Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

Platycodin D Induces Apoptosis, and Inhibits Adhesion, Migration and Invasion in HepG2 Hepatocellular Carcinoma Cells

  • Li, Ting (State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau) ;
  • Xu, Wen-Shan (State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau) ;
  • Wu, Guo-Sheng (State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau) ;
  • Chen, Xiu-Ping (State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau) ;
  • Wang, Yi-Tao (State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau) ;
  • Lu, Jin-Jian (State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau)
  • Published : 2014.02.28
Download PDF
⟨ Previous Next ⟩

Abstract

Background: Platycodin D (PD), a triterpenoid saponin isolated from the Chinese medicinal herb Platycodonis radix, possesses anti-cancer effects in several cancer cell lines. The aim of this study was to evaluate its anticancer activities in hepatocellular carcinoma cells. Materials and Methods: MTT and colony formation assays were performed to evaluate cell proliferation, along with flow cytometry and Western blotting for apoptosis. Cell adhesion was tested by observing cellular morphology under a microscope, while the transwell assay was employed to investigate the cell migration and invasion. Results: PD concentration-dependently inhibited cell proliferation in both HepG2 and Hep3B cells, and significantly suppressed colony formation and induced apoptosis in HepG2 cells. The protein levels of cleaved poly ADP-ribose polymerase (PARP) and Bax were up-regulated while that of survivin was down-regulated after treatment with PD. Moreover, PD not only obviously suppressed the adhesion of HepG2 cells to Matrigel, but also remarkably depressed their migration and invasion induced by 12-O-tetradecanoylphorbol 13-acetate (TPA). Conclusions: PD presents anti-cancer potential in hepatocellular carcinoma cells via inducing apoptosis, and inhibiting cell adhesion, migration and invasion, indicating promising features as a lead compound for anti-cancer agent development.

Keywords

References

  1. Ahn KS, Noh EJ, Zhao HL, et al (2005). Inhibition of inducible nitric oxide synthase and cyclooxygenase II by Platycodon grandiflorum saponins via suppression of nuclear factorkappaB activation in RAW 264.7 cells. Life Sci, 76, 2315-28. https://doi.org/10.1016/j.lfs.2004.10.042
  2. Boulares AH, Yakovlev AG, Ivanova V, et al (1999). Role of poly(ADP-ribose) polymerase (PARP) cleavage in apoptosis. Caspase 3-resistant PARP mutant increases rates of apoptosis in transfected cells. J Biol Chem, 274, 22932-40. https://doi.org/10.1074/jbc.274.33.22932
  3. Brady HJ, Gil-Gomez G (1998). Bax. The pro-apoptotic Bcl-2 family member, Bax. Int J Biochem Cell Biol, 30, 647-50. https://doi.org/10.1016/S1357-2725(98)00006-5
  4. Chen WQ, Zheng RS, Zhang SW (2013). Liver cancer incidence and mortality in China, 2009. Chin J Cancer, 32, 162-9. https://doi.org/10.5732/cjc.013.10027
  5. Chen X, Bao J, Guo J, et al (2012). Biological activities and potential molecular targets of cucurbitacins: a focus on cancer. Anticancer Drugs, 23, 777-87. https://doi.org/10.1097/CAD.0b013e3283541384
  6. Cheng AL, Kang YK, Chen Z, et al (2009). Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, doubleblind, placebo-controlled trial. Lancet Oncol, 10, 25-34. https://doi.org/10.1016/S1470-2045(08)70285-7
  7. Choi SS, Han EJ, Lee TH, et al (2002). Antinociceptive mechanisms of platycodin D administered intracerebroventricularly in the mouse. Planta Medica, 68, 794-8. https://doi.org/10.1055/s-2002-34396
  8. Choi YH, Yoo DS, Cha MR, et al (2010). Antiproliferative effects of saponins from the roots of Platycodon grandiflorum on cultured human tumor cells. J Nat Prod, 73, 1863-7. https://doi.org/10.1021/np100496p
  9. Chun J, Joo EJ, Kang M, et al (2012). Platycodin D induces anoikis and caspase-mediated apoptosis via p38 MAPK in AGS human gastric cancer cells. J Cell Biochem. ????
  10. El-Serag HB (2002). Hepatocellular carcinoma: an epidemiologic view. J Clin Gastroenterol, 35, S72-8. https://doi.org/10.1097/00004836-200211002-00002
  11. Genda T, Sakamoto M, Ichida T, et al (1999). Cell motility mediated by rho and Rho-associated protein kinase plays a critical role in intrahepatic metastasis of human hepatocellular carcinoma. Hepatology, 30, 1027-36. https://doi.org/10.1002/hep.510300420
  12. Han LK, Zheng YN, Xu BJ, et al (2002). Saponins from platycodi radix ameliorate high fat diet-induced obesity in mice. Journal of Nutrition, 132, 2241-5. https://doi.org/10.1093/jn/132.8.2241
  13. Huang M, Lu JJ, Huang MQ, et al (2012). Terpenoids: natural products for cancer therapy. Expert Opin Investig Drugs, 21, 1801-18. https://doi.org/10.1517/13543784.2012.727395
  14. Hughes CS, Postovit LM, Lajoie GA (2010). Matrigel: a complex protein mixture required for optimal growth of cell culture. Proteomics, 10, 1886-90. https://doi.org/10.1002/pmic.200900758
  15. Kim MO, Moon DO, Choi YH, et al (2008a). Platycodin D induces mitotic arrest in vitro, leading to endoreduplication, inhibition of proliferation and apoptosis in leukemia cells. Int J Cancer, 122, 2674-81. https://doi.org/10.1002/ijc.23442
  16. Kim MO, Moon DO, Choi YH, et al (2008b). Platycodin D induces apoptosis and decreases telomerase activity in human leukemia cells. Cancer Lett, 261, 98-107. https://doi.org/10.1016/j.canlet.2007.11.010
  17. Kim YP, Lee EB, Kim SY, et al (2001). Inhibition of prostaglandin E2 production by platycodin D isolated from the root of Platycodon grandiflorum. Planta Med, 67, 362-4. https://doi.org/10.1055/s-2001-14317
  18. Kim YS, Kim JS, Choi SU, et al (2005). Isolation of a new saponin and cytotoxic effect of saponins from the root of Platycodon grandiflorum on human tumor cell lines. Planta Med, 71, 566-8. https://doi.org/10.1055/s-2005-864161
  19. Lee H, Kang R, Kim YS, et al (2010). Platycodin D inhibits adipogenesis of 3T3-L1 cells by modulating Kruppel-like factor 2 and peroxisome proliferator-activated receptor gamma. Phytother Res, 24 Suppl 2, S161-7.
  20. Llovet JM, Ricci S, Mazzaferro V, et al (2008). Sorafenib in advanced hepatocellular carcinoma. N Engl J Med, 359, 378-90. https://doi.org/10.1056/NEJMoa0708857
  21. Lu JJ, Bao JL, Chen XP, et al (2012a). Alkaloids isolated from natural herbs as the anticancer agents. Evid Based Complement Alternat Med, 2012, 485042.
  22. Lu JJ, Bao JL, Wu GS, et al (2013). Quinones derived from plant secondary metabolites as anti-cancer agents. Anticancer Agents Med Chem, 13, 456-63.
  23. Lu JJ, Dang YY, Huang M, et al (2012b). Anti-cancer properties of terpenoids isolated from Rhizoma curcumae--a review. J Ethnopharmacol, 143, 406-11. https://doi.org/10.1016/j.jep.2012.07.009
  24. Pharmacopoeia Commission of the Ministry of Health of the P.R.China (2010). Pharmacopoeia of the People's Republic of China. China Medical Science Press.
  25. Shimao Y, Nabeshima K, Inoue T, et al (1999). TPA-enhanced motility and invasion in a highly metastatic variant (L-10) of human rectal adenocarcinoma cell line RCM-1: selective role of PKC-alpha and its inhibition by a combination of PDBuinduced PKC downregulation and antisense oligonucleotides treatment. Clin Exp Metastasis, 17, 351-60.
  26. Shin DY, Kim GY, Li W, et al (2009). Implication of intracellular ROS formation, caspase-3 activation and Egr-1 induction in platycodon D-induced apoptosis of U937 human leukemia cells. Biomed Pharmacother, 63, 86-94. https://doi.org/10.1016/j.biopha.2008.08.001
  27. Wu JT, Yang GW, Zhu WX, et al (2012). Anti-atherosclerotic activity of platycodin d derived from roots of Platycodon grandiflorum in human endothelial cells. Biological Pharmaceutical Bulletin, 35, 1216-21. https://doi.org/10.1248/bpb.b-y110129
  28. Xie Y, Deng W, Sun H, et al (2008). Platycodin D2 is a potential less hemolytic saponin adjuvant eliciting Th1 and Th2 immune responses. International Immunopharmacology, 8, 1143-50. https://doi.org/10.1016/j.intimp.2008.04.006
  29. Yamamoto H, Ngan CY, Monden M (2008). Cancer cells survive with survivin. Cancer Sci, 99, 1709-14. https://doi.org/10.1111/j.1349-7006.2008.00870.x
  30. Ye QH, Qin LX, Forgues M, et al (2003). Predicting hepatitis B virus-positive metastatic hepatocellular carcinomas using gene expression profiling and supervised machine learning. Nat Med, 9, 416-23. https://doi.org/10.1038/nm843
  31. Yu JS, Kim AK (2010). Platycodin D induces apoptosis in MCF-7 human breast cancer cells. J Med Food, 13, 298-305. https://doi.org/10.1089/jmf.2009.1226

Cited by

  1. Clinical Significance of Joint Detection of Serum VEGF, SIL-2R and HGF in Patients with Primary Hepatocellular Carcinoma before and after Percutaneous Microwave Coagulation Therapy vol.15, pp.11, 2014, https://doi.org/10.7314/APJCP.2014.15.11.4545
  2. Saponins from Rubus parvifolius L. Induce Apoptosis in Human Chronic Myeloid Leukemia Cells through AMPK Activation and STAT3 Inhibition vol.15, pp.13, 2014, https://doi.org/10.7314/APJCP.2014.15.13.5455
  3. Fungal Taxol Extracted from Cladosporium oxysporum Induces Apoptosis in T47D Human Breast Cancer Cell Line vol.15, pp.16, 2014, https://doi.org/10.7314/APJCP.2014.15.16.6627
  4. Preclinical Trials for Prevention of Tumor Progression of Hepatocellular Carcinoma by LZ-8 Targeting c-Met Dependent and Independent Pathways vol.10, pp.1, 2015, https://doi.org/10.1371/journal.pone.0114495
  5. Metastatic Inhibitory and Radical Scavenging Efficacies of Saponins Extracted from the Brittle Star (Ophiocoma erinaceus) vol.16, pp.11, 2015, https://doi.org/10.7314/APJCP.2015.16.11.4751
  6. Steroidal Saponins from Paris polyphylla Induce Apoptotic Cell Death and Autophagy in A549 Human Lung Cancer Cells vol.16, pp.3, 2015, https://doi.org/10.7314/APJCP.2015.16.3.1169
  7. Killing cancer with platycodin D through multiple mechanisms vol.20, pp.3, 2015, https://doi.org/10.1111/jcmm.12749
  8. Activation of Caspase-9/3 and Inhibition of Epithelial Mesenchymal Transition are Critically Involved in Antitumor Effect of Phytol in Hepatocellular Carcinoma Cells vol.29, pp.7, 2015, https://doi.org/10.1002/ptr.5342
  9. Platycodin D induces apoptosis and triggers ERK- and JNK-mediated autophagy in human hepatocellular carcinoma BEL-7402 cells vol.36, pp.12, 2015, https://doi.org/10.1038/aps.2015.99
  10. The inhibition of Platycodin D on Mycoplasma pneumoniae proliferation and its effect on promoting cell growth after anti-Mycoplasma pneumoniae treatment vol.4, pp.2235-2988, 2015, https://doi.org/10.3389/fcimb.2014.00192
  11. vol.40, pp.3, 2015, https://doi.org/10.1111/jfbc.12217
  12. Saponins from Chinese Medicines as Anticancer Agents vol.21, pp.10, 2016, https://doi.org/10.3390/molecules21101326
  13. Platycodin D, a metabolite of Platycodin grandiflorum, inhibits highly metastatic MDA-MB-231 breast cancer growth in vitro and in vivo by targeting the MDM2 oncogene vol.36, pp.3, 2016, https://doi.org/10.3892/or.2016.4935
  14. Platycodin D exerts anti-tumor efficacy in H22 tumor-bearing mice via improving immune function and inducing apoptosis vol.41, pp.3, 2016, https://doi.org/10.2131/jts.41.417
  15. Platycodin D inhibits B16F10 melanoma metastasis via antiangiogenic activity vol.6, pp.13, 2016, https://doi.org/10.1039/C5RA23725D
  16. Candidate Genes Involved in the Biosynthesis of Triterpenoid Saponins in Platycodon grandiflorum Identified by Transcriptome Analysis vol.7, pp.1664-462X, 2016, https://doi.org/10.3389/fpls.2016.00673
  17. Differential Tissue-specific and Pathway-specific Anti-obesity Effects of Green Tea and Taeumjowitang, a Traditional Korean Medicine, in Mice vol.22, pp.3, 2017, https://doi.org/10.15430/JCP.2017.22.3.147
  18. , suppresses the growth and invasion of human oral squamous cell carcinoma cells via the NF-κB pathway vol.31, pp.9, 2017, https://doi.org/10.1002/jbt.21934
  19. Preventive and Therapeutic Effects of Chinese Herbal Compounds against Hepatocellular Carcinoma vol.21, pp.2, 2016, https://doi.org/10.3390/molecules21020142
  20. A Systems-Level Analysis of Mechanisms of Platycodon grandiflorum Based on A Network Pharmacological Approach vol.23, pp.11, 2018, https://doi.org/10.3390/molecules23112841
  21. Role of MicroRNAs Induced by Chinese Herbal Medicines Against Hepatocellular Carcinoma: A Brief Review pp.1552-695X, 2018, https://doi.org/10.1177/1534735418805564
  22. Total Saponins of Rubus Parvifolius L. Exhibited Anti-Leukemia Effect in vivo through STAT3 and eIF4E Signaling Pathways pp.1993-0402, 2018, https://doi.org/10.1007/s11655-018-2563-8