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Article

Gartanin induces autophagy through JNK activation which extenuates caspase-dependent apoptosis

  • Authors:
    • Mun-Ock Kim
    • Hyun-Sun Lee
    • Young-Won Chin
    • Dong-Oh Moon
    • Jong-Seog Ahn
  • View Affiliations / Copyright

    Affiliations: Korea Research Institute of Bioscience and Biotechnology (KRIBB), Ochang, ChungBuk 363‑883, Republic of Korea, Dongguk University-Seoul, Gyeonggi-do, Seoul 410-820, Republic of Korea, Department of Biology Education, Daegu University, Gyungsan, Gyeongbuk 712-714, Republic of Korea
  • Pages: 139-146
    |
    Published online on: May 5, 2015
       https://doi.org/10.3892/or.2015.3948
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Abstract

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Development of novel agents to eradicate liver cancer cells is required for treatment of HCC. Gartanin, a xanthone-type compound isolated from mangosteen, is known to possess potent antioxidant, anti‑inflammatory, antifungal and antineoplastic properties. In the present study, we investigated the cytotoxic effect of gartanin on HCC and explored the cell death mechanism. We showed that gartanin induced both the extrinsic and intrinsic apoptotic pathways, which were interconnected by caspase-8, -9 and -3 activation. We also provided convincing evidence that gartanin induced autophagy in various cancer cells, as demonstrated by acridine orange staining of intracellular acidic vesicles, the degradation of p62, the conversion of LC3-I to LC3-II and GFP-LC3 punctate fluorescence. Additionally, gartanin induced the formation of typical autophagosomes and autolysosomes and enhanced the degradation rate of intracellular granule(s), including mitochondria. Notably, gartanin-mediated apoptotic cell death was further potentiated by pretreatment with autophagy inhibitors (3-methyladenine and bafilomycin A1) or small interfering RNAs against the autophagic genes (Atg5). These findings suggested that gartanin-mediated autophagic response protected against eventual cell death induced by gartanin. Moreover, gartanin treatment led to phosphorylation/activation of JNK and JNK-dependent phosphorylation of Bcl-2. Importantly, JNK inhibitor (SP600125) inhibited autophagy yet promoted gartanin-induced apoptosis, indicating a key requirement of the JNK-Bcl-2 pathway in the activation of autophagy by gartanin. Taken together, our data suggested that the JNK-Bcl-2 pathway was the critical regulator of gartanin-induced protective autophagy and a potential drug target for chemotherapeutic combination.
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1 

Schweichel JU and Merker HJ: The morphology of various types of cell death in prenatal tissues. Teratology. 7:253–266. 1973. View Article : Google Scholar : PubMed/NCBI

2 

Levine B and Yuan J: Autophagy in cell death: An innocent convict? J Clin Invest. 115:2679–2688. 2005. View Article : Google Scholar : PubMed/NCBI

3 

Lieberman AP, Puertollano R, Raben N, Slaugenhaupt S, Walkley SU and Ballabio A: Autophagy in lysosomal storage disorders. Autophagy. 8:719–730. 2012. View Article : Google Scholar : PubMed/NCBI

4 

Klionsky DJ, Abdalla FC, Abeliovich H, Abraham RT, Acevedo-Arozena A, Adeli K, Agholme L, Agnello M, Agostinis P, Aguirre-Ghiso JA, et al: Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy. 8:445–544. 2012. View Article : Google Scholar : PubMed/NCBI

5 

He C and Klionsky DJ: Regulation mechanisms and signaling pathways of autophagy. Annu Rev Genet. 43:67–93. 2009. View Article : Google Scholar : PubMed/NCBI

6 

Sinha S and Levine B: The autophagy effector Beclin 1: A novel BH3-only protein. Oncogene. 27(Suppl 1): S137–S148. 2008. View Article : Google Scholar

7 

Funderburk SF, Wang QJ and Yue Z: The Beclin 1-VPS34 complex - at the crossroads of autophagy and beyond. Trends Cell Biol. 20:355–362. 2010. View Article : Google Scholar : PubMed/NCBI

8 

El-Serag HB and Mason AC: Rising incidence of hepatocellular carcinoma in the United States. N Engl J Med. 340:745–750. 1999. View Article : Google Scholar : PubMed/NCBI

9 

Parkin DM, Pisani P and Ferlay J: Global cancer statistics. CA Cancer J Clin. 49:31–64. 1999. View Article : Google Scholar

10 

Josephs DH and Ross PJ: Sorafenib in hepatocellular carcinoma. Br J Hosp Med. 71:451–456. 2010. View Article : Google Scholar

11 

Suksamrarn S, Komutiban O, Ratananukul P, Chimnoi N, Lartpornmatulee N and Suksamrarn A: Cytotoxic prenylated xanthones from the young fruit of Garcinia mangostana. Chem Pharm Bull. 54:301–305. 2006. View Article : Google Scholar : PubMed/NCBI

12 

Jung HA, Su BN, Keller WJ, Mehta RG and Kinghorn AD: Antioxidant xanthones from the pericarp of Garcinia mangostana (Mangosteen). J Agric Food Chem. 54:2077–2082. 2006. View Article : Google Scholar : PubMed/NCBI

13 

Kikuchi H, Ohtsuki T, Koyano T, Kowithayakorn T, Sakai T and Ishibashi M: Activity of mangosteen xanthones and teleocidin a-2 in death receptor expression enhancement and tumor necrosis factor related apoptosis-inducing ligand assays. J Nat Prod. 73:452–455. 2010. View Article : Google Scholar

14 

Moon DO, Asami Y, Long H, Jang JH, Bae EY, Kim BY, Choi YH, Kang CH, Ahn JS and Kim GY: Verrucarin A sensi-tizes TRAIL-induced apoptosis via the upregulation of DR5 in an eIF2α/CHOP-dependent manner. Toxicol In Vitro. 27:257–263. 2013. View Article : Google Scholar

15 

Colosetti P, Puissant A, Robert G, Luciano F, Jacquel A, Gounon P, Cassuto JP and Auberger P: Autophagy is an important event for megakaryocytic differentiation of the chronic myelogenous leukemia K562 cell line. Autophagy. 5:1092–1098. 2009. View Article : Google Scholar : PubMed/NCBI

16 

Moon DO, Asami Y, Kim MO, Jang JH, Kim BY, Ahn JS, Kim GY and Yun SG: Xestospongin C induces monocytic differentiation of HL60 cells through activation of the ERK pathway. Food Chem Toxicol. 55:505–512. 2013. View Article : Google Scholar : PubMed/NCBI

17 

Mizushima N and Yoshimori T: How to interpret LC3 immunoblotting. Autophagy. 3:542–545. 2007. View Article : Google Scholar : PubMed/NCBI

18 

Li C, Capan E, Zhao Y, Zhao J, Stolz D, Watkins SC, Jin S and Lu B: Autophagy is induced in CD4+ T cells and important for the growth factor-withdrawal cell death. J Immunol. 177:5163–5168. 2006. View Article : Google Scholar : PubMed/NCBI

19 

Jia G, Cheng G, Gangahar DM and Agrawal DK: Insulin-like growth factor-1 and TNF-alpha regulate autophagy through c-jun N-terminal kinase and Akt pathways in human atherosclerotic vascular smooth cells. Immunol Cell Biol. 84:448–454. 2006. View Article : Google Scholar : PubMed/NCBI

20 

Ogata M, Hino S, Saito A, Morikawa K, Kondo S, Kanemoto S, Murakami T, Taniguchi M, Tanii I, Yoshinaga K, et al: Autophagy is activated for cell survival after endoplasmic reticulum stress. Mol Cell Biol. 26:9220–9231. 2006. View Article : Google Scholar : PubMed/NCBI

21 

Chen JL, Lin HH, Kim KJ, Lin A, Forman HJ and Ann DK: Novel roles for protein kinase Cdelta-dependent signaling pathways in acute hypoxic stress-induced autophagy. J Biol Chem. 283:34432–34444. 2008. View Article : Google Scholar : PubMed/NCBI

22 

Geeraert C, Ratier A, Pfisterer SG, Perdiz D, Cantaloube I, Rouault A, Pattingre S, Proikas-Cezanne T, Codogno P and Poüs C: Starvation-induced hyperacetylation of tubulin is required for the stimulation of autophagy by nutrient deprivation. J Biol Chem. 285:24184–24194. 2010. View Article : Google Scholar : PubMed/NCBI

23 

Wei Y, Pattingre S, Sinha S, Bassik M and Levine B: JNK1-mediated phosphorylation of Bcl-2 regulates starvation-induced autophagy. Mol Cell. 30:678–688. 2008. View Article : Google Scholar : PubMed/NCBI

24 

Wagner EF and Nebreda AR: Signal integration by JNK and p38 MAPK pathways in cancer development. Nat Rev Cancer. 9:537–549. 2009. View Article : Google Scholar : PubMed/NCBI

25 

Puissant A, Robert G, Fenouille N, Luciano F, Cassuto JP, Raynaud S and Auberger P: Resveratrol promotes autophagic cell death in chronic myelogenous leukemia cells via JNK-mediated p62/SQSTM1 expression and AMPK activation. Cancer Res. 70:1042–1052. 2010. View Article : Google Scholar : PubMed/NCBI

26 

Li DD, Wang LL, Deng R, Tang J, Shen Y, Guo JF, Wang Y, Xia LP, Feng GK, Liu QQ, et al: The pivotal role of c-Jun NH2-terminal kinase-mediated Beclin 1 expression during anticancer agents-induced autophagy in cancer cells. Oncogene. 28:886–898. 2009. View Article : Google Scholar

27 

Surh YJ: Cancer chemoprevention with dietary phytochemicals. Nat Rev Cancer. 3:768–780. 2003. View Article : Google Scholar : PubMed/NCBI

28 

Maiuri MC, Zalckvar E, Kimchi A and Kroemer G: Self-eating and self-killing: Crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol. 8:741–752. 2007. View Article : Google Scholar : PubMed/NCBI

29 

Shingu T, Fujiwara K, Bögler O, Akiyama Y, Moritake K, Shinojima N, Tamada Y, Yokoyama T and Kondo S: Stage-specific effect of inhibition of autophagy on chemotherapy-induced cytotoxicity. Autophagy. 5:537–539. 2009. View Article : Google Scholar : PubMed/NCBI

30 

Wang QJ, Ding Y, Kohtz DS, Mizushima N, Cristea IM, Rout MP, Chait BT, Zhong Y, Heintz N and Yue Z: Induction of autophagy in axonal dystrophy and degeneration. J Neurosci. 26:8057–8068. 2006. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Kim M, Lee H, Chin Y, Moon D and Ahn J: Gartanin induces autophagy through JNK activation which extenuates caspase-dependent apoptosis. Oncol Rep 34: 139-146, 2015.
APA
Kim, M., Lee, H., Chin, Y., Moon, D., & Ahn, J. (2015). Gartanin induces autophagy through JNK activation which extenuates caspase-dependent apoptosis. Oncology Reports, 34, 139-146. https://doi.org/10.3892/or.2015.3948
MLA
Kim, M., Lee, H., Chin, Y., Moon, D., Ahn, J."Gartanin induces autophagy through JNK activation which extenuates caspase-dependent apoptosis". Oncology Reports 34.1 (2015): 139-146.
Chicago
Kim, M., Lee, H., Chin, Y., Moon, D., Ahn, J."Gartanin induces autophagy through JNK activation which extenuates caspase-dependent apoptosis". Oncology Reports 34, no. 1 (2015): 139-146. https://doi.org/10.3892/or.2015.3948
Copy and paste a formatted citation
x
Spandidos Publications style
Kim M, Lee H, Chin Y, Moon D and Ahn J: Gartanin induces autophagy through JNK activation which extenuates caspase-dependent apoptosis. Oncol Rep 34: 139-146, 2015.
APA
Kim, M., Lee, H., Chin, Y., Moon, D., & Ahn, J. (2015). Gartanin induces autophagy through JNK activation which extenuates caspase-dependent apoptosis. Oncology Reports, 34, 139-146. https://doi.org/10.3892/or.2015.3948
MLA
Kim, M., Lee, H., Chin, Y., Moon, D., Ahn, J."Gartanin induces autophagy through JNK activation which extenuates caspase-dependent apoptosis". Oncology Reports 34.1 (2015): 139-146.
Chicago
Kim, M., Lee, H., Chin, Y., Moon, D., Ahn, J."Gartanin induces autophagy through JNK activation which extenuates caspase-dependent apoptosis". Oncology Reports 34, no. 1 (2015): 139-146. https://doi.org/10.3892/or.2015.3948
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