DOI QR코드

DOI QR Code

Gambogenic Acid Induction of Apoptosis in a Breast Cancer Cell Line

  • Zhou, Jing (Department of Clinical Medicine, Taizhou People's Hospital) ;
  • Luo, Yan-Hong (Department of Oncology, Jiangsu Cancer Hospital) ;
  • Wang, Ji-Rong (Department of Oncology, Second Affiliated Hospital of Nanjing Medical University) ;
  • Lu, Bin-Bin (Department of Oncology, Second Affiliated Hospital of Nanjing Medical University) ;
  • Wang, Ke-Ming (Department of Oncology, Second Affiliated Hospital of Nanjing Medical University) ;
  • Tian, Ye (Department of Clinical Medicine, Taizhou People's Hospital)
  • Published : 2013.12.31

Abstract

Background: Gambogenic acid is a major active compound of gamboge which exudes from the Garcinia hanburyi tree. Gambogenic acid anti-cancer activity in vitro has been reported in several studies, including an A549 nude mouse model. However, the mechanisms of action remain unclear. Methods: We used nude mouse models to detect the effect of gambogenic acid on breast tumors, analyzing expression of apoptosis-related proteins in vivo by Western blotting. Effects on cell proliferation, apoptosis and apoptosis-related proteins in MDA-MB-231 cells were detected by MTT, flow cytometry and Western blotting. Inhibitors of caspase-3,-8,-9 were also used to detect effects on caspase family members. Results: We found that gambogenic acid suppressed breast tumor growth in vivo, in association with increased expression of Fas and cleaved caspase-3,-8,-9 and bax, as well as decrease in the anti-apoptotic protein bcl-2. Gambogenic acid inhibited cell proliferation and induced cell apoptosis in a concentration-dependent manner. Conclusion: Our observations suggested that Gambogenic acid suppressed breast cancer MDA-MB-231 cell growth by mediating apoptosis through death receptor and mitochondrial pathways in vivo and in vitro.

Keywords

References

  1. American Cancer Society (2011). Learn about Cancer-Breast Cancer. 2011. Available online:http://www.cancer.org/Cancer/BreastCancer/DetailedGuide/ breast-cancer-keystatistics (accessed on 25 May 2011).
  2. Chen HB, Zhou LZ, Mei L,et al (2012). Gambogenic acidinduced time- and dose-dependent growth inhibition and apoptosis involving Akt pathway inactivation in U251 glioblastoma cells. J Nat Med, 66, 62-9. https://doi.org/10.1007/s11418-011-0553-7
  3. Hu C, Huang L, Gest C, et al (2012). Opposite regulation by PI3K/Akt and MAPK/ERK pathways of tissue factor expression, cell-associated procoagulant activity and invasiveness in MDA-MB-231 cells. J Hematol Oncol, 5, 16-35. https://doi.org/10.1186/1756-8722-5-16
  4. Jing GJ, Wang JJ, Zhang SX (2012). ER stress and apoptosis: a new mechanism for retinal cell death. Exp Diabetes Res, 11, 589589.
  5. Kerr JF, Wyllie AH, Currie AR (1972). Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer, 26, 239-57. https://doi.org/10.1038/bjc.1972.33
  6. Kane DJ, Sarafian TA, Anton R, et al (1993). Bcl-2 inhibition of neural death: decreased generation of reactive oxygen species. Science, 262, 1274-7. https://doi.org/10.1126/science.8235659
  7. Kojima Y, Tsurumi H, Goto N, et al (2006). Fas and Fas ligand expression on germinal center typediffuse large B-cell lymphoma is associated with the clinical outcome. Eur J Haematol,76,465-72. https://doi.org/10.1111/j.1600-0609.2006.00631.x
  8. Lu GB, Yang XX, Huang QS (1984). Isolation and structure of neo-gambogic acid from Gamboge (Garcinia hanburryi). Yao Xue Xue Bao 1984, 19, 636-9.
  9. Lei M, Liu JM, Chin J (2003). Cancer Prevent. Treat, 10, 216-9.
  10. Li QL, Cheng H, Zhou A, et al (2010). Gambogenic Acid Inhibits Proliferration of A549 Cells through Apoptosis-Inducing and Cell Cycle Arresting. Biol Pharm Bull, 33, 415-20. https://doi.org/10.1248/bpb.33.415
  11. Lin SX, Chen J, Mazumdar M, et al (2010). Molecular therapy of breast cancer: progress and future directions. Nat Rev Endocrinol, 6, 485-93. https://doi.org/10.1038/nrendo.2010.92
  12. Niu G, Yin S, Xie S, et al (2011). Quercetin induces apoptosis by activating caspase-3 and regulating Bcl-2 and cyclooxygenase-2 pathways in human HL-60 cells. Acta Biochim Biophys Sin (Shanghai), 43, 30-7. https://doi.org/10.1093/abbs/gmq107
  13. Panthong A, Norkaew P, Kanjanapothi D, et al (2008). Antiinflammatory, analgesic and antipyretic activities of the extract of gamboge from Garcinia hanburyi Hook f. J Ethnopharmacol, 111, 335-40.
  14. Perez EA (2009). Impact, mechanisms, and novel chemotherapy strategies for overcoming resistance to anthracyclines and taxanes in metastatic breast cancer. Breast Cancer Research and Treatment, 114, 195-201. https://doi.org/10.1007/s10549-008-0005-6
  15. Park JB, Lee JK, Park EY, Riew KD (2008). Fas/FasL interaction of nucleus pulposus and cancer cells with the activation of caspases. Int Orthop, 32, 835-40. https://doi.org/10.1007/s00264-007-0410-1
  16. Spierings D, Mcstay G, Saleh M, et al (2005). Connected to death: the (unexpurgated) mitochondrial pathway of apoptosis. Science, 310, 66-7. https://doi.org/10.1126/science.1117105
  17. Tan W, Lu JJ, Huang MQ, et al (2011). Anti-cancer natural products isolated from Chinese medical herbs. Chinese Medicine, 6, 27-41. https://doi.org/10.1186/1749-8546-6-27
  18. Tomas NM, Masur K, Piecha JC, Niggemann B, Zanker KS (2012). Akt and phospholipase Cgamma are involved in the regulation of growth and migration of MDA-MB-468 breast cancer and SW480 colon cancer cells when cultured with diabetogenic levels of glucose and insulin. BMC Res Notes, 5, 214-28. https://doi.org/10.1186/1756-0500-5-214
  19. Wang KM, Tang YH, Sun M, et al (2011). The mechanism of neogambogic acid-induced apoptosis in human MCF-7 cells. Acta Biochim Biophys Sin, 43, 698-702. https://doi.org/10.1093/abbs/gmr063
  20. Wang H, Sha W, Liu Z, Chi CW (2011). Effect of chymotrypsin C and related proteins on ancreatic cancer cell migration. Acta Biochim Biophys sin (Shanghai), 43, 362-71. https://doi.org/10.1093/abbs/gmr022
  21. Yan FG, Wang M, Chen H, et al (2011). Gambogenic acid mediated apoptosis through the mitochondrial oxidative stress and inactivation of Akt signaling pathway in human nasopharyngeal carcinoma CNE-1 cells. Eur J Pharmacol, 652, 23-32. https://doi.org/10.1016/j.ejphar.2010.11.018
  22. Yan FG, Wang M, Li JM, et al (2012). Gambogenic acid induced mitochondrial-dependent apoptosis and referred to Phospho-Erk1/2 and Phospho-p38 MAPK in human hepatoma HepG2 cells. Environ Toxicol Pharmacol, 33, 181-90. https://doi.org/10.1016/j.etap.2011.12.006
  23. Zhai DY, Jin CF, Shiau CW, et al (2008). Gambogic acid is an antagonist of antiapoptotic Bcl-2 family Proteins. Mol Cancer Ther, 7, 1639-46. https://doi.org/10.1158/1535-7163.MCT-07-2373
  24. Zhou A, Li QL, Peng DY, et al (2008). Determination of the content of gambogic acid and gambogenic acid in gamboge by HPLC. J Sep Sci, 15, 53-4.

Cited by

  1. Fenofibrate Increases Radiosensitivity in Head and Neck Squamous Cell Carcinoma via Inducing G2/M Arrest and Apoptosis vol.15, pp.16, 2014, https://doi.org/10.7314/APJCP.2014.15.16.6649
  2. 20(S)-Protopanaxadiol Induces Human Breast Cancer MCF-7 Apoptosis through a Caspase-Mediated Pathway vol.15, pp.18, 2014, https://doi.org/10.7314/APJCP.2014.15.18.7919
  3. Rapamycin and PF4 Induce Apoptosis by Upregulating Bax and Down-Regulating Survivin in MNU-Induced Breast Cancer vol.15, pp.9, 2014, https://doi.org/10.7314/APJCP.2014.15.9.3939
  4. A Novel All-trans Retinoid Acid Derivative Induces Apoptosis in MDA-MB-231 Breast Cancer Cells vol.15, pp.24, 2015, https://doi.org/10.7314/APJCP.2014.15.24.10819
  5. Gallic Acid Enhancement of Gold Nanoparticle Anticancer Activity in Cervical Cancer Cells vol.16, pp.1, 2015, https://doi.org/10.7314/APJCP.2015.16.1.169
  6. Gambogenic acid induces proteasomal degradation of CIP2A and sensitizes hepatocellular carcinoma to anticancer agents vol.36, pp.6, 2016, https://doi.org/10.3892/or.2016.5188
  7. Ginsenoside PPD’s Antitumor Effect via Down-Regulation of mTOR Revealed by Super-Resolution Imaging vol.22, pp.3, 2017, https://doi.org/10.3390/molecules22030486
  8. Gambogenic acid alters chemosensitivity of breast cancer cells to Adriamycin vol.15, pp.1, 2015, https://doi.org/10.1186/s12906-015-0710-8