Onconase induces autophagy sensitizing pancreatic cancer cells to gemcitabine and activates Akt/mTOR pathway in a ROS-dependent manner

Biochimica et Biophysica Acta - Molecular Cell Research

Volumn 1853, Issue 3, 2015, Pages 549-560

  Fiorini, Claudia ^a   Cordani, Marco ^a   Gotte, Giovanni ^a   Picone, Delia ^b   Donadelli, Massimo ^a  

^a UNIVERSITY OF VERONA   (Italy)

^b UNIVERSITY OF NAPLES FEDERICO II   (Italy)

Author keywords

Autophagy; Gemcitabine; Mammalian target of rapamycin (mTOR); Onconase; Pancreatic cancer; Reactive oxygen species (ROS)

Indexed keywords

BECLIN 1; GEMCITABINE; MAMMALIAN TARGET OF RAPAMYCIN; PROTEIN KINASE B; RANPIRNASE; REACTIVE OXYGEN METABOLITE; SUPEROXIDE; SUPEROXIDE DISMUTASE; UNCOUPLING PROTEIN 2; ANTINEOPLASTIC AGENT; DEOXYCYTIDINE; MTOR PROTEIN, HUMAN; ONCOPROTEIN; RIBONUCLEASE; TARGET OF RAPAMYCIN KINASE;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; AUTOLYSOSOME; AUTOPHAGOSOME; AUTOPHAGY; CANCER INHIBITION; CARCINOMA CELL; CELL GROWTH; CELL PROLIFERATION; CHEMOSENSITIZATION; CONTROLLED STUDY; DRUG MECHANISM; ENZYME ACTIVATION; GENE SILENCING; HUMAN; HUMAN CELL; PANCREAS ADENOCARCINOMA; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; ADENOCARCINOMA; ANALOGS AND DERIVATIVES; CELL CULTURE; DRUG EFFECTS; DRUG POTENTIATION; DRUG RESISTANCE; METABOLISM; PANCREAS TUMOR; PATHOLOGY; UPREGULATION;

ANURA; MAMMALIA; RANA PIPIENS;

ADENOCARCINOMA; ANTINEOPLASTIC AGENTS; AUTOPHAGY; CELLS, CULTURED; DEOXYCYTIDINE; DRUG RESISTANCE, NEOPLASM; DRUG SYNERGISM; HUMANS; ONCOGENE PROTEIN V-AKT; PANCREATIC NEOPLASMS; REACTIVE OXYGEN SPECIES; RIBONUCLEASES; SIGNAL TRANSDUCTION; TOR SERINE-THREONINE KINASES; UP-REGULATION;

EID: 84920187687     PISSN: 01674889     EISSN: 18792596     Source Type: Journal    
DOI: 10.1016/j.bbamcr.2014.12.016     Document Type: Article

References (49)

1. Ardelt W., Shogen K., Darzynkiewicz Z. Onconase and amphinase, the antitumor ribonucleases from Rana pipiens oocytes. Curr. Pharm. Biotechnol. 2008, 9:215-225.
2. Darzynkiewicz Z., Carter S.P., Mikulski S.M., Ardelt W.J., Shogen K. Cytostatic and cytotoxic effects of Pannon (P-30 Protein), a novel anticancer agent. Cell Tissue Kinet. 1988, 21:169-182.
3. Ardelt W., Mikulski S.M., Shogen K. Amino acid sequence of an anti-tumor protein from Rana pipiens oocytes and early embryos. Homology to pancreatic ribonucleases. J. Biol. Chem. 1991, 266:245-251.
4. Boix E., Wu Y., Vasandani V.M., Saxena S.K., Ardelt W., Ladner J., Youle R.J. Role of the N terminus in RNase A homologues: differences in catalytic activity, ribonuclease inhibitor interaction and cytotoxicity. J. Mol. Biol. 1996, 257:992-1007.
5. Rutkoski T.J., Raines R.T. Evasion of ribonuclease inhibitor as a determinant of ribonuclease cytotoxicity. Curr. Pharm. Biotechnol. 2008, 9:185-189.
6. Naddeo M., Vitagliano L., Russo A., Gotte G., D'Alessio G., Sorrentino S. Interactions of the cytotoxic RNase A dimers with the cytosolic ribonuclease inhibitor. FEBS Lett. 2005, 579:2663-2668.
7. Wang X.M., Guo Z.Y. Recombinant expression, different downstream processing of the disulfide-rich anti-tumor peptide Ranpirnase and its effect on the growth of human glioma cell line SHG-44. Biomed. Rep. 2013, 1:747-750.
8. Smolewski P., Witkowska M., Zwolinska M., Cebula-Obrzut B., Majchrzak A., Jeske A., Darzynkiewicz Z., Ardelt W., Ardelt B., Robak T. Cytotoxic activity of the amphibian ribonucleases onconase and r-amphinase on tumor cells from B cell lymphoproliferative disorders. Int. J. Oncol. 2014, 45:419-425.
9. Ardelt W., Ardelt B., Darzynkiewicz Z. Ribonucleases as potential modalities in anticancer therapy. Eur. J. Pharmacol. 2009, 625:181-189.
10. Saxena S.K., Gravell M., Wu Y.N., Mikulski S.M., Shogen K., Ardelt W., Youle R.J. Inhibition of HIV-1 production and selective degradation of viral RNA by an amphibian ribonuclease. J. Biol. Chem. 1996, 271:20783-20788.
11. Suhasini A.N., Sirdeshmukh R. Onconase action on tRNA(Lys3), the primer for HIV-1 reverse transcription. Biochem. Biophys. Res. Commun. 2007, 363:304-309.
12. Thorburn A., Thamm D.H., Gustafson D.L. Autophagy and cancer therapy. Mol. Pharmacol. 2014, 85:830-838.
13. Abeliovich H. Regulation of autophagy by amino acid availability in S. cerevisiae and mammalian cells. Amino Acids 2014, PMID: 24973972.
14. Donadelli M., Dando I., Zaniboni T., Costanzo C., Dalla Pozza E., Scupoli M.T., Scarpa A., Zappavigna S., Marra M., Abbruzzese A., Bifulco M., Caraglia M., Palmieri M. Gemcitabine/cannabinoid combination triggers autophagy in pancreatic cancer cells through a ROS-mediated mechanism. Cell Death Dis. 2011, 2:e152.
15. Dando I., Fiorini C., Pozza E.D., Padroni C., Costanzo C., Palmieri M., Donadelli M. UCP2 inhibition triggers ROS-dependent nuclear translocation of GAPDH and autophagic cell death in pancreatic adenocarcinoma cells. Biochim. Biophys. Acta 2013, 1833:672-679.
16. Ma T., Zhu J., Chen X., Zha D., Singhal P.C., Ding G. High glucose induces autophagy in podocytes. Exp. Cell Res. 2013, 319:779-789.
17. Fiorini C., Menegazzi M., Padroni C., Dando I., Dalla Pozza E., Gregorelli A., Costanzo C., Palmieri M., Donadelli M. Autophagy induced by p53-reactivating molecules protects pancreatic cancer cells from apoptosis. Apoptosis 2013, 18:337-346.
18. Denton D., Xu T., Kumar S. Autophagy as a pro-death pathway. Immunol. Cell Biol. 2014, 10.1038/icb.2014.85.
19. Ge L., Baskaran S., Schekman R., Hurley J.H. The protein-vesicle network of autophagy. Curr. Opin. Cell Biol. 2014, 29C:18-24.
20. Dando I., Donadelli M., Costanzo C., Dalla Pozza E., D'Alessandro A., Zolla L., Palmieri M. Cannabinoids inhibit energetic metabolism and induce AMPK-dependent autophagy in pancreatic cancer cells. Cell Death Dis. 2013, 4:e664.
21. Cecconi D., Palmieri M., Donadelli M. Proteomics in pancreatic cancer research. Proteomics 2011, 11:816-828.
22. Herreros-Villanueva M., Hijona E., Cosme A., Bujanda L. Adjuvant and neoadjuvant treatment in pancreatic cancer. World J. Gastroenterol. 2012, 18:1565-1572.
23. Donadelli M., Dalla Pozza E., Costanzo C., Scupoli M.T., Scarpa A., Palmieri M. Zinc depletion efficiently inhibits pancreatic cancer cell growth by increasing the ratio of antiproliferative/proliferative genes. J. Cell. Biochem. 2008, 104:202-212.
24. Notomista E., Cafaro V., Fusiello R., Bracale A., D'Alessio G., Di Donato A. Effective expression and purification of recombinant onconase, an antitumor protein. FEBS Lett. 1999, 463:211-215.
25. Donadelli M., Costanzo C., Beghelli S., Scupoli M.T., Dandrea M., Bonora A., Piacentini P., Budillon A., Caraglia M., Scarpa A., Palmieri M. Synergistic inhibition of pancreatic adenocarcinoma cell growth by trichostatin A and gemcitabine. Biochim. Biophys. Acta 2007, 1773:1095-1106.
26. Fiorini C., Gotte G., Donnarumma F., Picone D., Donadelli M. Bovine seminal ribonuclease triggers Beclin1-mediated autophagic cell death in pancreatic cancer cells. Biochim. Biophys. Acta 2014, 1843:976-984.
27. Gotte G., Laurents D.V., Merlino A., Picone D., Spadaccini R. Structural and functional relationships of natural and artificial dimeric bovine ribonucleases: new scaffolds for potential antitumor drugs. FEBS Lett. 2013, 587:3601-3608.
28. D'Errico G., Ercole C., Lista M., Pizzo E., Falanga A., Galdiero S., Spadaccini R., Picone D. Enforcing the positive charge of N-termini enhances membrane interaction and antitumor activity of bovine seminal ribonuclease. Biochim. Biophys. Acta 2011, 1808:3007-3015.
29. Turcotte R.F., Lavis L.D., Raines R.T. Onconase cytotoxicity relies on the distribution of its positive charge. FEBS J. 2009, 276:3846-3857.
30. Ercole C., Colamarino R.A., Pizzo E., Fogolari F., Spadaccini R., Picone D. Comparison of the structural and functional properties of RNase A and BS-RNase: a stepwise mutagenesis approach. Biopolymers 2009, 91:1009-1017.
31. Libonati M., Gotte G., Vottariello F. A novel biological actions acquired by ribonuclease through oligomerization. Curr. Pharm. Biotechnol. 2008, 9:200-209.
32. Gotte G., Mahmoud Helmy A., Ercole C., Spadaccini R., Laurents D.V., Donadelli M., Picone D. Double domain swapping in bovine seminal RNase: formation of distinct N- and C-swapped tetramers and multimers with increasing biological activities. PLoS One 2012, 7:e46804.
33. Spadaccini R., Ercole C., Graziano G., Wechselberger R., Boelens R., Picone D. Mechanism of 3D domain swapping in bovine seminal ribonuclease. FEBS J. 2014, 281:842-850.
34. Itakura E., Kishi C., Inoue K., Mizushima N. Beclin 1 forms two distinct phosphatidylinositol 3-kinase complexes with mammalian Atg14 and UVRAG. Mol. Biol. Cell 2008, 19:5360-5372.
35. Maiuri M.C., Zalckvar E., Kimchi A., Kroemer G. Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat. Rev. Mol. Cell Biol. 2007, 8:741-752.
36. Vernon P.J., Tang D. Eat-me: autophagy, phagocytosis, and reactive oxygen species signaling. Antioxid. Redox Signal. 2013, 18:677-691.
37. Ardelt B., Juan G., Burfeind P., Salomon T., Wu J.M., Hsieh T.C., Li X., Sperry R., Pozarowski P., Shogen K., Ardelt W., Darzynkiewicz Z. Onconase, an anti-tumor ribonuclease suppresses intracellular oxidative stress. Int. J. Oncol. 2007, 31:663-669.
38. Donadelli M., Dando I., Fiorini C., Palmieri M. UCP2, a mitochondrial protein regulated at multiple levels. Cell. Mol. Life Sci. 2014, 71:1171-1190.
39. Dalla Pozza E., Donadelli M., Costanzo C., Zaniboni T., Dando I., Franchini M., Arpicco S., Scarpa A., Palmieri M. Gemcitabine response in pancreatic adenocarcinoma cells is synergistically enhanced by dithiocarbamate derivatives. Free Radic. Biol. Med. 2011, 50:926-933.
40. Lanciano P., Khalfaoui-Hassani B., Selamoglu N., Ghelli A., Rugolo M., Daldal F. Molecular mechanisms of superoxide production by complex III: a bacterial versus human mitochondrial comparative case study. Biochim. Biophys. Acta 2013, 1827:1332-1339.
41. Papa L., Manfredi G., Germain D. SOD1, an unexpected novel target for cancer therapy. Genes Cancer 2014, 5:15-21.
42. Lustgarten M.S., Bhattacharya A., Muller F.L., Jang Y.C., Shimizu T., Shirasawa T., Richardson A., Van Remmen H. Complex I generated, mitochondrial matrix-directed superoxide is released from the mitochondria through voltage dependent anion channels. Biochem. Biophys. Res. Commun. 2012, 422:515-521.
43. Porta C., Paglino C., Mosca A. Targeting PI3K/Akt/mTOR signaling in cancer. Front. Oncol. 2014, 4:64.
44. Chen S., Ren Q., Zhang J., Ye Y., Zhang Z., Xu Y., Guo M., Ji H., Xu C., Gu C., Gao W., Huang S., Chen L. N-acetyl-L-cysteine protects against cadmium-induced neuronal apoptosis by inhibiting ROS-dependent activation of Akt/mTOR pathway in mouse brain. Neuropathol. Appl. Neurobiol. 2014, 40(6):759-777.
45. Yang J., Li T.Z., Xu G.H., Luo B.B., Chen Y.X., Zhang T. Low-concentration capsaicin promotes colorectal cancer metastasis by triggering ROS production and modulating Akt/mTOR and STAT-3 pathways. Neoplasma 2013, 60:364-372.
46. Son Y.O., Pratheeshkumar P., Wang L., Wang X., Fan J., Kim D.H., Lee J.Y., Zhang Z., Lee J.C., Shi X. Reactive oxygen species mediate Cr(VI)-induced carcinogenesis through PI3K/AKT-dependent activation of GSK-3beta/beta-catenin signaling. Toxicol. Appl. Pharmacol. 2013, 271:239-248.
47. Carpenter R.L., Jiang Y., Jing Y., He J., Rojanasakul Y., Liu L.Z., Jiang B.H. Arsenite induces cell transformation by reactive oxygen species, AKT, ERK1/2, and p70S6K1. Biochem. Biophys. Res. Commun. 2011, 414:533-538.
48. Chen L., Xu B., Liu L., Luo Y., Zhou H., Chen W., Shen T., Han X., Kontos C.D., Huang S. Cadmium induction of reactive oxygen species activates the mTOR pathway, leading to neuronal cell death. Free Radic. Biol. Med. 2011, 50:624-632.
49. Duvel K., Yecies J.L., Menon S., Raman P., Lipovsky A.I., Souza A.L., Triantafellow E., Ma Q., Gorski R., Cleaver S., Vander Heiden M.G., MacKeigan J.P., Finan P.M., Clish C.B., Murphy L.O., Manning B.D. Activation of a metabolic gene regulatory network downstream of mTOR complex 1. Mol. Cell 2010, 39:171-183.