DOI QR코드

DOI QR Code

Gartanin enhances TRAIL-mediated liver cancer cell death through DR5 upregulation and autophagy activation

  • Dong-Oh Moon (Department of Biology Education, Daegu University)
  • Received : 2023.01.15
  • Accepted : 2023.01.31
  • Published : 2023.12.31

Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has no effect on normal cells, but selectively can induce apoptosis in tumor cells. Gartanin, a xanthone compound in mangosteen, has been shown to inhibit cancer cell growth by arresting the cell cycle and inducing autophage. In this study, we revealed that gartanin can sensitize TRAIL-induced human liver cancer cell death. We also found that gartanin enhances DR5 expression, a death receptor for TRAIL. This effect appears to be related to CHOP activation associated with the response of endoplasmic reticulum stress. Gartanin treatment also inhibited p62 protein expression and cleaved LC3 to activate autophagy flux, which is related with TRAIL-induced cell death. Pretreatment with autophagy flux inhibitor, LY294002, inhibited gartanin-induced DR5 expression. In summary, our results reveal that the combined treatment of gartanin and TRAIL can be a valuable tool for cancer treatment.

Keywords

Acknowledgement

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government(MSIT) (No. NRF-2020R1F1A1072032).

References

  1. Leong S, Cohen RB, Gustafson DL, Langer CJ, Camidge DR, Padavic K, Gore L, Smith M, Chow LQ, von Mehren M, O'Bryant C, Hariharan S, Diab S, Fox NL, Miceli R, Eckhardt SG (2009) Mapatumumab, an antibody targeting TRAIL-R1, in combination with paclitaxel and carboplatin in patients with advanced solid malignancies: results of a phase I and pharmacokinetic study. J Clin Oncol 27: 4413-4421. doi:10.1200/JCO.2008.21.7422
  2. Chen X, Thakkar H, Tyan F, Gim S, Robinson H, Lee C, Pandey SK, Nwokorie C, Onwudiwe N, Srivastava RK (2001) Constitutively active Akt is an important regulator of TRAIL sensitivity in prostate cancer. Oncogene 20: 6073-6083. doi: 10.1038/sj.onc.1204736
  3. Walczak H, Miller RE, Ariail K, Gliniak B, Griffith TS, Kubin M, Chin W, Jones J, Woodward A, Le T, Smith C, Smolak P, Goodwin RG, Rauch CT, Schuh JC, Lynch DH (1999) Tumoricidal activity of tumor necrosis factor-related apoptosis-inducing ligand in vivo. Nature Medicine 5: 157-163. doi: 10.1038/5517
  4. Kischkel FC, Lawrence DA, Chuntharapai A, Schow P, Kim KJ, Ashkenazi A (2000) Apo2L/TRAIL-dependent recruitment of endogenous FADD and caspase-8 to death receptors 4 and 5. Immunity 12: 611-620. doi: 10.1016/S1074-7613(00)80212-5
  5. Ashkenazi A, Dixit VM (1998) Death receptors: signaling and modulation. Science 281: 1305-1308. doi: 10.1126/science.281.5381.13
  6. Yamanaka T, Shiraki K, Sugimoto K, Ito T, Fujikawa K, Ito M, Takase K, Moriyama M, Nakano T, Suzuki A (2000) Chemotherapeutic agents augment TRAIL-induced apoptosis in human hepatocellular carcinoma cell lines. Hepatology 32(3): 482-490. doi: 10.1053/jhep.2000.16266
  7. Pedraza-Chaverri J, Cardenas-Rodriguez N, Orozco-Ibarra M (2008) Medicinal properties of mangosteen (Garcinia mangostana). Food Chem Toxicol 46: 3227-3239. doi: 10.1016/j.fct.2008.07.024
  8. Suksamrarn S, Komutiban O, Ratananukul P, Chimnoi N, Lartpornmatulee N, Suksamrarn (2006) Cytotoxic prenylated xanthones from the young fruit of Garcinia mangostana. Chem Pharm Bull 54: 301-305. doi:10.1248/cpb.54.301
  9. Jung HA, Su BN, Keller WJ, Mehta RG, Kinghorn AD (2006) Antioxidant xanthones from the pericarp of Garcinia mangostana (Mangosteen). J Agric Food Chem 54: 2077-2082. doi: 10.1021/jf052649z
  10. Luo M, Liu Q, He M, Yu Z, Pi R, Li M, Yang X, Wang S, Liu A (2017) Gartanin induces cell cycle arrest and autophagy and suppresses migration involving PI3K/Akt/mTOR and MAPK signalling pathway in human glioma cells. J Cell Mol Med 21: 46-57. doi: 10.1111/jcmm.12937
  11. Pham V, Rendon R, Le VX, Tippin M, Fu DJ, Le TH, Miller M, Agredano E, Cedano J, Zi X (2020) Gartanin is a novel NEDDylation inhibitor for induction of Skp2 degradation, FBXW2 expression, and autophagy. Mol Carcinog 259(2): 193-201. doi: 10.1002/mc.23140
  12. Kim BR, Park SH, Jeong YA, Na YJ, Kim JL, Jo MJ, Jeong S, Yun HK, Oh SC, Lee D-H (2009) RUNX3 enhances TRAIL-induced apoptosis by upregulating DR5 in colorectal cancer. Oncogene 38: 3903-3918. doi:10.1038/s41388-019-0693-x
  13. van Geelen CM, Pennarun B, Le PT, de Vries EG, de Jong S (2011) Modulation of TRAIL resistance in colon carcinoma cells: different contributions of DR4 and DR5. BMC Cancer 27: 11-39. doi: 10.1186/1471-2407-11-39
  14. Yamaguchi H, Wang HG (2004) CHOP is involved in endoplasmic reticulum stress-induced apoptosis by enhancing DR5 expression in human carcinoma cells. J Biol Chem 279: 45495-45502. doi: 10.1074/jbc.M406933200
  15. Yoshida T, Shiraishi T, Nakata S, Horinaka M, Wakada M, Mizutani Y, Miki T, Sakai T (2005) Proteasome inhibitor MG132 induces death receptor 5 through CCAAT/enhancer-binding protein homologous protein. Cancer Research 65: 5662-5667. doi: 10.1158/0008-5472.CAN-05-0693
  16. Okada T, Yoshida H, Akazawa R, Negishi M, Mori K (2002) Distinct roles of activating transcription factor 6 (ATF6) and double-stranded RNA-activated protein kinase-like endoplasmic reticulum kinase (PERK) in transcription during the mammalian unfolded protein response. Biochem J 366: 585-594. doi: 10.1042/bj20020391
  17. Szegezdi E, Logue SE, Gorman AM, Samali A (2006) Mediators of endoplasmic reticulum stress-induced apoptosis. EMBO Rep 7: 880-885. doi: 10.1038/sj.embor.7400779
  18. Malhotra JD, Kaufman RJ (2007) The endoplasmic reticulum and the unfolded protein response. Semin Cell Dev Biol 18: 716-731. doi:10.1016/j.semcdb.2007.09.003
  19. Gupta SC, Hevia D, Patchva S, Park B, Koh W, Aggarwal BB (2012) Upsides and downsides of reactive oxygen species for cancer: the roles of reactive oxygen species in tumorigenesis, prevention, and therapy. Antioxidants and Redox Signaling 16(11): 1295-1322. doi: 10.1089/ars.2011.4414
  20. Sciarretta S, Zhai P, Shao D, Zablocki D, Nagarajan N, S. Terada L, Volpe M, Sadoshima J (2013) Activation of NADPH oxidase 4 in the endoplasmic reticulum promotes cardiomyocyte autophagy and survival during energy stress through the protein kinase RNA-activated-like endoplasmic reticulum kinase/eukaryotic initiation factor 2α/activating transcription factor 4 pathway. Circulation Research 113: 1253-1264. doi: 10.1161/CIRCRESAHA.113.301787
  21. Kroemer G, Marino G, Levine B (2010) Autophagy and the integrated stress response. Mol cell 40: 280-293. doi: 10.1016/j.molcel.2010.09.023
  22. Meng T, Lin S, Zhuang H, Huang H, He Z, Hu Y, Gong Q, Feng D (2019) Recent progress in the role of autophagy in neurological diseases. Cell Stress 29: 141-161. doi: 10.15698/cst2019.05.186
  23. Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T, Noda T, Kominami E, Ohsumi Y, Yoshimori T (2000) LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. The EMBO Journal 19: 5720-5728. doi: 10.1093/emboj/19.21.5720
  24. Seibenhener ML, Babu JR, Geetha T, Wong HC, Krishna NR, Wooten MW (2004) Sequestosome 1/p62 is a polyubiquitin chain binding protein involved in ubiquitin proteasome degradation. Mol Cell Biol 24(18):8055-8068. doi: 10.1128/MCB.24.18.8055-8068.2004
  25. Mora R, Abschuetz A, Kees T, Dokic I, Joschko N, Kleber S, Geibig R, Mosconi E, Zentgraf H, Martin-Villalba A, Regnier-Vigouroux A (2009) TNF-alpha- and TRAIL-resistant glioma cells undergo autophagy-dependent cell death induced by activated microglia. Glia 57: 561-581. doi: 10.1002/glia.20785
  26. Herrero-Martin G, Hoyer-Hansen M, Garcia-Garcia C, Fumarola C, Farkas T, Lopez-Rivas A, Jaattela M (2009) TAK1 activates AMPK-dependent cytoprotective autophagy in TRAIL-treated epithelial cells. The EMBO journal 28: 677-685. doi: 10.1038/emboj.2009.8
  27. Nazim UM, Moon JH, Lee JH, Lee YJ, Seol JW, Eo SK, Lee JH, Park SY (2016) Activation of autophagy flux by metformin downregulates cellular FLICE-like inhibitory protein and enhances TRAIL-induced apoptosis. Oncotarget 26: 23468-23481. doi: 10.18632/oncotarget.8048
  28. Chen L, Meng Y, Sun Q, Zhang Z, Guo X, Sheng X, Tai G, Cheng H, Zhou Y (2016) Ginsenoside compound K sensitizes human colon cancer cells to TRAIL-induced apoptosis via autophagy-dependent and - independent DR5 upregulation. Cell Death Dis 11: 1-222. doi: 10.1038/cddis.2016.234
  29. Prasad S, Kim JH, Gupta SC, Aggarwal BB (2014) Targeting death receptors for TRAIL by agents designed by Mother Nature. Trends Pharmacol Sci 35: 520-536. doi: 10.1016/j.tips.2014.07.004
  30. Sung B, Park B, Yadav VR, Aggarwal BB (2010) Celastrol, a triterpene, enhances TRAIL-induced apoptosis through the down-regulation of cell survival proteins and up-regulation of death receptors. J Biol Chem 285: 16920. doi: 10.1074/jbc.M109.090209
  31. Hayashi T, Saito A, Okuno S, Ferrand-Drake M, Dodd RL, Nishi T, Maier CM, Kinouchi H, Chan PH (2003) Oxidative damage to the endoplasmic reticulum is implicated in ischemic neuronal cell death. J Cereb Blood Flow Metab 23: 1117-1128