathway. Although both DHEA and vitamin E effectively reduced preneoplastic foci in this model, they seemed to fimction in different mechanisms. In conclusion, DHEA may be used to reduce hepatocellular carcinoma growth by targeting NADPH synthesis, cell proliferation and anti-oxidant enzyme activities during tumor growth.