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Anti-cancer effects of Phyllanthus urinaria and relevant mechanisms.
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James Offline
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Post: #1
Anti-cancer effects of Phyllanthus urinaria and relevant mechanisms.
Chang Gung Med J. 2010 Sep-Oct;33(5):477-87.

Anti-cancer effects of Phyllanthus urinaria and relevant mechanisms.

Huang ST, Pang JH, Yang RC.

Source

Department of Chinese Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan. shenteng@cgmh.org.tw

Abstract

Phyllanthus urinaria (P. urinaria), a widely used herbal medicine, has been reported to possess various biological activities. This report aimed to characterize the whole P. urinaria plant, present the anticancer effects of P. urinaria both in vivo and in vitro, and explore relevant mechanisms. The water extract of P. urinaria not only significantly reduces the cell viability of various cancer cell lines from different origins but also suppresses tumor development in C57BL/6J mice after implantation of Lewis lung carcinoma (LCC) cells. The anticancer activity of P. urinaria extract is mainly due to induced apoptosis of cancer cells as demonstrated by DNA fragmentation and increased caspase-3 activity through both intrinsic and extrinsic pathways. The decrease in viability with P. urinaria treatment might be partially associated with down-regulation of telomerase activation and induction of the apoptotic process. In addition, P. urinaria also exhibits anti-angiogenic activity that is mediated, at least in part, by suppression of matrix metalloproteinase 2 (MMP-2) secretion and inhibition of MMP-2 activity through zinc chelation.

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08-03-2012 07:08 AM
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James Offline
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Aqueous extract of Phyllanthus urinaria induces apoptosis in human cancer cells.
Am J Chin Med. 2004;32(2):175-83.

Aqueous extract of Phyllanthus urinaria induces apoptosis in human cancer cells.

Huang ST, Yang RC, Pang JH.

Source

Graduate Institute of Clinical Medical Sciences, Chang Gung University, Tao-Yuan, Taiwan.

Abstract

Cell apoptosis is now known to play an important role in the maintenance of cellular homeostasis and anti-carcinogenesis. The anticancer effect of aqueous extract prepared from Phyllanthus urinaria (P. urinaria) was investigated by analyzing its potential to induce apoptosis in human cancer cells. We showed that the aqueous extract of P. urinaria could reduce the viability by inducing the apoptosis in human cancer cells derived from several different origins as demonstrated by morphological changes and DNA fragmentation. Yet, P. urinaria extract exhibited no cytotoxic effect on normal human cells, including vascular endothelial cells and liver cells under the same conditions. It suggests that the aqueous extract of P. urinaria is substantially useful in treating various kinds of human cancer cells without toxic side effect on normal cells

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08-03-2012 07:10 AM
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James Offline
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Phyllanthus urinaria increases apoptosis and reduces telomerase activity in human nas
Forsch Komplementmed. 2009 Feb;16(1):34-40. Epub 2009 Feb 6.

Phyllanthus urinaria increases apoptosis and reduces telomerase activity in human nasopharyngeal carcinoma cells.

Huang ST, Wang CY, Yang RC, Chu CJ, Wu HT, Pang JH.

Source

Department of Chinese Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung Institute of Technology, Taiwan, Republic of China. sheng.teng@yahoo.com

Abstract

BACKGROUND:

This study was designed to obtain the chemical fingerprint and to investigate the effect of Phyllanthus urinaria on telomerase activity and apoptotic pathways in the human nasopharyngeal carcinoma cell line (NPC-BM1).

MATERIALS AND METHODS:

The polyphenol compounds in P. urinaria were investigated by HPLC/MS. Cell viability with the treatment of P. urinaria, gallic acid, ellagic acid, quercetin and cisplatin was detected by MTT assay. TUNEL assay, DNA fragmentation analysis and caspase3 activity were used to confirm apoptotic changes. Telomerase activity was determined using the TRAP assay. RNA isolation and RT-PCR were used to analyze the related genes expression. All experiments on treatments with P. urinaria from 0-3 mg/ml were carried out for 24 h.

RESULTS:

5 major compounds including gallic acid, brevifolin carboxylic acid, corilagin, phyllanthusiin C and ellagic acid were identified as a plant fingerprint by HPLC/MS. With the MTT assay, we demonstrated that P. urinaria, gallic acid and ellagic acid reduce cell viability. The apoptosis features showed DNA fragmentation and increased caspase-3 activity associated with the down-regulation of Bcl-2, but not of Bax, p53, and PCNA (proliferating cell nuclear antigen) in P. urinaria-treated NPC-BM1 cells. Furthermore, treatment of NPC-BM1 cells led to an inhibition of hTERT (human telomerase reverse transcriptase), hTP1 (human telomerase-associated protein 1) and c-myc mRNA expression and to decreased telomerase activity.

CONCLUSION:

This study suggests that P. urinaria induces the death of NPC-BM1 cells in vitro through the induction of apoptosis and inhibited telomerase activity.

Copyright © 2009 S. Karger AG, Basel.

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08-03-2012 07:11 AM
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James Offline
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Phyllanthus urinaria triggers the apoptosis and Bcl-2 down-regulation in Lewis lung c
Life Sci. 2003 Feb 28;72(15):1705-16.

Phyllanthus urinaria triggers the apoptosis and Bcl-2 down-regulation in Lewis lung carcinoma cells.

Huang ST, Yang RC, Yang LJ, Lee PN, Pang JH.

Source

Graduate Institute of Clinical Medical Sciences, Chang Gung University, Tao-Yuan, Taiwan, ROC.

Abstract

Phyllanthus urinaria (P. urinaria), a widely used herb medicine, was tested for the anticancer effect in its water extract for the first time. The water extract of P. urinaria significantly decreased the number of Lewis lung carcinoma cells in a dose-and time-dependent manner as determined by MTT assay. However, the water extract of P. urinaria did not exert any cytotoxic effect on normal cells such as endothelial cells and liver cells. Result from flow cytometry revealed a dose-dependent increase of dead cells 24 hours after treating Lewis lung carcinoma cells with P. urinaria extract. The anticancer activity of P. urinaria extract was due to the apoptosis induced in Lewis lung carcinoma cells, which was demonstrated by DNA fragmentation analysis and increased caspase-3 activity. The apoptosis triggered by P. urinaria extract in Lewis lung carcinoma cells was associated with the down-regulation of Bcl-2 gene expression, but not with p53, p21 and Bax. Furthermore, the partial inhibition of P. urinaria-induced apoptosis in Lewis lung carcinoma cells by pretreatment with cyclosporin A, a mitochondria permeability transition pore inhibitor, suggesting that P. urinaria extract induced the apoptosis of Lewis lung carcinoma cells, at least in part, through a mitochondria-associated intrinsic pathway.

Copyright 2002 Elsevier Science Inc.

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08-03-2012 07:13 AM
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James Offline
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Anti-tumor and anti-angiogenic effects of Phyllanthus urinaria in mice bearing Lewis
Int Immunopharmacol. 2006 Jun;6(6):870-9. Epub 2006 Jan 30.

Anti-tumor and anti-angiogenic effects of Phyllanthus urinaria in mice bearing Lewis lung carcinoma.

Huang ST, Yang RC, Lee PN, Yang SH, Liao SK, Chen TY, Pang JH.

Source

Graduate Institute of Clinical Medical Sciences, Chang Gung University, Tao-Yuan, Taiwan, ROC.

Abstract

Phyllanthus urinaria, a widely used herb medicine in Asia, was tested for its anti-tumor effect in vivo for the first time. The anti-tumor activity in P. urinaria extract was evaluated by its effect on tumor developed in C57BL/6J mice with implantation of Lewis lung carcinoma cells. The oral administration of P. urinaria to mice caused significant inhibition of tumor development with lower occurrence rate and markedly reduced tumor size. Neither the total body weight of mouse nor the weights of organs including heart, lung, liver, spleen and kidney revealed any difference between two groups, suggesting limited in vivo cytotoxic effect of P. urinaria in mice. TUNEL assay demonstrated the increase of apoptosis in tumor sections prepared from P. urinaria-treated mice compared with control mice. It is worth of note that the neovascularization in tumor was inhibited in P. urinaria-treated mice, which implicated the potential anti-angiogenic effect of P. urinaria. Further study using an in vitro matrix-induced tube formation of HUVECs again confirmed the anti-angiogenic action of P. urinaria. P. urinaria exerted no inhibitory effect on the growth of HUVECs, however, the migration of HUVECs as analyzed using transwell assay was suppressed markedly by P. urinaria in a dose-dependent manner. All together, the present study indicated that P. urinaria extract is an anti-tumor and anti-angiogenic agent, which can be used safely in animals.

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08-03-2012 07:14 AM
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James Offline
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Phyllanthus urinaria induces the Fas receptor/ligand expression and ceramide-mediated
Life Sci. 2004 Jun 4;75(3):339-51.

Phyllanthus urinaria induces the Fas receptor/ligand expression and ceramide-mediated apoptosis in HL-60 cells.

Huang ST, Yang RC, Chen MY, Pang JH.

Source

Chinese Herbal Pharmacy, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan, ROC.

Abstract

Phyllanthus urinaria (P. urinaria), a widely used herb medicine, was tested for the anticancer effect on human myeloid leukemia cells in this study. The water extract of P. urinaria induced the apoptosis of HL-60 cells as demonstrated by morphological change, DNA fragmentation and increased caspase-3 activity. However, normal human peripheral mononuclear cells remained viable under the same treatment. The P. urinaria-induced apoptosis of HL-60 cells was associated with the increased Bax gene expression and decreased Bcl-2 gene expression. In addition, the gene expressions of Fas receptor and Fas ligand, but not p53, were also induced in HL-60 cells dose- and time-dependently. The inhibitor of ceramide synthase, fumonisin B1, completely suppressed the apoptosis induced by P. urinaria and this inhibitory effect of fumonisin B1 could be eliminated by the addition of ceramide. It indicated that the activity of ceramide synthase is critical for the P. urinaria-induced apoptosis in HL-60 cells. The P. urinaria-induced apoptosis in HL-60 cells is mediated through a ceramide-related pathway.

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08-03-2012 07:16 AM
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James Offline
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Phyllanthus urinaria Induces Apoptosis in Human Osteosarcoma 143B Cells via Activatio
Evid Based Complement Alternat Med. 2012;2012:925824. Epub 2012 Feb 20.

Phyllanthus urinaria Induces Apoptosis in Human Osteosarcoma 143B Cells via Activation of Fas/FasL- and Mitochondria-Mediated Pathways.

Wu HY, Lin TK, Kuo HM, Huang YL, Liou CW, Wang PW, Chuang JH, Huang ST.

Source

Department of Chinese Medicine and Mitochondrial Research Unit, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan.

Abstract

Phyllanthus urinaria (P. urinaria), in this study, was used for the treatment of human osteosarcoma cells, which is one of the tough malignancies with few therapeutic modalities. Herein, we demonstrated that P. urinaria inhibited human osteosarcoma 143B cells growth through an apoptotic extrinsic pathway to activate Fas receptor/ligand expression. Both intracellular and mitochondrial reactive oxygen species were increased to lead to alterations of mitochondrial membrane permeability and Bcl-2 family including upregulation of Bid, tBid, and Bax and downregulation of Bcl-2. P. urinaria triggered an intrinsic pathway and amplified the caspase cascade to induce apoptosis of 143B cells. However, upregulation of both intracellular and mitochondrial reactive oxygen species and the sequential membrane potential change were less pronounced in the mitochondrial respiratory-defective 143Bρ(0) cells compared with the 143B cells. This study offers the evidence that mitochondria are essential for the anticancer mechanism induced by P. urinaria through both extrinsic and intrinsic pathways.

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http://www.ncbi.nlm.nih.gov/pmc/articles...ool=pubmed

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(This post was last modified: 08-03-2012 07:20 AM by James.)
08-03-2012 07:19 AM
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James Offline
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Phyllanthus spp. induces selective growth inhibition of PC-3 and MeWo human cancer ce
PLoS One. 2010 Sep 8;5(9):e12644.

Phyllanthus spp. induces selective growth inhibition of PC-3 and MeWo human cancer cells through modulation of cell cycle and induction of apoptosis.

Tang YQ, Jaganath IB, Sekaran SD.

Source

Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

Abstract

BACKGROUND:

Phyllanthus is a traditional medicinal plant that has been used in the treatment of many diseases including hepatitis and diabetes. The main aim of the present work was to investigate the potential cytotoxic effects of aqueous and methanolic extracts of four Phyllanthus species (P.amarus, P.niruri, P.urinaria and P.watsonii) against skin melanoma and prostate cancer cells.

METHODOLOGY/PRINCIPAL FINDINGS:

Phyllanthus plant appears to possess cytotoxic properties with half-maximal inhibitory concentration (IC(50)) values of 150-300 µg/ml for aqueous extract and 50-150 µg/ml for methanolic extract that were determined using the MTS reduction assay. In comparison, the plant extracts did not show any significant cytotoxicity on normal human skin (CCD-1127Sk) and prostate (RWPE-1) cells. The extracts appeared to act by causing the formation of a clear "ladder" fragmentation of apoptotic DNA on agarose gel, displayed TUNEL-positive cells with an elevation of caspase-3 and -7 activities. The Lactate Dehydrogenase (LDH) level was lower than 15% in Phyllanthus treated-cancer cells. These indicate that Phyllanthus extracts have the ability to induce apoptosis with minimal necrotic effects. Furthermore, cell cycle analysis revealed that Phyllanthus induced a Go/G1-phase arrest on PC-3 cells and a S-phase arrest on MeWo cells and these were accompanied by accumulation of cells in the Sub-G1 (apoptosis) phase. The cytotoxic properties may be due to the presence of polyphenol compounds such as ellagitannins, gallotannins, flavonoids and phenolic acids found both in the water and methanol extract of the plants.

CONCLUSIONS/SIGNIFICANCE:

Phyllanthus plant exerts its growth inhibition effect in a selective manner towards cancer cells through the modulation of cell cycle and induction of apoptosis via caspases activation in melanoma and prostate cancer cells. Hence, Phyllanthus may be sourced for the development of a potent apoptosis-inducing anticancer agent.

Full text:

http://www.ncbi.nlm.nih.gov/pmc/articles...ool=pubmed

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08-03-2012 07:22 AM
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James Offline
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Phyllanthus amarus inhibits cell growth and induces apoptosis in Dalton's lymphoma as
Integr Cancer Ther. 2009 Jun;8(2):190-4. Epub 2009 Feb 17.

Phyllanthus amarus inhibits cell growth and induces apoptosis in Dalton's lymphoma ascites cells through activation of caspase-3 and downregulation of Bcl-2.

Harikumar KB, Kuttan G, Kuttan R.

Source

Amala Cancer Research Centre, Amala Nagar, Thrissur, Kerala, India. kbharikumar@gmail .com

Abstract

The authors found in an earlier study that Phyllanthus amarus extract could significantly inhibit the solid and ascites tumor development in mice induced by Dalton's lymphoma ascites (DLA) cells. In the present study, the apoptotic effects of P. amarus against DLA cells in culture was evaluated. P. amarus produced significant reduction in cell viability as determined by the MTT assay. It also induces the formation of apoptotic bodies with characteristic features like plasma membrane invagination, elongation, fragmentation, and chromatin condensation. P. amarus at concentrations of 100 and 200 microg/mL is shown to induce DNA fragmentation. Gene expression analysis reveals that P. amarus induces the expression of caspase-3 and inhibits the expression of Bcl-2, which is an antiapoptotic protein. So the present study provides some insights into the possible mechanism by which P. amarus brings about apoptosis and growth inhibition in DLA cells.

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08-03-2012 07:23 AM
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Antitumour and anticarcinogenic activity of Phyllanthus amarus extract.
J Ethnopharmacol. 2002 Jun;81(1):17-22.

Antitumour and anticarcinogenic activity of Phyllanthus amarus extract.

Rajeshkumar NV, Joy KL, Kuttan G, Ramsewak RS, Nair MG, Kuttan R.

Source

Amala Cancer Research Centre, Thrissur, Kerala, 680-553, India.

Abstract

Aqueous extract of Phyllanthus amarus (P. amarus) treatment exhibited potent anticarcinogenic activity against 20-methylcholanthrene (20-MC) induced sarcoma development and increased the survival of tumour harboring mice. The extract administration (p.o) was also found to prolong the life span of Dalton's Lymphoma Ascites (DLA) and Ehrlich Ascites Carcinoma (EAC) bearing mice and reduced the volume of transplanted solid tumours. The extract inhibited aniline hydroxylase, a P-450 enzyme. The concentration required for 50% inhibition (IC(50)) was found to be 540 microg/ml. The extract was found to inhibit DNA topoisomerase II of Saccharomyces cerevisiae mutant cell cultures and inhibited cell cycle regulatory enzyme cdc25 tyrosine phosphatase (IC(50-25) microg/ml). Antitumour and anticancer activity of P. amarus may be related with the inhibition of metabolic activation of carcinogen as well as the inhibition of cell cycle regulators and DNA repair.

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08-03-2012 07:25 AM
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RE: Anti-cancer effects of Phyllanthus urinaria and relevant mechanisms.
A normal diet of uncontaminated natural vegetables and natural fruits for the lots of omega-3's and healthy nourishment has been confirmed to be successful in several normal anti-cancer methods.
08-30-2012 04:07 PM
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