The Combination of Rapamycin and Resveratrol Blocks Autophagy and Induces Apoptosis in Breast Cancer Cells

Journal of Cellular Biochemistry

Volumn 116, Issue 3, 2015, Pages 450-457

  Alayev, Anya ^a   Berger, Sara Malka ^a   Kramer, Melissa Y ^a   Schwartz, Naomi S ^a   Holz, Marina K ^a,b,c  

^a YESHIVA UNIVERSITY   (United States)

^b ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

^c ALBERT EINSTEIN CANCER CENTER   (United States)

Author keywords

Apoptosis; Autophagy; mTORC1; Rapamycin; Resveratrol

Indexed keywords

BAFILOMYCIN A1; ESTROGEN RECEPTOR ALPHA; INITIATION FACTOR 4B; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE; PROTEIN KINASE B; RAPAMYCIN; RESVERATROL; SURVIVIN; MECHANISTIC TARGET OF RAPAMYCIN COMPLEX 1; MULTIPROTEIN COMPLEX; S6 KINASE; STILBENE DERIVATIVE; TARGET OF RAPAMYCIN KINASE;

APOPTOSIS; ARTICLE; AUTOPHAGOSOME; AUTOPHAGY; BREAST ADENOCARCINOMA; BREAST CANCER CELL LINE; CANCER GROWTH; CELL DENSITY; CELL DIVISION; CELL PROLIFERATION; CELL SURVIVAL; CELL VACUOLE; CONTROLLED STUDY; ENZYME ACTIVATION; ESTROGEN RECEPTOR POSITIVE BREAST CANCER; HUMAN; HUMAN CELL; MCF 7 CELL LINE; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; SIGNAL TRANSDUCTION; TRANSLATION INITIATION; TRIPLE NEGATIVE BREAST CANCER; UPREGULATION; BIOLOGICAL MODEL; BREAST TUMOR; DRUG EFFECTS; DRUG POTENTIATION; FEMALE; METABOLISM; PATHOLOGY; TUMOR CELL LINE;

APOPTOSIS; AUTOPHAGY; BREAST NEOPLASMS; CELL LINE, TUMOR; CELL PROLIFERATION; DRUG SYNERGISM; ESTROGEN RECEPTOR ALPHA; FEMALE; HUMANS; MODELS, BIOLOGICAL; MULTIPROTEIN COMPLEXES; PROTO-ONCOGENE PROTEINS C-AKT; RIBOSOMAL PROTEIN S6 KINASES; SIGNAL TRANSDUCTION; SIROLIMUS; STILBENES; TOR SERINE-THREONINE KINASES; UP-REGULATION;

EID: 84941068921     PISSN: 07302312     EISSN: 10974644     Source Type: Journal    
DOI: 10.1002/jcb.24997     Document Type: Article

References (26)

1. Alayev A, Doubleday PF, Berger SM, Ballif BA, Holz MK,. 2014. Phosphoproteomics reveals resveratrol-dependent inhibition of Akt/mTORC1/S6K1 signaling. J Proteome Res DOI: 10.1021/pr500714a.
2. Alayev A, Holz MK,. 2013. mTOR signaling for biological control and cancer. J Cell Physiol 228 (8): 1658-1664.
3. Alayev A, Sun Y, Snyder RB, Berger SM, Yu JJ, Holz MK,. 2014. Resveratrol prevents rapamycin-induced upregulation of autophagy and selectively induces apoptosis in TSC2-deficient cells. Cell Cycle 13 (3): 371-382.
4. Armour SM, Baur JA, Hsieh SN, Land-Bracha A, Thomas SM, Sinclair DA,. 2009. Inhibition of mammalian S6 kinase by resveratrol suppresses autophagy. Aging (Albany NY) 1 (6): 515-528.
5. Baehrecke EH,. 2005. Autophagy: Dual roles in life and death? Nat Rev Mol Cell Biol 6 (6): 505-510.
6. Banerjee S, Bueso-Ramos C, Aggarwal BB,. 2002. Suppression of 7,12-dimethylbenz(a) anthracene-induced mammary carcinogenesis in rats by resveratrol: Role of nuclear factor-kappaB, cyclooxygenase 2, and matrix metalloprotease 9. Cancer Res 62 (17): 4945-4954.
7. Baselga J, Campone M, Piccart M, Burris HA, 3rd, Rugo HS, Sahmoud T, Noguchi S, Gnant M, Pritchard KI, Lebrun F, Beck JT, Ito Y, Yardley D, Deleu I, Perez A, Bachelot T, Vittori L, Xu Z, Mukhopadhyay P, Lebwohl D, Hortobagyi GN,. 2012. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med 366 (6): 520-529.
8. Bishayee A,. 2009. Cancer prevention and treatment with resveratrol: From rodent studies to clinical trials. Cancer Prev Res (Phila) 2 (5): 409-418.
9. Carter LG, D'Orazio JA, Pearson KJ,. 2014. Resveratrol and cancer: Focus on in vivo evidence. Endocr Relat Cancer 21 (3): R209-R225.
10. Ciruelos Gil EM,. 2014. Targeting the PI3K/AKT/mTOR pathway in estrogen receptor-positive breast cancer. Cancer Treat Rev 40 (7): 862-871.
11. Demidenko ZN, Blagosklonny MV,. 2009. At concentrations that inhibit mTOR, resveratrol suppresses cellular senescence. Cell Cycle 8 (12): 1901-1904.
12. Dorrello NV, Peschiaroli A, Guardavaccaro D, Colburn NH, Sherman NE, Pagano M,. 2006. S6K1- and betaTRCP-mediated degradation of PDCD4 promotes protein translation and cell growth. Science 314 (5798): 467-471.
13. Esclatine A, Chaumorcel M, Codogno P,. 2009. Macroautophagy signaling and regulation. Curr Top Microbiol Immunol 335: 33-70.
14. Gehm BD, McAndrews JM, Chien PY, Jameson JL,. 1997. Resveratrol, a polyphenolic compound found in grapes and wine, is an agonist for the estrogen receptor. Proc Natl Acad Sci USA 94 (25): 14138-14143.
15. Holz MK,. 2012. The role of S6K1 in ER-positive breast cancer. Cell Cycle 11 (17): 3159-3165.
16. Liang J, Shao SH, Xu ZX, Hennessy B, Ding Z, Larrea M, Kondo S, Dumont DJ, Gutterman JU, Walker CL, Slingerland JM, Mills GB,. 2007. The energy sensing LKB1-AMPK pathway regulates p27(kip1) phosphorylation mediating the decision to enter autophagy or apoptosis. Nat Cell Biol 9 (2): 218-224.
17. Maruani DM, Spiegel TN, Harris EN, Shachter AS, Unger HA, Herrero-Gonzalez S, Holz MK,. 2012. Estrogenic regulation of S6K1 expression creates a positive regulatory loop in control of breast cancer cell proliferation. Oncogene 31 (49): 5073-5080.
18. O'Reilly KE, Rojo F, She QB, Solit D, Mills GB, Smith D, Lane H, Hofmann F, Hicklin DJ, Ludwig DL, Baselga J, Rosen N,. 2006. mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer Res 66 (3): 1500-1508.
19. Rabinowitz JD, White E,. 2010. Autophagy and metabolism. Science 330 (6009): 1344-1348.
20. Rubinsztein DC, Codogno P, Levine B,. 2012. Autophagy modulation as a potential therapeutic target for diverse diseases. Nat Rev Drug Discov 11 (9): 709-730.
21. Schmadeka R, Harmon BE, Singh M., 2014. Triple-negative breast carcinoma: current and emerging concepts. Am J Clin Pathol 141 (4): 462-477.
22. Sun SY, Rosenberg LM, Wang X, Zhou Z, Yue P, Fu H, Khuri FR,. 2005. Activation of Akt and eIF4E survival pathways by rapamycin-mediated mammalian target of rapamycin inhibition. Cancer Res 65 (16): 7052-7058.
23. Whitsett T, Carpenter M, Lamartiniere CA,. 2006. Resveratrol, but not EGCG, in the diet suppresses DMBA-induced mammary cancer in rats. J Carcinog 5: 15.
24. Yamnik RL, Digilova A, Davis DC, Brodt ZN, Murphy CJ, Holz MK,. 2009. S6 kinase 1 regulates estrogen receptor alpha in control of breast cancer cell proliferation. J Biol Chem 284 (10): 6361-6369.
25. Yamnik RL, Holz MK,. 2010. mTOR/S6K1 and MAPK/RSK signaling pathways coordinately regulate estrogen receptor alpha serine 167 phosphorylation. FEBS Lett 584 (1): 124-128.
26. Yu J, Parkhitko A, Henske EP,. 2011. Autophagy: an 'Achilles' heel of tumorigenesis in TSC and LAM. Autophagy 7 (11): 1400-1401.