Nelfinavir induces the unfolded protein response in ovarian cancer cells, resulting in ER vacuolization, cell cycle retardation and apoptosis

Cancer Biology and Therapy

Volumn 8, Issue 3, 2009, Pages 226-232

  Brüning, Ansgar ^a   Burger, Petra ^a   Vogel, Marianne ^a   Rahmeh, Martina ^a   Gingelmaier, Andrea ^a   Friese, Klaus ^a   Lenhard, Miriam ^a   Burges, Alexander ^a  

^a LUDWIG MAXIMILIANS UNIVERSITY   (Germany)

Author keywords

Apoptosis; BiP; Cell cycle; ER stress; Nelfinavir; Ovarian cancer; Taxol

Indexed keywords

CARBOPLATIN; CYCLIN A; CYCLIN D3; CYCLIN DEPENDENT KINASE 1; CYCLINE; GLIBENCLAMIDE; GLUCOSE REGULATED PROTEIN 78; HEAT SHOCK PROTEIN 70; INITIATION FACTOR 2ALPHA; NELFINAVIR; PACLITAXEL; CCND3 PROTEIN, HUMAN; HEAT SHOCK PROTEIN; HUMAN IMMUNODEFICIENCY VIRUS PROTEINASE INHIBITOR; INITIATION FACTOR 2; MOLECULAR CHAPERONE GRP78;

APOPTOSIS; ARTICLE; CANCER CELL; CANCER INHIBITION; CANCER RESISTANCE; CELL CYCLE ARREST; CELL CYCLE G0 PHASE; CELL CYCLE G2 PHASE; CELL CYCLE M PHASE; CELL CYCLE S PHASE; CELL DEATH; CELL STRUCTURE; CELL SWELLING; CELL VACUOLE; DOWN REGULATION; DRUG MECHANISM; ENDOPLASMIC RETICULUM STRESS; FEMALE; HUMAN; HUMAN CELL; OVARY CANCER; OVARY CARCINOMA; PROTEIN BINDING; PROTEIN FOLDING; PROTEIN INDUCTION; PROTEIN PHOSPHORYLATION; REACTION TIME; UPREGULATION; BIOSYNTHESIS; CELL CYCLE; CULTURE TECHNIQUE; DRUG EFFECT; ENDOPLASMIC RETICULUM; GENE EXPRESSION REGULATION; GENETICS; METABOLISM; NEOPLASM; OVARY TUMOR; PATHOLOGY; PHOSPHORYLATION; TUMOR CELL LINE;

APOPTOSIS; CELL CULTURE TECHNIQUES; CELL CYCLE; CELL LINE, TUMOR; CYCLIN D3; ENDOPLASMIC RETICULUM; EUKARYOTIC INITIATION FACTOR-2; FEMALE; GENE EXPRESSION REGULATION, NEOPLASTIC; HEAT-SHOCK PROTEINS; HIV PROTEASE INHIBITORS; HUMANS; NELFINAVIR; NEOPLASMS, GLANDULAR AND EPITHELIAL; OVARIAN NEOPLASMS; PHOSPHORYLATION; PROTEIN FOLDING; VACUOLES;

EID: 61449183758     PISSN: 15384047     EISSN: 15558576     Source Type: Journal    
DOI: 10.4161/cbt.8.3.7339     Document Type: Article

References (22)

1. Eltabbakh GH, Awtrey CS. Current treatment for ovarian cancer. Expert Opin Pharmacother 2001; 2:109-24.
2. Lage H, Denkert C. Resistance to chemotherapy in ovarian carcinoma. Recent Results Cancer Res 2007; 176:51-60.
3. Jin Z, El-Deiry WS. Overview of cell death signaling pathways. Cancer Biol Ther 2005; 4:139-63.
4. Fraser M, Leung B, Jahani-Asl A, Yan X, Thompson WE, Tsang BK. Chemoresistance in human ovarian cancer: the role of apoptotic regulators. Reprod Biol Endocrinol 2003; 1:66.
5. Cohen J. HIV drug shows promise as potential cancer treatment. Science 2007; 317:1305.
6. Mastrolorenzo A, Rusconi S, Scozzafava A, Barbaro G, Supuran CT. Inhibitors of HIV-1 protease: current state of the art 10 years after their introduction. From antiretroviral drugs to antifungal, antibacterial and antitumor agents based on aspartic protease inhibitors. Curr Med Chem 2007; 14:2734-48.
7. Sgadari C, Monini P, Barillari G, Ensoli B. Use of HIV protease inhibitors to block Kaposi's sarcoma and tumour growth. Lancet Oncol 2003; 4:537-47.
8. Pyrko P, Kardosh A, Wang W, Xiong W, Schönthal AH, Chen TC. HIV-1 protease inhibitors nelfinavir and atazanavir induce malignant glioma death by triggering endoplasmic reticulum stress. Cancer Res 2007; 67:10920-8.
9. Gills JJ, Lopiccolo J, Dennis PA. Nelfinavir, a new anti-cancer drug with pleiotropic effects and many paths to autophagy. Autophagy 2008; 4:107-9.
10. Fribley A, Wang CY. Proteasome inhibitor induces apoptosis through induction of endoplasmic reticulum stress. Cancer Biol Ther 2006; 5:745-8.
11. Debnath J, Baehrecke EH, Kroemer G. Does Autophagy Contribute To Cell Death? Autophagy 2005; 1:66-75.
12. Wek RC, Jiang HY, Anthony TG. Coping with stress: eIF2 kinases and translational control. Biochem Soc Trans 2006; 34:7-11.
13. Lin JH, Li H, Yasumura D, Cohen HR, Zhang C, Panning B, Shokat KM, Lavail MM, Walter P. IRE1 signaling affects cell fate during the unfolded protein response. Science 2007; 318:944-9.
14. Yorimitsu T, Klionsky DJ. Endoplasmic reticulum stress: a new pathway to induce autophagy. Autophagy 2007; 3:160-2.
15. Bertolotti A, Zhang Y, Hendershot LM, Harding HP, Ron D. Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response. Nat Cell Biol 2000; 2:326-32.
16. Lee AS. The ER chaperone and signaling regulator GRP78/BiP as a monitor of endoplasmic reticulum stress. Methods 2005; 35:373-81.
17. Fels DR, Koumenis C. The PERK/eIF2alpha/ATF4 module of the UPR in hypoxia resistance and tumor growth. Cancer Biol Ther 2006; 5:723-8.
18. Oyadomari S, Mori M. Roles of CHOP/GADD153 in endoplasmic reticulum stress. Cell Death Differ 2004; 11:381-9.
19. Perry CM, Frampton JE, McCormack PL, Siddiqui MA, Cvetkovic RS. Nelfinavir: a review of its use in the management of HIV infection. Drugs 2005; 65:2209-44.
20. Brunner TB, Geiger M, Grabenbauer GG, Lang-Welzenbach M, Mantoni TS, Cavallaro A, Sauer R, Hohenberger W, McKenna WG. Phase I trial of the human immunodeficiency virus protease inhibitor nelfinavir and chemoradiation for locally advanced pancreatic cancer. J Clin Oncol 2008; 26:2699-706.
21. Gills JJ, Lopiccolo J, Tsurutani J, Shoemaker RH, Best CJ, Abu-Asab MS, Borojerdi J, Warfel NA, Gardner ER, Danish M, Hollander MC, Kawabata S, Tsokos M, Figg WD, Steeg PS, Dennis PA. Nelfinavir, A lead HIV protease inhibitor, is a broad-spectrum, anticancer agent that induces endoplasmic reticulum stress, autophagy and apoptosis in vitro and in vivo. Clin Cancer Res 2007; 13:5183-94.
22. Dannenmann C, Shabani N, Friese K, Jeschke U, Mylonas I, Brüning A. The metastasis-associated gene MTA1 is upregulated in advanced ovarian cancer, represses ERbeta and enhances expression of oncogenic cytokine GRO. Cancer Biol Ther 2008; 11:1462-5.