nach oben

Journal of Cancer Research and Clinical Oncology

Erschienen in:

01.12.2009 | Original Paper

Gambogic acid reduced bcl-2 expression via p53 in human breast MCF-7 cancer cells

verfasst von: Hongyan Gu, Shuyun Rao, Jie Zhao, Jia Wang, Rong Mu, Jingjing Rong, Lei Tao, Qi Qi, Qidong You, Qinglong Guo

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 12/2009

Einloggen, um Zugang zu erhalten

Abstract

Purpose

In this study, we investigated the correlation between p53 and bcl-2 in gambogic acid (GA)-induced apoptosis.

Method

MTT assay was employed to evaluate MCF-7 cell viability after GA treatment. Cell morphological changes were observed follow-up under the inverted microscope after GA withdrawal. To observe the cell apoptosis, DAPI staining was used. Meanwhile, p53 small interfering RNA (si-RNA) was adopted to knock p53 down. All expressions of p53 and bcl-2 were evaluated by Western blot analysis.

Results

MTT assay showed that GA inhibited MCF-7 cell growth effectively in a time-dependent manner. With 0.5 h GA treatment, p53 was significantly increased, whereas bcl-2 was reduced potently with 6 h GA treatment. After GA withdrawal, p53 expressions were maintained in high levels. Furthermore, bcl-2 decreasing was attenuated after co-treatment with PFT alpha, a p53 transcription blocker. Same result was observed after p53 knock-down by p53 si-RNA.

Conclusions

Gambogic acid induced human breast cancer cells MCF-7 apoptosis by reducing bcl-2 expression via p53.

Nur mit Berechtigung zugänglich

Cumming G, Fidler F, Vaux DL (2007) Error bars in experimental biology. J Cell Biol 177:7–11. doi:10.1083/jcb.200611141 PubMedCrossRef

Gu H, Guo Q (2007) The advanced developments of P53. J Int Oncol 34(11):801–803

Gu H, Wang X, Rao S, Wang J, Zhao J, Ren FL et al (2008a) Gambogic acid mediates apoptosis as a P53 inducer through down-regulation of Mdm2 in wild-type P53-expressing cancer cells. Mol Cancer Ther 7:3298–3305. doi:10.1158/1535-7163.MCT-08-0212 PubMedCrossRef

Gu H, You Q, Liu W, Yang Y, Zhao L, Qi Q et al (2008b) Gambogic acid induced tumor cell apoptosis by T lymphocyte activation in H22 transplanted mice. Int Immunopharmacol 8:1493–1502. doi:10.1016/j.intimp.2008.05.013 PubMedCrossRef

Guo Q, Qi Q, You Q, Gu H, Zhao L, Wu Z (2006) Toxicological studies of gambogic acid and its potential targets in experimental animals. Basic Clin Pharmacol Toxicol 99:178–184. doi:10.1111/j.1742-7843.2006.pto_485.x PubMedCrossRef

Kasibhatla S, Jessen KA, Maliartchouk S, Wang JY, English NM, Drewe J et al (2005) A role for transferrin receptor in triggering apoptosis when targeted with gambogic acid. Proc Natl Acad Sci USA 102:12095–12100. doi:10.1073/pnas.0406731102 PubMedCrossRef

Li M, Brooks CL, Wu-Baer F, Chen D, Baer R, Gu W (2003) Mono-versus polyubiquitination: differential control of P53 fate by Mdm2. Science 302:1972–1975. doi:10.1126/science.1091362 PubMedCrossRef

Liu WY, Feng F, You QD, Zhang ZH (2003) The assessment of gambogic acid content in total gambogic acid by Rp-Hplc assay. Chin Tradit Herbal Drugs 34:706–707

Liu W, Feng F, You Q, Zhang ZX (2004a) The improvement on contents measurement of gambogic acid injection. Traditional Patent Medicine 26:add 8–9

Liu X, Chua CC, Gao J, Chen Z, Landy CL, Hamdy R et al (2004b) Pifithrin-alpha protects against doxorubicin-induced apoptosis and acute cardiotoxicity in mice. Am J Physiol Heart Circ Physiol 286:H933–H939. doi:10.1152/ajpheart.00759.2003 PubMedCrossRef

Liu W, Guo QL, You QD, Zhao L, Gu HY, Yuan ST (2005) Anticancer effect and apoptosis induction of gambogic acid in human gastric cancer line Bgc-823. World J Gastroenterol 11:3655–3659PubMed

Lu N, Yang Y, You QD, Ling Y, Gao Y, Gu HY et al (2007) Gambogic acid inhibits angiogenesis through suppressing vascular endothelial growth factor-induced tyrosine phosphorylation of Kdr/Flk-1. Cancer Lett 258:80–89. doi:10.1016/j.canlet.2007.08.015 PubMedCrossRef

Michael D, Oren M (2003) The P53-Mdm2 module and the ubiquitin system. Semin Cancer Biol 13:49–58. doi:10.1016/S1044-579X(02)00099-8 PubMedCrossRef

Pandey MK, Sung B, Ahn KS, Kunnumakkara AB, Chaturvedi MM, Aggarwal BB (2007) Gambogic acid, a novel ligand for transferrin receptor, potentiates Tnf-induced apoptosis through modulation of the nuclear factor-kappab signaling pathway. Blood 110:3517–3525. doi:10.1182/blood-2007-03-079616 PubMedCrossRef

Qin Y, Meng L, Hu C, Duan W, Zuo Z, Lin L et al (2007) Gambogic acid inhibits the catalytic activity of human topoisomerase iialpha by binding to its atpase domain. Mol Cancer Ther 6:2429–2440. doi:10.1158/1535-7163.MCT-07-0147 PubMedCrossRef

Roger L, Gadea G, Roux P (2006) Control of cell migration: a tumour suppressor function for P53? Biol Cell 98:141–152. doi:10.1042/BC20050058 PubMedCrossRef

Smith DJ, Ng H, Kluck RM, Nagley P (2008) The mitochondrial gateway to cell death. IUBMB Life 60:383–389. doi:10.1002/iub.44 PubMedCrossRef

Tomita Y, Marchenko N, Erster S, Nemajerova A, Dehner A, Klein C et al (2006) Wt P53, but not tumor-derived mutants, bind to Bcl2 via the DNA binding domain and induce mitochondrial permeabilization. J Biol Chem 281:8600–8606. doi:10.1074/jbc.M507611200 PubMedCrossRef

Wang X, Chen Y, Han QB, Chan CY, Wang H, Liu Z et al (2009) Proteomic identification of molecular targets of gambogic acid: role of stathmin in hepatocellular carcinoma. Proteomics 9:242–253. doi:10.1002/pmic.200800155 PubMedCrossRef

Wu ZQ, Guo QL, You QD, Zhao L, Gu HY (2004) Gambogic acid inhibits proliferation of human lung carcinoma Spc-A1 cells in vivo and in vitro and represses telomerase activity and telomerase reverse transcriptase Mrna expression in the cells. Biol Pharm Bull 27:1769–1774. doi:10.1248/bpb.27.1769 PubMedCrossRef

Xia M, Land H (2007) Tumor suppressor P53 restricts ras stimulation of rhoa and cancer cell motility. Nat Struct Mol Biol 14:215–223. doi:10.1038/nsmb1208 PubMedCrossRef

Yang QZ, Jia SJ, Li DH (1994) The neoteric study of chinese traditional drug, gamboge. Chin J Clin Oncol 21:464–465

Yang Y, Yang L, You QD, Nie FF, Gu HY, Zhao L et al (2007) Differential apoptotic induction of gambogic acid, a novel anticancer natural product, on hepatoma cells and normal hepatocytes. Cancer Lett 256:259–266. doi:10.1016/j.canlet.2007.06.014 PubMedCrossRef

Yu J, Guo QL, You QD, Zhao L, Gu HY, Yang Y et al (2007) Gambogic acid-induced G2/M phase cell-cycle arrest via disturbing Cdk7-mediated phosphorylation of Cdc2/P34 in human gastric carcinoma Bgc-823 cells. Carcinogenesis 28:632–638. doi:10.1093/carcin/bgl168 PubMedCrossRef

Zhai D, Jin C, Shiau CW, Kitada S, Satterthwait AC, Reed JC (2008) Gambogic acid is an antagonist of antiapoptotic Bcl-2 family proteins. Mol Cancer Ther 7:1639–1646. doi:10.1158/1535-7163.MCT-07-2373 PubMedCrossRef

Zhang HZ, Kasibhatla S, Wang Y, Herich J, Guastella J, Tseng B et al (2004) Discovery, characterization and Sar of gambogic acid as a potent apoptosis inducer by a Hts assay. Bioorg Med Chem 12:309–317. doi:10.1016/j.bmc.2003.11.013 PubMedCrossRef

Zhao L, Guo QL, You QD, Wu ZQ, Gu HY (2004) Gambogic acid induces apoptosis and regulates expressions of Bax and Bcl-2 protein in human gastric carcinoma Mgc-803 cells. Biol Pharm Bull 27:998–1003. doi:10.1248/bpb.27.998 PubMedCrossRef

Zhao Q, Yang Y, Yu J, You QD, Zeng S, Gu HY et al (2008) Posttranscriptional regulation of the telomerase Htert by gambogic acid in human gastric carcinoma 823 cells. Cancer Lett 262:223–231. doi:10.1016/j.canlet.2007.12.002 PubMedCrossRef

Titel: Gambogic acid reduced bcl-2 expression via p53 in human breast MCF-7 cancer cells
verfasst von: Hongyan Gu
Shuyun Rao
Jie Zhao
Jia Wang
Rong Mu
Jingjing Rong
Lei Tao
Qi Qi
Qidong You
Qinglong Guo
Publikationsdatum: 01.12.2009
Verlag: Springer-Verlag
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 12/2009
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-009-0624-2

Neu im Fachgebiet Onkologie

25.04.2024 | Nierenkarzinom | Nachrichten

Springer Medizin

Gambogic acid reduced bcl-2 expression via p53 in human breast MCF-7 cancer cells

Abstract

Purpose

Method

Results

Conclusions

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie

Springer Medizin

Abstract

Purpose

Method

Results

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 12/2009

Intraoperative hyperthermic intraperitoneal chemotherapy after cytoreductive surgery in ovarian cancer peritoneal carcinomatosis: systematic review of current results

Adenovirally mediated p53 overexpression diversely influence the cell cycle of HEp-2 and CAL 27 cell lines upon cisplatin and methotrexate treatment

Activating mutations within the EGFR kinase domain: a molecular predictor of disease-free survival in resected pulmonary adenocarcinoma

Glioblastoma cells express functional cell membrane receptors activated by daily used medical drugs

Elimination of high-risk human papillomavirus type HPV16 infection by ‘Praneem’ polyherbal tablet in women with early cervical intraepithelial lesions

Survival in non-Hodgkin’s lymphoma by histology and family history

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie