TRAIL Pathway is Associated with Inhibition of Colon Cancer by Protopanaxadiol

Overview

Journal J Pharmacol Sci

Specialty Pharmacology

Date 2015 Feb 24

PMID 25704023

Citations 13

Authors

Zhiyu Zhang

Zejuan Li

Xiaohui Wu

Chun-Feng Zhang

Tyler Calway

Tong-Chuan He

Wei Du

Jianjun Chen

Chong-Zhi Wang

Chun-Su Yuan

Affiliations

Soon will be listed here.

Abstract

Among important components of American ginseng, protopanaxadiol (PPD) showed more active anticancer potential than other triterpenoid saponins. In this study, we determined the in vivo effects of PPD in a mouse cancer model first. Then, using human colorectal cancer cell lines, we observed significant cancer cell growth inhibition by promoting G1 cell cycle redistribution and apoptosis. Subsequently, we characterized the downstream genes targeted by PPD in HCT-116 cancer cells. Using Affymetrix high density GeneChips, we obtained the gene expression profile of the cells. Microarray data indicated that the expression levels of 76 genes were changed over two-fold after PPD, of which 52 were upregulated while the remaining 24 were downregulated. Ingenuity pathway analysis of top functions affected was carried out. Data suggested that by regulating the interactions between p53 and DR4/DR5, the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) pathway played a key role in the action of PPD, a promising colon cancer inhibitory compound.

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References

He B, Gao J, Luo X, Luo J, Shen J, Wang L . Ginsenoside Rg3 inhibits colorectal tumor growth through the down-regulation of Wnt/ß-catenin signaling. Int J Oncol. 2010; 38(2):437-45. DOI: 10.3892/ijo.2010.858. View

Yamaguchi H, Wang H . CHOP is involved in endoplasmic reticulum stress-induced apoptosis by enhancing DR5 expression in human carcinoma cells. J Biol Chem. 2004; 279(44):45495-502. DOI: 10.1074/jbc.M406933200. View

Zhang Y, Zhang R, Xu H, Yu X, Qu S, Sui D . 20(S)-protopanaxadiol triggers mitochondrial-mediated apoptosis in human lung adenocarcinoma A549 cells via inhibiting the PI3K/Akt signaling pathway. Am J Chin Med. 2013; 41(5):1137-52. DOI: 10.1142/S0192415X13500778. View

Irizarry R, Bolstad B, Collin F, Cope L, Hobbs B, Speed T . Summaries of Affymetrix GeneChip probe level data. Nucleic Acids Res. 2003; 31(4):e15. PMC: 150247. DOI: 10.1093/nar/gng015. View

Newman D, Cragg G . Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007; 70(3):461-77. DOI: 10.1021/np068054v. View

Wang S, Li W, Xue Z, Lu Y, Narsinh K, Fan W . Molecular imaging of p53 signal pathway in lung cancer cell cycle arrest induced by cisplatin. Mol Carcinog. 2012; 52(11):900-7. DOI: 10.1002/mc.21930. View

Du G, Dai Q, Williams S, Wang C, Yuan C . Synthesis of protopanaxadiol derivatives and evaluation of their anticancer activities. Anticancer Drugs. 2010; 22(1):35-45. PMC: 2992804. DOI: 10.1097/CAD.0b013e32833fde29. View

Jemal A, Ward E, Thun M . Declining death rates reflect progress against cancer. PLoS One. 2010; 5(3):e9584. PMC: 2834749. DOI: 10.1371/journal.pone.0009584. View

Wolff N, McKay R, Brugarolas J . REDD1/DDIT4-independent mTORC1 inhibition and apoptosis by glucocorticoids in thymocytes. Mol Cancer Res. 2014; 12(6):867-77. PMC: 4260655. DOI: 10.1158/1541-7786.MCR-13-0625. View

10.

Gannon H, Jones S . Using Mouse Models to Explore MDM-p53 Signaling in Development, Cell Growth, and Tumorigenesis. Genes Cancer. 2012; 3(3-4):209-18. PMC: 3494369. DOI: 10.1177/1947601912455324. View

11.

Luo X, Chen J, Song W, Tang N, Luo J, Deng Z . Osteogenic BMPs promote tumor growth of human osteosarcomas that harbor differentiation defects. Lab Invest. 2008; 88(12):1264-77. PMC: 9901484. DOI: 10.1038/labinvest.2008.98. View

12.

Caldon C, Sergio C, Kang J, Muthukaruppan A, Boersma M, Stone A . Cyclin E2 overexpression is associated with endocrine resistance but not insensitivity to CDK2 inhibition in human breast cancer cells. Mol Cancer Ther. 2012; 11(7):1488-99. DOI: 10.1158/1535-7163.MCT-11-0963. View

13.

Lee H, Cha S, Lee M, Cho G, Choi W, Suk K . Role of antiproliferative B cell translocation gene-1 as an apoptotic sensitizer in activation-induced cell death of brain microglia. J Immunol. 2003; 171(11):5802-11. DOI: 10.4049/jimmunol.171.11.5802. View

14.

Gudas J, Payton M, Thukral S, Chen E, Bass M, ROBINSON M . Cyclin E2, a novel G1 cyclin that binds Cdk2 and is aberrantly expressed in human cancers. Mol Cell Biol. 1998; 19(1):612-22. PMC: 83919. DOI: 10.1128/MCB.19.1.612. View

15.

Lee J, Jung K, Morgan M, Kang Y, Lee H, Koo G . Sensitization of TRAIL-induced cell death by 20(S)-ginsenoside Rg3 via CHOP-mediated DR5 upregulation in human hepatocellular carcinoma cells. Mol Cancer Ther. 2012; 12(3):274-85. DOI: 10.1158/1535-7163.MCT-12-0054. View

16.

Shetty S, Gladden J, Henson E, Hu X, Villanueva J, Haney N . Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) up-regulates death receptor 5 (DR5) mediated by NFkappaB activation in epithelial derived cell lines. Apoptosis. 2002; 7(5):413-20. DOI: 10.1023/a:1020031023947. View

17.

Inokuchi M, Uetake H, Shirota Y, Yamada H, Tajima M, Sugihara K . Gene expression of 5-fluorouracil metabolic enzymes in primary colorectal cancer and corresponding liver metastasis. Cancer Chemother Pharmacol. 2004; 53(5):391-6. DOI: 10.1007/s00280-003-0747-0. View

18.

Harper J, Elledge S, Keyomarsi K, Dynlacht B, Tsai L, Zhang P . Inhibition of cyclin-dependent kinases by p21. Mol Biol Cell. 1995; 6(4):387-400. PMC: 301199. DOI: 10.1091/mbc.6.4.387. View

19.

Chen J, McKay R, Parada L . Malignant glioma: lessons from genomics, mouse models, and stem cells. Cell. 2012; 149(1):36-47. PMC: 3719882. DOI: 10.1016/j.cell.2012.03.009. View

20.

Jin Y, Choi J, Shin S, Lee K, Park J, Lee S . Panaxadiol selectively inhibits cyclin A-associated Cdk2 activity by elevating p21WAF1/CIP1 protein levels in mammalian cells. Carcinogenesis. 2003; 24(11):1767-72. DOI: 10.1093/carcin/bgg097. View