Ritonavir-mediated induction of apoptosis in pancreatic cancer occurs via the RB/E2F-1 and AKT pathways

Pharmaceuticals

Volumn 7, Issue 1, 2014, Pages 46-57

  Batchu, Ramesh B ^a,b   Gruzdyn, Oksana V ^a,b   Bryant, Christopher S ^c   Qazi, Aamer M ^d   Kumar, Sanjeev ^e   Chamala, Sreedhar ^a,b   Kung, Shu T ^a,b   Sanka, Ramana S ^f   Puttagunta, Udaya S ^g   Weaver, Donald W ^a   Gruber, Scott A ^a,b  

^a WAYNE STATE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b VETERANS AFFAIRS MEDICAL CENTER   (United States)

^c NEA Baptist Clinic   (United States)

^d ONTARIO INSTITUTE FOR CANCER RESEARCH   (Canada)

^e Baptist Medical Group   (United States)

^f Virocan Therapeutics R and D division Yashaswi Hospital   (India)

^g ACHARYA NAGARJUNA UNIVERSITY   (India)

Author keywords

2F 1; AKT; Pancreatic adenocarcinoma; Retinoblastoma; Ritonavir

Indexed keywords

GEMCITABINE; PROTEIN KINASE B; RETINOBLASTOMA PROTEIN; RITONAVIR; TRANSCRIPTION FACTOR E2F1;

ANTIPROLIFERATIVE ACTIVITY; APOPTOSIS; ARTICLE; BINDING SITE; CANCER INHIBITION; CELL INVASION; CELL MOTILITY; CONCENTRATION RESPONSE; CONTROLLED STUDY; DOWN REGULATION; DRUG POTENTIATION; HUMAN; HUMAN CELL; PANCREAS ADENOCARCINOMA; PANCREAS CANCER; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; UPREGULATION;

EID: 84892168247     PISSN: None     EISSN: 14248247     Source Type: Journal    
DOI: 10.3390/ph7010046     Document Type: Article

References (22)

1. Wang, Z.; Li, Y.; Ahmad, A.; Banerjee, S.; Azmi, A.S.; Kong, D.; Sarkar, F.H. Pancreatic cancer: Understanding and overcoming chemoresistance. Nat. Rev. Gastroenterol. Hepatol. 2010, 8, 27-33.
2. Mates, J.M.; Segura, J.A.; Alonso, F.J.; Marquez, J. Anticancer antioxidant regulatory functions of phytochemicals. Curr. Med. Chem. 2011, 18, 2315-2338.
3. Granich, R.; Crowley, S.; Vitoria, M.; Smyth, C.; Kahn, J.G.; Bennett, R.; Lo, Y.-R.; Souteyrand, Y.; Williams, B. Highly active antiretroviral treatment as prevention of HIV transmission: Review of scientific evidence and update. Curr. Opin. HIV AIDS 2010, 5, 298-304.
4. Seaberg, E.C.; Wiley, D.; Martínez-Maza, O.; Chmiel, J.S.; Kingsley, L.; Tang, Y.; Margolick, J.B.; Jacobson, L.P. Cancer incidence in the multicenter aids cohort study before and during the HAART era. Cancer 2010, 116, 5507-5516.
5. Kumar, S.; Bryant, C.S.; Chamala, S.; Qazi, A.; Seward, S.; Pal, J.; Steffes, C.P.; Weaver, D.W.; Morris, R.; Malone, J.M. Ritonavir blocks AKT signaling, activates apoptosis and inhibits migration and invasion in ovarian cancer cells. Mol. Cancer 2009, 8, doi: 10.1186/1476-4598-8-26.
6. Brunner, T.B.; Geiger, M.; Grabenbauer, G.G.; Lang-Welzenbach, M.; Mantoni, T.S.; Cavallaro, A.; Sauer, R.; Hohenberger, W.; McKenna, W.G.; Brunner, T.B., et al. Phase I trial of the human immunodeficiency virus protease inhibitor nelfinavir and chemoradiation for locally advanced pancreatic cancer. J. Clin. Oncol. 2008, 26, 2699-2706.
7. DiCiommo, D.; Gallie, B.L.; Bremner, R. Retinoblastoma: The disease, gene and protein provide critical leads to understand cancer. Semin. Cancer Biol. 2000, 10, 255-269.
8. Gaedicke, S.; Firat-Geier, E.; Constantiniu, O.; Lucchiari-Hartz, M.; Freudenberg, M.; Galanos, C.; Niedermann, G. Antitumor effect of the human immunodeficiency virus protease inhibitor ritonavir: Induction of tumor-cell apoptosis associated with perturbation of proteasomal proteolysis. Cancer Res. 2002, 62, 6901-6908.
9. Bondar, V.M.; Sweeney-Gotsch, B.; Andreeff, M.; Mills, G.B.; McConkey, D.J. Inhibition of the phosphatidylinositol 3'-kinase-AKT pathway induces apoptosis in pancreatic carcinoma cells in vitro and in vivo. Mol. Cancer Ther. 2002, 1, 989-997.
10. Srirangam, A.; Mitra, R.; Wang, M.; Gorski, J.C.; Badve, S.; Baldridge, L.; Hamilton, J.; Kishimoto, H.; Hawes, J.; Li, L., et al. Effects of HIV protease inhibitor ritonavir on Akt-regulated cell proliferation in breast cancer. Clin. Cancer Res. 2006, 12, 1883-1896.
11. Yang, Y.; Ikezoe, T.; Nishioka, C.; Bandobashi, K.; Takeuchi, T.; Adachi, Y.; Kobayashi, M.; Takeuchi, S.; Koeffler, H.P.; Taguchi, H. NFV, an HIV-1 protease inhibitor, induces growth arrest, reduced Akt signalling, apoptosis and docetaxel sensitisation in NSCLC cell lines. Br. J. Cancer 2006, 95, 1653-1662.
12. Batchu, R.B.; Shammas, M.A.; Wang, J.Y.; Freeman, J.; Rosen, N.; Munshi, N.C. Adeno-associated virus protects the retinoblastoma family of proteins from adenoviral-induced functional inactivation. Cancer Res. 2002, 62, 2982-2985.
13. Kobayashi, H.; Suzuki, M.; Tanaka, Y.; Hirashima, Y.; Terao, T. Suppression of urokinase expression and invasiveness by urinary trypsin inhibitor is mediated through inhibition of protein kinase C- and MEK/ERK/c-Jun-dependent signaling pathways. J. Biol. Chem. 2001, 276, 2015-2022.
14. Altomare, D.A.; Testa, J.R. Perturbations of the AKT signaling pathway in human cancer. Oncogene 2005, 24, 7455-7464.
15. Tsantoulis, P.K.; Gorgoulis, V.G. Involvement of E2F transcription factor family in cancer. Eur. J. Cancer 2005, 41, 2403-2414.
16. Kariya, R.; Taura, M.; Suzu, S.; Kai, H.; Katano, H.; Okada, S. HIV protease inhibitor Lopinavir induces apoptosis of primary effusion lymphoma cells via suppression of NF-kappaB pathway. Cancer Lett. 2014, 342, 52-59.
17. Ikezoe, T.; Hisatake, Y.; Takeuchi, T.; Ohtsuki, Y.; Yang, Y.; Said, J.W.; Taguchi, H.; Koeffler, H.P. HIV-1 protease inhibitor, ritonavir: A potent inhibitor of CYP3A4, enhanced the anticancer effects of docetaxel in androgen-independent prostate cancer cells in vitro and in vivo. Cancer Res. 2004, 64, 7426-7431.
18. Sato, A.; Asano, T.; Ito, K.; Asano, T. 17-Allylamino-17-demethoxygeldanamycin and ritonavir inhibit renal cancer growth by inhibiting the expression of heat shock factor-1. Int. J. Oncol. 2012, 41, 46-52.
19. Steeg, P.S.; Steeg, P.S. Tumor metastasis: Mechanistic insights and clinical challenges. Nat. Med. 2006, 12, 895-904.
20. Pati, S.; Pelser, C.B.; Dufraine, J.; Bryant, J.L.; Reitz, M.S., Jr.; Weichold, F.F. Antitumorigenic effects of HIV protease inhibitor ritonavir: Inhibition of Kaposi sarcoma. Blood 2002, 99, 3771-3779.
21. Yamamoto, S.; Tomita, Y.; Hoshida, Y.; Morooka, T.; Nagano, H.; Dono, K.; Umeshita, K.; Sakon, M.; Ishikawa, O.; Ohigashi, H., et al. Prognostic significance of activated Akt expression in pancreatic ductal adenocarcinoma. Clin. Cancer Res. 2004, 10, 2846-2850.
22. Gatti, G.; di Biagio, A.; Casazza, R.; de Pascalis, C.; Bassetti, M.; Cruciani, M.; Vella, S.; Bassetti, D. The relationship between ritonavir plasma levels and side-effects: Implications for therapeutic drug monitoring. AIDS 1999, 13, 2083-2089.