Inhibition of autophagy potentiates pemetrexed and simvastatin-induced apoptotic cell death in malignant mesothelioma and non-small cell lung cancer cells

Oncotarget

Volumn 6, Issue 30, 2015, Pages 29482-29496

  Hwang, Ki Eun ^a   Kim, Young Suk ^a   Jung, Jae Wan ^a   Kwon, Su Jin ^a   Park, Do Sim ^b   Cha, Byong Ki ^c   Oh, Seon Hee ^d   Yoon, Kwon Ha ^b   Jeong, Eun Taik ^a   Kim, Hak Ryul ^a  

^a Wonkwang University School of Medicine   (South Korea)

^b Wonkwang University   (South Korea)

^c Chonbuk National University Medical School   (South Korea)

^d Chosun University   (South Korea)

Author keywords

Apoptosis; Autophagy; Pemetrexed; Simvastatin

Indexed keywords

3 METHYLADENINE; CASPASE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; MAMMALIAN TARGET OF RAPAMYCIN; PEMETREXED; PROTEIN KINASE B; SIMVASTATIN; 3-METHYLADENINE; ADENINE; ANTINEOPLASTIC AGENT; ATG5 PROTEIN, HUMAN; AUTOPHAGY RELATED PROTEIN 5; BAFILOMYCIN A; MACROLIDE; MICROTUBULE ASSOCIATED PROTEIN; MTOR PROTEIN, HUMAN; PEPSTATIN; PROTEIN KINASE INHIBITOR; TARGET OF RAPAMYCIN KINASE;

ANIMAL EXPERIMENT; ANIMAL MODEL; APOPTOSIS; ARTICLE; AUTOPHAGY; CANCER CELL; CELL PROLIFERATION; CONTROLLED STUDY; DRUG POTENTIATION; HUMAN; HUMAN CELL; LUNG CANCER; MALIGNANT MESOTHELIOMA; MOUSE; NON SMALL CELL LUNG CANCER; NONHUMAN; TUMOR XENOGRAFT; ANALOGS AND DERIVATIVES; ANIMAL; ANTAGONISTS AND INHIBITORS; CARCINOMA, NON-SMALL-CELL LUNG; DOSE RESPONSE; DRUG EFFECTS; DRUG SCREENING; GENETIC TRANSFECTION; GENETICS; LUNG NEOPLASMS; MESOTHELIOMA; METABOLISM; NUDE MOUSE; PATHOLOGY; RNA INTERFERENCE; SIGNAL TRANSDUCTION; TIME FACTOR; TUMOR CELL LINE; TUMOR VOLUME;

ADENINE; AMP-ACTIVATED PROTEIN KINASES; ANIMALS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; APOPTOSIS; AUTOPHAGY; AUTOPHAGY-RELATED PROTEIN 5; CARCINOMA, NON-SMALL-CELL LUNG; CELL LINE, TUMOR; CELL PROLIFERATION; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG SYNERGISM; HUMANS; LUNG NEOPLASMS; MACROLIDES; MESOTHELIOMA; MICE, NUDE; MICROTUBULE-ASSOCIATED PROTEINS; PEMETREXED; PEPSTATINS; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS C-AKT; RNA INTERFERENCE; SIGNAL TRANSDUCTION; SIMVASTATIN; TIME FACTORS; TOR SERINE-THREONINE KINASES; TRANSFECTION; TUMOR BURDEN; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84945115866     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.5022     Document Type: Article

References (42)

1. Spiro SG, Tanner NT, Silvestri GA, Janes SM, Lim E, Vansteenskiste JF, Pirker R. Lung cancer: progress in diagnosis, staging and therapy. Respirology. 2010; 15:44-50.
2. Hotta K, Matsuo K, Ueoka H, Kiura K, Tabata M, Tanimoto M. Meta-analysis of randomized clinical trials comparing Cisplatin to Carboplatin in patients with advanced nonsmall-cell lung cancer. Journal of Clinical Oncology. 2004; 22:3852-3859.
3. Belli C, Fennell D, Giovannini M, Gaudino G, Mutti L. Malignant pleural mesothelioma: current treatments and emerging drugs. Expert Opinion on Emerging Drugs. 2009; 14:423-437.
4. Levine B, Klionsky DJ. Development by self-digestion: molecular mechanisms and biological functions of autophagy. Developmental Cell. 2004; 6:463-477.
5. Meijer AJ, Codogno P. Regulation and role of autophagy in mammalian cells. International Journal of Biochemistry & Cell Biology. 2004; 36:2445-2462.
6. Yoshimori T. Autophagy: a regulated bulk degradation process inside cells. Biochemical and Biophysical Research Communications. 2004; 313:453-458.
7. Eisenberg-Lerner A, Bialik S, Simon HU, Kimchi A. Life and death partners: apoptosis, autophagy and the cross-talk between them. Cell Death and Differentiation. 2009; 16:966-975.
8. Amaravadi RK, Yu D, Lum JJ, Bui T, Christophorou MA, Evan GI, Thomas-Tikhonenko A, Thompson CB. Autophagy inhibition enhances therapy-induced apoptosis in a Myc-induced model of lymphoma. Journal of Clinical Investigation. 2007; 117:326-336.
9. Vogelzang NJ, Rusthoven JJ, Symanowski J, Denham C, Kaukel E, Ruffie P, GGatzemeier U, Boyer M, Emri S, Manegold C, Niyikiza C, Paoletti P. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. Journal of Clinical Oncology. 2003; 21:2636-2644.
10. Scagliotti GV, Parikh P, von Pawel J, Biesma B, Vansteenkiste J, Manegold C, Serwatowski P, Gatzemeier U, Digumarti R, Zukin M, Lee JS, Mellemgaard A, Park K, et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naïve patients with advanced-stage non-small-cell lung cancer. Journal of Clinical Oncology. 2008; 26:3543-3551.
11. Lim JU, Woo IS, Jung YH, Byeon JH, Park CK, Kim TJ, Kim HR. Transformation into large-cell neuroendocrine carcinoma associated with acquired resistance to erlotinib in nonsmall cell lung cancer. Korean Journal of Internal Medicine. 2014; 29:830-833.
12. Shih C, Chen VJ, Gossett LS, Gates SB, MacKellar WC, Habeck LL, Shackelford KA, Mendelsohn LG, Soose DJ, Patel VF, Andis SL, Bewley JR, Rayl EA, et al. LY231514, a pyrrolo[2,3-d]pyrimidine-based antifolate that inhibits multiple folate-requiring enzymes. Cancer Research. 1997; 57:1116-1123.
13. Zhang D, Ochi N, Takigawa N, Tanimoto Y, Chen Y, Ichihara E, Hotta K, Tabata M, Tanimoto M, Kiura K. Establishment of pemetrexed-resistant non-small cell lung cancer cell lines. Cancer Letters. 2011; 309:228-235.
14. Ramirez JM, Ocio EM, San Miguel JF, Pandiella A. Pemetrexed acts as an antimyeloma agent by provoking cell cycle blockade and apoptosis. Leukemia. 2007; 21:797-804.
15. Lu X, Errington J, Curtin NJ, Lunec J, Newell DR. The impact of p53 status on cellular sensitivity to antifolate drugs. Clinical Cancer Research. 2001; 7:2114-2123.
16. Vandermeers F, Hubert P, Delvenne P, Mascaux C, Grigoriu B, Burny A, Scherpereel A, Willems L. Valproate, in combination with pemetrexed and cisplatin, provides additional efficacy to the treatment of malingnant mesothelioma. Clinical Cancer Research. 2009; 15:2818-2828.
17. Bareford MD, Park MA, Yacoub A, Hamed HA, Tang Y, Cruickshanks N, Eulitt P, Hubbard N, Tye G, Burow ME, Fisher PB, Moran RG, Nephew KP, et al. Sorafenib enhances pemetrexed cytotoxicity through an autophagydependent mechanism in cancer cells. Cancer Research. 2011; 71:4955-4967.
18. Goldstein JL, Brown MS. Regulation of the mevalonate pathway. Nature. 1990; 343:425-430.
19. Chan KK, Oza AM, Siu LL. The statins as anticancer agents. Clinical Cancer Research. 2003; 9:10-19.
20. Demierre MF, Higgins PD, Gruber SB, Haw E, Lippman SM. Statins and cancer prevention. Nature Reviews Cancer. 2005; 5:930-942.
21. Hwang KE, Na KS, Park DS, Choi KH, Kim BR, Shim H, Jeong ET, Kim HR. Apoptotic induction by simvastatin in human lung cancer A549 cells via Akt signaling dependent down-regulation of surviving. Investigational New Drugs. 2011; 29:945-952.
22. Yang PM, Liu YL, Lin YC, Shun CT, Wu MS, Chen CC. Inhibition of autophagy enhances anticancer effects of atrovastatin in digestive malignancies. Cancer Research. 2010; 70:7699-7709.
23. Sun JM, Lee KW, Kim JH, Kim YJ, Yoon HI, Lee JH, Lee CT, Lee JS. Efficacy and toxicity of pemetrexed as a third-line treatment of non-small cell lung cancer. Japanese Journal of Clinical Oncology. 2009; 39:27-32.
24. Kim KH, Song SY, Lim KH, Han SS, Kim SH, Cho JH, Park CW, Lee S, Lee HY. Interstitial pneumonitis after treatment with pemetrexed for non-small cell lung cancer. Cancer Research and Treatment. 2013; 45:74-77.
25. Hwang KE, Kim YS, Hwang YR, Kwon SJ, Park DS, Cha BK, Kim BR, Yoon KH, Jeong ET, Kim HR. Enhanced apoptosis by pemetrexed and simvastatin in malignant mesothelioma and lung cancer cells by reactive oxygen species-dependent mitochondrial dysfunction and Bim induction. International Journal of Oncology. 2014; 45:1769-1777.
26. Rothbart SB, Racanelli AC, Moran RG. Pemetrexed indirectly activates the metabolic kinase AMPK in human carcinomas. Cancer Research. 2010; 70:10299-10309.
27. Jeong EH, Choi HS, Lee TG, Kim HR, Kim CH. Dual inhibition of PI3K/Akt/mTOR pathway and role of autophagy in non-small cell lung cancer cells. Tuberculosis and Respiratory Diseases. 2012; 72:343-351.
28. Huang S, Sinicrope FA. Celecoxib-induced apoptosis is enhanced by ABT-737 and by inhibition of autophagy in human colorectal cancer cells. Autophagy. 2010; 6:256-269.
29. Zhang XD, Qi L, Wu JC, Qin ZH. DRAM1 regulates autophagy flux through lysosomes. PLoS One. 2013; 8:e63245.
30. Boya P, Gonzalez-Polo RA, Casares N, Perfettini JL, Dessen P, Larochette N, Metivier D, Meley D. Inhibition of macroautophagy triggers apoptosis. Molecular Biology of the Cell. 2005; 25:1025-1040.
31. Schulze-Bergkamen H, Krammer PH. Apotosis in cancerimplications for therapy. Seminars in Oncology. 2004; 31:90-119.
32. Del Bufalo D, Desideri M, De Luca T, Di Martile M, Gabellini C, Monica V, Busso S, Eramo A, De Maria R, Milella M, Trisciuoglio D. Histone deacetylase inhibition synergistically enhances pemetrexed cytotoxicity through induction of apoptosis and autophagy in non-small cell lung cancer. Molecular Cancer. 2014; 13:230.
33. Park JH, Lee YR, So HS, Lee KK, Lee SY, Moon SR, Jo HJ, Jeong K, Kwon KB, Yang SH. The role of autophagy induced by pemetrexed in lung adenocarcinoma cells. Oncology Reports. 2014; 31:2365-2370.
34. Abedin MJ, Wang D, McDonnell MA, Lehmann U, Kelekar A. Autophagy delays apoptotic death in breast cancer cells following DNA damage. Cell Death and Differentiation. 2007; 14:500-510.
35. Choi HS, Jeong EH, Lee TG, Kim SY, Kim HR, Kim CH. Autophagy inhibition with monensin enhances cell cycle arrest and apoptosis induced by mTOR or epidermal growth factor receptor inhibitors in lung cancer cells. Tuberculosis and Respiratory Diseases. 2013; 75:9-17.
36. Maiuri MC, Zalckvar E, Kimchi A, Kroemer G. Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nature Reviews Molecular Cell Biology. 2007; 8:741-752.
37. Amaravadi RK, Thompson CB. The roles of therapyinduced autophagy and necrosis in cancer treatment. Clinical Cancer Reserch. 2007; 13:7171-7179.
38. Maiuri MC, Zalckvar E, Kimchi A, Kroemer G. Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nature Reviews Molecular Cell Biology. 2007; 8:741-752.
39. Pankiv S, Clausen TH, Lamark T, Brech A, Bruun JA, Outzen H, Overvatn A, Biorkor G, Johansen T. p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. Journal of Biological Chemistry. 2007; 282:24131-24145.
40. Mathew R, Karp CM, Beaudoin B, Vuong N, Chen G, Chen HY, Bray K, Reddy A, Bhanot G, Gelinas C, Dipaola RS, Karantza-Wadsworth V, White E. Autophagy suppresses tumorigenesis through elimination of p62. Cell. 2009; 137:1062-1075.
41. Floto RA, Sarkar S, Perlstein EO, Kampmann B, Schreiber SL, Rubinsztein DC. Small molecule enhancers of rapamycin-induced TOR inhibition promote autophagy, reduce toxicity in Huntington's disease models and enhance killing of mycobacteria by macrophages. Autophagy. 2007; 3:620-622.
42. Rosenbluth JM, Pietenpol JA. mTOR regulates autophagyassociated genes downstream of p73. Autophagy. 2009; 5:114-116.