The purpose of this site is to collect lab research by medical doctors about herbs that are proven to treat illnesses and counter the false attacks on herbs by the medical industry and false claims by alternative medicine. I let the science tell the facts.
index sitemap advanced
search engine by freefind
Milk Thistle - Silymarian Date Written 6-20-09
Author Joe Holmes Date Revised  

I repeatedly referr to Metabolic Stress as the foundation of all disease especialy diabetes report 4 mentions this and its effect on diabetes with a human double blind test showing Milk Thistle improves both diabetes, colesterol and metabolic stress.


1. "Milk thistles are thistles of the genus Silybum Adans., flowering plants of the daisy family (Asteraceae). They are native to the Mediterranean regions of Europe, North Africa and the Middle East. The name "milk thistle" derives from two features of the leaves: they are mottled with splashes of white and they contain a milky sap.[1] However, it is the seeds of milk thistle that herbalists have used for 2000 years to treat chronic liver disease and protect the liver against toxins.[2][3] Increasing research is being undertaken on the physiological effects, therapeutic properties and possible medical uses of milk thistle. [4] (1)

2. " Review of clinical trials evaluating safety and efficacy of milk thistle (Silybum marianum [L.] Gaertn.).
Tamayo C, Diamond S. Research and Development at Flora Inc, Bethesda, MD 20817, USA.

Milk thistle extracts have been used as traditional herbal remedies for almost 2000 years. The extracts are still widely used to protect the liver against toxins and to control chronic liver diseases. Recent experimental and clinical studies suggest that milk thistle extracts also have anticancer, antidiabetic, and cardioprotective effects. This article reviews clinical trials of milk thistle conducted in the past 5 years including pharmacokinetic and toxicity studies, herb-drug interactions, and other safety issues. Several trials have studied the effects of milk thistle for patients with liver diseases, cancer, hepatitis C, HIV, diabetes, and hypercholesterolemia. Promising results have been reported in the protective effect of milk thistle in certain types of cancer, and ongoing trials will provide more evidence about this effect. In addition, new established doses and improvement on the quality and standardization of this herb will provide the much-awaited evidence about the efficacy of milk thistle in the treatment of liver diseases. Milk thistle extracts are known to be safe and well tolerated, and toxic or adverse effects observed in the reviewed clinical trials seem to be minimal. The future of milk thistle research is promising, and high-quality randomized clinical trials on milk thistle versus placebo may be needed to further demonstrate the safety and efficacy of this herb. PMID: 17548793 (2)

4. The efficacy of Silybum marianum (L.) Gaertn. (silymarin) in the treatment of type II diabetes: a randomized, double-blind, placebo-controlled, clinical trial. Huseini HF, Larijani B, Heshmat R, Fakhrzadeh H, Radjabipour B, Toliat T, Raza M. Department of Pharmacology, Institute of Medicinal Plants, ACECR Tehran, Iran.

Oxidative stresses are increasingly implicated in the pathogenesis of diabetic complications which may either cause direct pancreatic beta-cell damage or lead to metabolic abnormalities that can induce or aggravate diabetes. The valuable effect of antioxidant nutrients on the glycemic control of diabetic patients has been reported in experimental and clinical studies. The present study was designed to investigate the effects of the herbal medicine, Silybum marianum seed extract (silymarin), which is known to have antioxidant properties on the glycemic profile in diabetic patients. A 4-month randomized double-blind clinical trial was conducted in 51 type II diabetic patients in two well-matched groups. The first group (n = 25) received a silymarin (200 mg) tablet 3 times a day plus conventional therapy. The second group (n = 26) received the same therapy but a placebo tablet instead of silymarin. The patients were visited monthly and glycosylated hemoglobin (HbA(1)c), fasting blood glucose (FBS), insulin, total cholesterol, LDL and HDL, triglyceride, SGOT and SGPT levels were determined at the beginning and the end of the study. The results showed a significant decrease in HbA(1)c, FBS, total cholesterol, LDL, triglyceride SGOT and SGPT levels in silymarin treated patients compared with placebo as well as with values at the beginning of the study in each group. In conclusion, silymarin treatment in type II diabetic patients for 4 months has a beneficial effect on improving the glycemic profile. PMID: 17072885 (3)


1. Cancer Lett. 2004 Nov 25;215(2):129-40. Role of chemopreventive agents in cancer therapy. Dorai T, Aggarwal BB.
Comprehensive Cancer Center, Our Lady of Mercy Medical Center, New York Medical College, Bronx, NY 10466, USA.

Tumorigenesis or carcinogenesis is a multi-step process that is induced primarily by carcinogens leading to the development of cancer. Extensive research in the last few years has revealed that regular consumption of certain fruits and vegetables can reduce the risk of acquiring specific cancers. Phytochemicals derived from such fruits and vegetables, referred to as chemopreventive agents include genistein, resveratrol, diallyl sulfide, S-allyl cysteine, allicin, lycopene, capsaicin, curcumin, 6-gingerol, ellagic acid, ursolic acid, silymarin, anethol, catechins and eugenol. Because these agents have been shown to suppress cancer cell proliferation, inhibit growth factor signaling pathways, induce apoptosis, inhibit NF-kappaB, AP-1 and JAK-STAT activation pathways, inhibit angiogenesis, suppress the expression of anti-apoptotic proteins, inhibit cyclooxygenase-2, they may have untapped therapeutic value. These chemopreventive agents also have very recently been found to reverse chemoresistance and radioresistance in patients undergoing cancer treatment. Thus, these chemopreventive agents have potential to be used as adjuncts to current cancer therapies.
PMID: 15488631

2. Cancer Res. 2004 Sep 1;64(17):6349-56. Silibinin protects against photocarcinogenesis via modulation of cell cycle regulators, mitogen-activated protein kinases, and Akt signaling. Mallikarjuna G, Dhanalakshmi S, Singh RP, Agarwal C, Agarwal R. Department of Pharmaceutical Sciences, School of Pharmacy, and University of Colorado Cancer Center, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.

Here, we assessed the protective effect of silibinin on UVB-induced skin carcinogenesis in SKH-1 hairless mice. Topical application of silibinin before or immediately after UVB exposure or its dietary feeding resulted in a strong protection against photocarcinogenesis, in terms of tumor multiplicity (60-66%; P < 0.001), tumor volume per mouse (93-97%; P < 0.001) and tumor volume per tumor (80-91%; P < 0.001). Silibinin also moderately inhibited tumor incidence (5-15%; P < 0.01) and delayed tumor latency period (up to 4 weeks; P < 0.01-0.001). To investigate in vivo molecular mechanisms of silibinin efficacy, tumors and uninvolved skin from tumor-bearing mice were examined immunohistochemically for proliferation, p53, apoptosis, and activated caspase-3. Silibinin treatment showed a strong decrease (P < 0.001) in proliferating cell nuclear antigen-positive cells and an increase in p53-positive (P < 0.005-0.001), terminal deoxynucleotidyltransferase-mediated nick end labeling-positive (P < 0.005-0.001), and cleaved caspase-3-positive cells (P < 0.001). Western blot analysis of normal skin and tumor lysates showed that silibinin decreases the levels of cyclin-dependent kinase 2 and cyclin-dependent kinase 4 and associated cyclins A, E, and D1, together with an up-regulation of Cip1/p21, Kip1/p27, and p53. Silibinin also showed a strong phosphorylation of extracellular signal-regulated protein kinase 1/2, stress-activated protein kinase/c-JUN NH2-terminal kinase 1/2, and p38 mitogen-activated protein kinases but inhibited Akt phosphorylation and decreased survivin levels with an increase in cleaved caspase-3. Together, these results show a strong preventive efficacy of silibinin against photocarcinogenesis, which involves the inhibition of DNA synthesis, cell proliferation, and cell cycle progression and an induction of apoptosis. Furthermore, these results also identify in vivo molecular mechanisms of silibinin efficacy against photocarcinogenesis. PMID: 15342425

3: Pharm Res. 2004 Jul;21(7):1263-73. Combined effects of multiple flavonoids on breast cancer resistance protein (ABCG2)-mediated transport. Zhang S, Yang X, Morris ME. Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical
Sciences, University at Buffalo, State University of New York, Amherst, New York 14260, USA.

PURPOSE: The purpose of this study was to determine the dynamic parameter (EC50) of flavonoids apigenin, biochanin A, chrysin, genistein, kaempferol, hesperetin, naringenin, and silymarin for breast cancer resistance protein (BCRP) inhibition when used alone, and to evaluate their potential interactions (additive, synergistic, or antagonistic) with regards to BCRP inhibition when used in multiple-flavonoid combinations. METHODS: The effects of flavonoids on BCRP-mediated transport were examined by evaluating their effects on mitoxantrone accumulation and cytotoxicity in MCF-7 MX100 cells overexpressing BCRP. The EC50 values of these flavonoids for increasing mitoxantrone accumulation were estimated using a Hill equation. The potential interactions among multiple flavonoids with regard to BCRP inhibition were assessed by isobologram and Berenbaum's interaction index methods. RESULTS: The EC50 values of these flavonoids for increasing mitoxantrone accumulation ranged from 0.39+/-0.13 microM to 33.7+/-2.78 microM. Quantitative analysis of the combined effects of multiple flavonoids on mitoxantrone accumulation indicated that these flavonoids act additively in inhibiting BCRP when given as 2-, 3-, 5-, or 8-flavonoid combinations with equimolar concentrations of all constituents. The results of the mitoxantrone cytotoxicity studies were consistent with these findings. CONCLUSIONS: The additive effects of multiple flavonoids for BCRP inhibition suggests that prediction of BCRP-mediated food (herbal product)-drug interactions should also take into consideration the presence of multiple flavonoids and provides a rationale for using "flavonoid cocktails" as a potential approach for multidrug resistance reversal in cancer treatment. PMID: 15290869

4: Planta Med. 2004 May;70(5):397-400. Silibinin down-regulates prostate epithelium-derived Ets transcription factor in LNCaP prostate cancer cells. Thelen P, Jarry H, Ringert RH, Wuttke W. Department of Urology, Georg-August-University, Gottingen, Germany.

The androgen-sensitive human prostate cancer cell line LNCaP expresses the estrogen receptor beta and androgen receptor and can be stimulated by androgens to secrete prostate-specific antigen (PSA). In this study we demonstrate the cancer protective potential of silibinin, a flavolignan derived from the fruits of Silybum marianum, which down-regulates the co-activator of the androgen receptor, the prostate epithelium-derived Ets transcription factor (PDEF) and consequently the secretion of PSA. LNCaP cells were treated with various concentrations of silibinin in the presence or in the absence of 5alpha-dihydrotestosterone (DHT). We used real-time RT-PCR to quantify mRNA expression of PDEF and PSA with gene-specific dual-labelled fluorescence probes. PSA secretion from LNCaP cells in conditioned media was measured with the Elecsys System 2010. Silibinin down-regulated PSA mRNA expression and PSA secretion in conditioned medium under basal and DHT (10(-8) M) stimulated conditions, which was paralleled by PDEF down-regulation. DHT alone stimulated PDEF and PSA gene expression and PSA secretion. The down-regulation of basal as well as DHT stimulated PDEF and PSA by silibinin demonstrates the antiproliferative potential of this agent. These effects underline the possible therapeutic use of silibinin in the management of prostate cancer. PMID: 15124082

5: J Urol. 2004 May;171(5):1934-8. Inhibition of telomerase activity and secretion of prostate specific antigen by silibinin in prostate cancer cells. Thelen P, Wuttke W, Jarry H, Grzmil M, Ringert RH. Department of Urology, Institute of Human Genetics, Georg-August-University, Gottingen, Germany.

PURPOSE: The androgen sensitive prostate cancer cell line LNCaP is strongly positive for dihydrotestosterone (DHT) dependent telomerase activity, which is an important factor in cellular immortality and carcinogenesis. In this study we determined the potential of silibinin as an anticancer drug that down-regulates telomerase activity and prostate specific antigen (PSA) together with the co-activator of the androgen receptor prostate epithelium specific Ets transcription factor. MATERIALS AND METHODS: LNCaP cells were treated with various concentrations of silibinin in the presence or absence of 5alpha-DHT. We used real-time reverse transcriptase-polymerase chain reaction to quantify mRNA expression of PSA, prostate epithelium specific Ets transcription factor and the catalytic subunit of telomerase vs the housekeeping gene porphobilinogen deaminase with gene specific, dual labeled fluorescence probes. PSA secretion from LNCaP cells in conditioned medium was measured with an Elecsys System 2010 (Roche Diagnostics, Mannheim, Germany) and telomerase activity in extracts from LNCaP cells was measured with a TRAP (telomeric repeat amplification protocol) assay. RESULTS: Silibinin down-regulated PSA mRNA expression and PSA secretion in conditioned medium. Simultaneous stimulation with silibinin and 10(-8) M DHT also resulted in PSA down-regulation, whereas DHT alone increased PSA secretion. Telomerase catalytic subunit mRNA decreased significantly after silibinin stimulation. Telomerase activity was down-regulated by silibinin and stimulated by DHT. The 2 agents in combination resulted in telomerase down-regulation.

CONCLUSIONS: The down-regulation of PSA by silibinin and its counteraction on DHT effects indicate that this compound can interact with the expression of genes that are regulated through the androgen receptor. Silibinin can also inhibit the telomerase activity that mediates cell immortality and carcinogenesis. The 2 effects underline the possible therapeutic use of silibinin as an antiproliferative gent in intervention for prostate cancer. PMID: 15076315

6: Curr Cancer Drug Targets. 2004 Feb;4(1):1-11. Prostate cancer prevention by silibinin. Singh RP, Agarwal R. Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Cancer Center, 4200 East Ninth Avenue, Denver, CO 80262, USA.

Several epigenetic alterations leading to constitutively active mitogenic and cell-survival signaling, and loss of apoptotic response are causally involved in self-sufficiency of prostate cancer (PCA) cells toward uncontrolled growth, and increased secretion of pro-angiogenic factors. Therefore, one targeted approach for PCA prevention, growth control and/or treatment could be inhibition of epigenetic molecular events involved in PCA growth, progression and angiogenesis. In this regard, silibinin/silymarin (silibinin is the major active compound in silymarin) has shown promising efficacy. Our extensive studies with silibinin/silymarin and PCA cells have shown the pleiotropic anticancer effects leading to cell growth inhibition in culture and nude mice. The underlying mechanisms of silibinin/silymarin efficacy against PCA involve alteration in cell cycle progression, and inhibition of mitogenic and cell survival signaling, such as epidermal growth factor receptor, insulin-like growth factor receptor type I and nuclear factor kappa B signaling. Silibinin also synergizes the therapeutic effects of doxorubicin in PCA cells, making it a strong candidate for combination chemotherapy. Silibinin/ silymarin also inhibits the secretion of proangiogenic factors from tumor cells, and causes growth inhibition and apoptotic death of endothelial cells accompanied by disruption of capillary tube formation on Matrigel. More importantly, silibinin inhibits the growth of in vivo advanced human prostate tumor xenograft in nude mice. Recently, due to its non-toxic and mechanism-based strong preventive/therapeutic efficacy, silibinin has entered in phase I clinical trial in prostate cancer patients.
Publication Types: Review Review, Academic PMID: 14965263

7: Int J Mol Med. 2004 Jan;13(1):81-6. Involvement of NF-kappaB and caspases in silibinin-induced apoptosis of endothelial cells. Yoo HG, Jung SN, Hwang YS, Park JS, Kim MH, Jeong M, Ahn SJ, Ahn BW, Shin BA, Park RK, Jung YD.
Chonnam University Research Institute of Medical Sciences, Chonnam National University Medical School, Kwangju, Korea.

Silibinin, the flavonoid found in the milk thistle, has been shown to suppress cell growth and exhibit anti-cancer effects. Some flavonoids were reported to inhibit angiogenesis which is essential for tumor growth and metastasis. In this study, to clarify the underlying mechanisms for the anti-cancer effect of silibinin, we examined the effects of silibinin on human endothelial ECV304 cells. Silibinin was found to suppress the growth and induce the apoptosis of ECV304 cells. The induction of apoptosis by silibinin was confirmed by ladder-patterned DNA fragmentation, cleaved and condensed nuclear chromatin and DNA hypoploidy. Silibinin could effectively inhibit constitutive NF-kappaB activation as revealed by electrophoretic mobility shift assay and NF-kappaB-dependent luciferase reporter study. Consistent with this, silibinin treatment resulted in a significant decrease in the nuclear level of p65 subunit of NF-kappaB. In addition, silibinin treatment caused a change in the ratio of Bax/Bcl-2 in a manner that favors apoptosis. Silibinin also induced the cytochrome c release, activation of caspase-3 and caspase-9 and cleavage of PARP. These results suggest that silibinin may exert, at least partly, its anti-cancer effect by inhibiting angiogenesis through induction of endothelial apoptosis via modulation of NF-kappaB, Bcl-2 family and caspases. PMID: 14654975

8: Biochem Biophys Res Commun. 2003 Dec 26;312(4):1178-84. Silibinin down-regulates survivin protein and mRNA expression and causes caspases activation and apoptosis in human bladder transitional-cell papilloma RT4 cells. Tyagi AK, Agarwal C, Singh RP, Shroyer KR, Glode LM, Agarwal R. Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Health Sciences Center, Denver, CO 80262, USA.

Bladder cancer is the fourth and eighth most common cancer in men and women in the United States, respectively. Survivin, a member of inhibitor of apoptosis protein (IAP) gene family, is deregulated in a wide range of malignancies, including carcinoma of the bladder urothelium. Recent advances have identified survivin as a novel intervention target to induce apoptosis in cancer cells by phytochemicals or synthetic agents. Silibinin is a naturally occurring flavanone, isolated from milk thistle extract, and has been shown to possess cancer prevention/intervention potential against various cancers. In several animal and human studies, it is found to be safe and non-toxic. Human bladder transitional-cell papilloma RT4 cells were treated with silibinin and analyzed for survivin protein and mRNA levels by Western blotting and real-time RT-PCR, respectively. Silibinin treatment of cells for 24 h at 100 microM dose resulted in approximately 50% decrease in survivin protein level; however, treatment at 200 microM dose for 24 and 48 h showed a complete loss in survivin protein without any change in actin used as loading control. Employing RT-PCR analysis we also observed that silibinin causes a strong to complete decrease in survivin mRNA levels. In other studies, down-regulation of survivin by silibinin was associated with a very strong and prominent caspases-9 and -3 activation as well as PARP cleavage. Quantitative apoptotic assay showed that silibinin decreased survivin levels and caspases-PARP cleavages, in accord with a strong apoptotic death and growth inhibition of RT4 cells. Together, these findings suggest that more studies are needed to investigate in vivo effect of silibinin on survivin expression and associated biological effects in bladder cancer that could provide useful information for silibinin efficacy in the prevention/intervention of human bladder cancer. PMID: 14651997

9: Oncogene. 2003 Nov 13;22(51):8271-82. Silibinin upregulates the expression of cyclin-dependent kinase inhibitors and causes cell cycle arrest and apoptosis in human colon carcinoma HT-29 cells. Agarwal C, Singh RP, Dhanalakshmi S, Tyagi AK, Tecklenburg M, Sclafani RA, Agarwal R. Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Health Sciences Center, Denver, CO 80262, USA.

Silymarin, a defined mixture of natural flavonoid, has recently been shown to have potent cancer chemopreventive efficacy against colon carcinogenesis in rat model; however, the mechanism of such efficacy is not elucidated. Here, using pure active agent in silymarin, namely silibinin, we show its antiproliferative and apoptotic effects, and associated molecular alterations in human colon carcinoma HT-29 cells. Silibinin treatment of cells at 50-100 microg/ml doses resulted in a moderate to very strong growth inhibition in a dose- and a time-dependent manner, which was largely due to a G0/G1 arrest in cell cycle progression; higher dose and longer treatment time also caused a G2/M arrest. In mechanistic studies related its effect on cell cycle progression, silibinin treatment resulted in an upregulation of Kip1/p27 and Cip1/p21 protein as well as mRNA levels, and decreased CDK2, CDK4, cyclin E and cyclin D1 protein levels together with an inhibition in CDK2 and CDK4 kinase activities. In other studies, we observed that G2/M arrest by silibinin was associated with a decrease in cdc25C, cdc2/p34 and cyclin B1 protein levels, as well as cdc2/p34 kinase activity. In the studies assessing biological fate of silibinin-treated cells, silibinin-induced cell cycle arrest and growth inhibition were not associated with cellular differentiation, but caused apoptotic death. The quantitative apoptosis analysis showed up to 15% apoptotic cell death after 48 h of silibinin treatment. Interestingly, silibinin-induced apoptosis in HT-29 cells was independent of caspases activation, as all caspases inhibitor did not reverse silibinin-induced apoptosis. This observation was further confirmed by the findings showing a lack in caspases activity increase and caspases and PARP cleavage as well as a lack in cytochrome c release in cytosol following silibinin treatment of HT-29 cells. Additional studies conducted in mice showed that silibinin doses found effective in HT-29 cells are achievable in plasma, which increases the significance of the present findings and their possible translation in in vivo anticancer efficacy of silibinin against colon cancer. Together, these results identify molecular mechanisms of silibinin efficacy as a cell cycle regulator and apoptosis inducer in human colon carcinoma HT-29 cells, and justify further studies to investigate potential usefulness of this nontoxic agent in colon cancer prevention and intervention. PMID: 14614451

10: Cancer Biol Ther. 2003 Sep-Oct;2(5):526-31. Comment in: Cancer Biol Ther. 2003 Sep-Oct;2(5):532-3.
Epidermal growth factor receptor mediates silibinin-induced cytotoxicity in a rat glioma cell line. Qi L, Singh RP, Lu Y, Agarwal R, Harrison GS, Franzusoff A, Glode LM. Department of Medicine, University of Colorado Health Sciences Center; Denver, Colorado USA.

Silibinin, derived from milk thistle extract, has been shown to inhibit growth factor receptor-mediated mitogenic and cell survival signaling, and to alter cell cycle regulators. Alteration in pathways regulating cell growth likely account for silibinin's inhibition of tumor growth. Since the epidermal growth factor receptor (EGFR) is a key regulator in cell signaling pathways, in the present study we directly tested the hypothesis that the EGFR plays a key role in mediating silibinin cytotoxicity to cancer cells. We generated a cell line, 9L-EGFR, which stably expressed human EGFR; the parental rat glioma cell line, 9L, does not contain endogenous EGFR message or protein. Our results show that expression of EGFR was both necessary and sufficient for conferring toxicity in response to silibinin in 9L-EGFR cells. Addition of silibinin was shown to inhibit EGFR activation by EGF in 9L-EGFR cells. These studies support the hypothesis that silibinin toxicity to cancer cells involves the EGFR signaling pathway. The findings presented here provide a rationale for understanding the growth inhibition effect of silibinin in cancer cells, and warrant further investigation into the effect of silibinin on specific pathways of cell signaling mediated by the EGF receptor.PMID: 14614320

11: Eur J Cancer. 2003 Nov;39(16):2403-10. Antitumour activity of the silybin-phosphatidylcholine complex, IdB 1016, against human ovarian cancer. Gallo D, Giacomelli S, Ferlini C, Raspaglio G, Apollonio P, Prislei S, Riva A, Morazzoni P, Bombardelli E, Scambia G. Department of Obstetrics and Gynaecology, Catholic University of the Sacred Heart, Lgo A. Gemelli, 8-00168, Rome, Italy.

This study aimed to assess, in an in vivo experimental model, the growth inhibitory effects of IdB 1016 (Silipide, a complex of silybin/phosphatidylcholine) when used as a single agent against human ovarian cancer. We also wanted to investigate the mechanism of the antiangiogenic action by assessing Vascular Endothelial Growth Factor (VEGF) levels and by using macroarray technology to evaluate the regulation of a panel of genes involved in angiogenesis. We also aimed to establish the plasma and tumour bioavailability of silybin after repeated administration of IdB 1016. Female nude mice bearing human ovarian cancer xenografts (A2780) received 450 mg/kg/day IdB 1016 daily by oral gavage until the end of the study. At sacrifice, blood and tumour specimens were collected and subsequently processed for the determination of silybin levels, VEGF levels or a gene expression profile. IdB 1016 was significantly active in inhibiting ovarian tumour growth. Treatment with 450 mg/kg/day for a total of 20 administrations produced a tumour weight inhibition (TWI%) of 78% and a Log10 Cell Kill (LCK) of 1.1. Free silybin levels were found to be 7.0+/-5.3 microg/ml and 183.5+/-85.9 ng/g tissue (mean+/-standard deviation (S.D.)) in the plasma and tumour samples, respectively. No significant differences were found in the concentration of human VEGF in xenografts from control and IdB 1016-treated mice. The array analysis suggested the downregulation of the VEGR receptor 3 and the upregulation of angiopoietin-2 as potential mechanisms for the antiangiogenic activity. In conclusion, these findings suggest IdB 1016 is a good candidate, with a relevant clinical potential, for use in the management of recurrent ovarian cancer. A phase II, non-randomised clinical study is now ongoing in our Institute aimed at evaluating the efficacy of daily administrations of IdB 1016 in the serological recurrence of ovarian cancer. PMID: 14556934

12: Cancer Epidemiol Biomarkers Prev. 2003 Sep;12(9):933-9. Suppression of advanced human prostate tumor growth in athymic mice by silibinin feeding is associated with reduced cell proliferation, increased apoptosis, and inhibition of angiogenesis.
Singh RP, Sharma G, Dhanalakshmi S, Agarwal C, Agarwal R. Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.

Recently, we observed that dietary feeding of silibinin strongly prevents and inhibits the growth of advanced human prostate tumor xenografts in athymic nude mice without any apparent signs of toxicity together with increased secretion of insulin-like growth factor-binding protein 3 from the tumor in to mouse plasma (R. P. Singh et al., Cancer Res., 62:3063-3069, 2002). In the present study, we investigated the effect of silibinin feeding [0.05% and 0.1% (w/w) in diet for 60 days] on the prognostic biomarkers (namely, proliferation, apoptosis, and angiogenesis) in the prostate tumor xenografts of the above-reported study. Immunohistochemical analysis of the tumors for proliferating cell nuclear antigen and Ki-67 showed that silibinin decreases proliferation index by 28-60% and 30-60% (P<0.001) as compared with their controls, respectively. In situ detection of apoptosis by terminal deoxynucleotidyl transferase dUTP-mediated nick end labeling staining of tumors showed a 7.4-8.1-fold (P<0.001) increase in apoptotic cells in silibinin-fed groups over that of control group. Silibinin also increased activated caspase 3-positive cells by 2.3-3.6-fold (P<0.001). CD31 staining for tumor vasculature showed a significant decrease (21-38%; P<0.001) in tumor microvessel density in silibinin-fed groups of tumors as compared with control group of tumors. Tumor sections were also analyzed for vascular endothelial growth factor and insulin-like growth factor-binding protein 3 protein expression, and a slightly decreased and a moderately increased cytoplasmic immunostaining in silibinin-fed groups were observed as compared with the control group, respectively. Together, these results suggest that inhibition of advanced human prostate tumor xenograft growth in athymic nude mice by silibinin is associated with its in vivo antiproliferative, proapoptotic, and antiangiogenic efficacy in prostate tumor. PMID: 14504208

PMID: 12943822
PMID: 12894553
PMID: 12429923
PMID: 12386921
PMID: 11896607
PMID: 11006131


2 PMID: 17548793
3 PMID: 17072885
4 PMID: 17072885



Recommended Information