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Cannabinoids inhibit energetic metabolism and induce AMPK-dependent autophagy in pancreatic cancer cells

Dando, I, Donadelli, M, Costanzo, C, Dalla Pozza, E, D'Alessandro, A, Zolla, L, Palmieri, M·2013·Cell Death & Disease
DOI 10.1038/cddis.2013.151PMC PMC3698539
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Figure 1 Effect of cannabinoids on key metabolic proteins. Western blot analyses of (a) phospho-AMPK, (b) phospho-p70S6K, (c) HIF-1 alpha, and (d) pyruvate dehydrogenase kinase (PDHK) were performed after treatment of Panc1 cells for 1, 12, and 24 h with 200 μM GW or ACPA. The bands were scanned as digital peaks and the areas of the peaks were calculated in arbitrary units, as described in Materials and Methods. The value of α-tubulin was used as a normalizing factor and quantifications represent the ratio phosphorylated/total protein. Quantification values are the means of three independent experiments (±S.D.). Statistical analysis: *P<0.05, **P<0.01, and ***P<0.001
Figure 1 Effect of cannabinoids on key metabolic proteins. Western blot analyses of (a) phospho-AMPK, (b) phospho-p70S6K, (c) HIF-1 alpha, and (d) pyruvate dehydrogenase kinase (PDHK) were performed after treatment of Panc1 cells for 1, 12, and 24 h with 200 μM GW or ACPA. The bands were scanned as digital peaks and the areas of the peaks were calculated in arbitrary units, as described in Materials and Methods. The value of α-tubulin was used as a normalizing factor and quantifications represent the ratio phosphorylated/total protein. Quantification values are the means of three independent experiments (±S.D.). Statistical analysis: *P<0.05, **P<0.01, and ***P<0.001CC BY-NC-ND · PubMed Central
Figure 2 Role of AMPK in cannabinoid-induced autophagy. Western blot analysis of (a) LC3-II after treatment of Panc1 cells for 12 h with 200 μM GW or ACPA and 20 μM CC, and of (b) p-p70S6K and (c) LC3-II after treatment of Panc1 cells for 12 h with 200 μM GW or ACPA, in the presence or absence of the expression vectors for the AMPK wt or mutant R531G gamma-2 subunit. The bands were scanned as digital peaks and the areas of the peaks were calculated in arbitrary units, as described in Materials and Methods. The value of α-tubulin was used as a normalizing factor. Values are the means of three independent experiments (±S.D.). (d) AMP/ATP ratio was measured after 12 h treatment with 200 μM GW or ACPA, in the absence or presence of a pre-treatment for 1 h with 20 mM NAC, as reported in Materials and Methods. Values are the means of three independent experiments (±S.D.). Statistical analysis: *P<0.05, **P<0.01, and ***P<0.001
Figure 2 Role of AMPK in cannabinoid-induced autophagy. Western blot analysis of (a) LC3-II after treatment of Panc1 cells for 12 h with 200 μM GW or ACPA and 20 μM CC, and of (b) p-p70S6K and (c) LC3-II after treatment of Panc1 cells for 12 h with 200 μM GW or ACPA, in the presence or absence of the expression vectors for the AMPK wt or mutant R531G gamma-2 subunit. The bands were scanned as digital peaks and the areas of the peaks were calculated in arbitrary units, as described in Materials and Methods. The value of α-tubulin was used as a normalizing factor. Values are the means of three independent experiments (±S.D.). (d) AMP/ATP ratio was measured after 12 h treatment with 200 μM GW or ACPA, in the absence or presence of a pre-treatment for 1 h with 20 mM NAC, as reported in Materials and Methods. Values are the means of three independent experiments (±S.D.). Statistical analysis: *P<0.05, **P<0.01, and ***P<0.001CC BY-NC-ND · PubMed Central
Figure 3 Effect of cannabinoids on glycolysis. Panc1 were treated for 12 h with (a) GW or (b) ACPA and the metabolites analysis was performed as reported in Materials and Methods.FDP, fructose 1,6-bisphosphate; F6P, fructose-6-phosphate; G3P, glyceraldehyde-3-phosphate; G6P, glucose-6-phosphate; LACT, lactate; PEP, phosphoenolpyruvate. (c) Glucose consumption was measured as reported in Materials and Methods. Values are the means of three independent experiments (±S.D.). (d) PKM2 activity was performed after treatment of Panc1 cells for 12 or 24 h with 200 μM GW or ACPA, as reported in Materials and Methods. Values are the means of three independent experiments (±S.D.). Statistical analysis: *P<0.05, **P<0.01, and ***P<0.001
Figure 3 Effect of cannabinoids on glycolysis. Panc1 were treated for 12 h with (a) GW or (b) ACPA and the metabolites analysis was performed as reported in Materials and Methods.FDP, fructose 1,6-bisphosphate; F6P, fructose-6-phosphate; G3P, glyceraldehyde-3-phosphate; G6P, glucose-6-phosphate; LACT, lactate; PEP, phosphoenolpyruvate. (c) Glucose consumption was measured as reported in Materials and Methods. Values are the means of three independent experiments (±S.D.). (d) PKM2 activity was performed after treatment of Panc1 cells for 12 or 24 h with 200 μM GW or ACPA, as reported in Materials and Methods. Values are the means of three independent experiments (±S.D.). Statistical analysis: *P<0.05, **P<0.01, and ***P<0.001CC BY-NC-ND · PubMed Central
Figure 4 Cannabinoids induce AMPK-dependent GAPDH nuclear translocation. Representative confocal images of GAPDH translocation in Panc1 cell nuclei after 12 h treatment with 200 μM GW or ACPA in the absence or presence of a pre-treatment for 1 h with 20 mM NAC or 20 μM C.C. Values are the means of three independent experiments (±S.D.)
Figure 4 Cannabinoids induce AMPK-dependent GAPDH nuclear translocation. Representative confocal images of GAPDH translocation in Panc1 cell nuclei after 12 h treatment with 200 μM GW or ACPA in the absence or presence of a pre-treatment for 1 h with 20 mM NAC or 20 μM C.C. Values are the means of three independent experiments (±S.D.)CC BY-NC-ND · PubMed Central
Figure 5 Effect of cannabinoids on Krebs cycle. Panc1 were treated for 12 h with 200 μM (a) GW or (b) ACPA and the metabolites analysis was performed as reported in Materials and Methods.KET, alpha-ketoglutarate; MA, malate; SUCC, succinate. (c) NADH was measured after 12 h treatment with 200 μM GW or ACPA in the presence or absence of a pre-treatment for 1 h with 20 mM NAC, as reported in Materials and Methods. Values are the means of three independent experiments (±S.D.). Statistical analysis: *P<0.05, **P<0.01, and ***P<0.001
Figure 5 Effect of cannabinoids on Krebs cycle. Panc1 were treated for 12 h with 200 μM (a) GW or (b) ACPA and the metabolites analysis was performed as reported in Materials and Methods.KET, alpha-ketoglutarate; MA, malate; SUCC, succinate. (c) NADH was measured after 12 h treatment with 200 μM GW or ACPA in the presence or absence of a pre-treatment for 1 h with 20 mM NAC, as reported in Materials and Methods. Values are the means of three independent experiments (±S.D.). Statistical analysis: *P<0.05, **P<0.01, and ***P<0.001CC BY-NC-ND · PubMed Central
Figure 6 Effect of cannabinoids on glutamine metabolism. (a) The analyses of glutamine uptake and glutamate release were performed after treatment of Panc1 cells for 12 h with 200 μM GW or ACPA. (b) Western blot analysis was performed using total protein extracts of Panc1 cells treated for 1, 12 and 24 h with 200 μM GW or ACPA. The bands were scanned as digital peaks and the areas of the peaks were calculated in arbitrary units, as described in Materials and Methods. The value of α-tubulin was used as a normalizing factor and quantifications represent the ratio phosphorylated/total protein. Values are the means of three independent experiments (±S.D.). (c) C-Myc activity was analysed after treatment for 1, 12 and 24 h with 200 μM GW or ACPA. Values are the means of three independent experiments (±S.D.). Statistical analysis: *P<0.05, **P<0.01, and ***P<0.001
Figure 6 Effect of cannabinoids on glutamine metabolism. (a) The analyses of glutamine uptake and glutamate release were performed after treatment of Panc1 cells for 12 h with 200 μM GW or ACPA. (b) Western blot analysis was performed using total protein extracts of Panc1 cells treated for 1, 12 and 24 h with 200 μM GW or ACPA. The bands were scanned as digital peaks and the areas of the peaks were calculated in arbitrary units, as described in Materials and Methods. The value of α-tubulin was used as a normalizing factor and quantifications represent the ratio phosphorylated/total protein. Values are the means of three independent experiments (±S.D.). (c) C-Myc activity was analysed after treatment for 1, 12 and 24 h with 200 μM GW or ACPA. Values are the means of three independent experiments (±S.D.). Statistical analysis: *P<0.05, **P<0.01, and ***P<0.001CC BY-NC-ND · PubMed Central
Figure 7 Schematic representation of the model describing the inhibition of energetic metabolism and the induction of AMPK-induced autophagic cell death by cannabinoids
Figure 7 Schematic representation of the model describing the inhibition of energetic metabolism and the induction of AMPK-induced autophagic cell death by cannabinoidsCC BY-NC-ND · PubMed Central

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  1. Hermanson DJ, Cannabinoids Marnett LJ . endocannabinoids, and cancer. Cancer Metastasis Rev 2011; 30: 599–612. · DOI
  2. Pisanti S, Bifulco M . Endocannabinoid system modulation in cancer biology and therapy. Pharmacol Res 2009; 60: 107–116. · DOI
  3. Pisanti S, Malfitano AM, Grimaldi C, Santoro A, Gazzerro P, Laezza C et al. Use of cannabinoid receptor agonists in cancer therapy as palliative and curative agents. Best Pract Res Clin Endocrinol Metab 2009; 23: 117–131. · DOI
  4. Velasco G, Carracedo A, Blazquez C, Lorente M, Aguado T, Haro A et al. Cannabinoids and gliomas. Mol Neurobiol 2007; 36: 60–67. · DOI
  5. Qamri Z, Preet A, Nasser MW, Bass CE, Leone G, Barsky SH et al. Synthetic cannabinoid receptor agonists inhibit tumor growth and metastasis of breast cancer. Mol Cancer Ther 2009; 8: 3117–3129. · DOI
  6. Sarfaraz S, Afaq F, Adhami VM, Mukhtar H . Cannabinoid receptor as a novel target for the treatment of prostate cancer. Cancer Res 2005; 65: 1635–1641. · DOI
  7. Proto MC, Gazzerro P, Di Croce L, Santoro A, Malfitano AM, Pisanti S et al. Interaction of endocannabinoid system and steroid hormones in the control of colon cancer cell growth. J Cell Physiol 2012; 227: 250–258. · DOI
  8. Guindon J, Hohmann AG . The endocannabinoid system and cancer: therapeutic implication. Br J Pharmacol 2011; 163: 1447–1463. · DOI
  9. De Petrocellis L, Melck D, Palmisano A, Bisogno T, Laezza C, Bifulco M et al. The endogenous cannabinoid anandamide inhibits human breast cancer cell proliferation. Proc Natl Acad Sci USA 1998; 95: 8375–8380. · DOI
  10. Donadelli M, Dando I, Zaniboni T, Costanzo C, Dalla Pozza E, Scupoli MT et al. Gemcitabine/cannabinoid combination triggers autophagy in pancreatic cancer cells through a ROS-mediated mechanism. Cell Death Dis 2011; 2: e152. · DOI
  11. Salazar M, Carracedo A, Salanueva IJ, Hernandez-Tiedra S, Lorente M, Egia A et al. Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells. J Clin Invest 2009; 119: 1359–1372. · DOI
  12. Levine B . Cell biology: autophagy and cancer. Nature 2007; 446: 745–747. · DOI
  13. Vara D, Salazar M, Olea-Herrero N, Guzman M, Velasco G, Diaz-Laviada I . Anti-tumoral action of cannabinoids on hepatocellular carcinoma: role of AMPK-dependent activation of autophagy. Cell Death Differ 2011; 18: 1099–1111. · DOI
  14. Hardie DG . AMP-activated protein kinase: an energy sensor that regulates all aspects of cell function. Genes Dev 2011; 25: 1895–1908. · DOI · Paper page
  15. Hawley SA, Boudeau J, Reid JL, Mustard KJ, Udd L, Makela TP et al. Complexes between the LKB1 tumor suppressor, STRAD alpha/beta and MO25 alpha/beta are upstream kinases in the AMP-activated protein kinase cascade. J Biol 2003; 2: 28. · DOI
  16. Hurley RL, Anderson KA, Franzone JM, Kemp BE, Means AR, Witters LA . The Ca2+/calmodulin-dependent protein kinase kinases are AMP-activated protein kinase kinases. J Biol Chem 2005; 280: 29060–29066. · DOI
  17. Woods A, Dickerson K, Heath R, Hong SP, Momcilovic M, Johnstone SR et al. Ca2+/calmodulin-dependent protein kinase kinase-beta acts upstream of AMP-activated protein kinase in mammalian cells. Cell Metab 2005; 2: 21–33. · DOI
  18. Fogarty S, Hawley SA, Green KA, Saner N, Mustard KJ, Hardie DG . Calmodulin-dependent protein kinase kinase-beta activates AMPK without forming a stable complex: synergistic effects of Ca2+ and AMP. Biochem J 2010; 426: 109–118. · DOI
  19. Colell A, Ricci JE, Tait S, Milasta S, Maurer U, Bouchier-Hayes L et al. GAPDH and autophagy preserve survival after apoptotic cytochrome c release in the absence of caspase activation. Cell 2007; 129: 983–997. · DOI · Paper page
  20. Kroemer G, Pouyssegur J . Tumor cell metabolism: cancer's Achilles' heel. Cancer Cell 2008; 13: 472–482. · DOI · Paper page
  21. Castellino RC, Durden DL . Mechanisms of disease: the PI3K-Akt-PTEN signaling node--an intercept point for the control of angiogenesis in brain tumors. Nat Clin Pract Neurol 2007; 3: 682–693. · DOI
  22. Fleming A, Noda T, Yoshimori T, Rubinsztein DC . Chemical modulators of autophagy as biological probes and potential therapeutics. Nat Chem Biol 2011; 7: 9–17. · DOI
  23. Wang S, Song P, Zou MH . AMP-activated protein kinase, stress responses and cardiovascular diseases. Clin Sci (Lond) 2012; 122: 555–573. · DOI
  24. Lamberts RR, Onderwater G, Hamdani N, Vreden MJ, Steenhuisen J, Eringa EC et al. Reactive oxygen species-induced stimulation of 5'AMP-activated protein kinase mediates sevoflurane-induced cardioprotection. Circulation 2009; 120: S10–S15. · DOI
  25. Shrivastava A, Kuzontkoski PM, Groopman JE, Prasad A . Cannabidiol induces programmed cell death in breast cancer cells by coordinating the cross-talk between apoptosis and autophagy. Mol Cancer Ther 2011; 10: 1161–1172. · DOI
  26. Murray J, Taylor SW, Zhang B, Ghosh SS, Capaldi RA . Oxidative damage to mitochondrial complex I due to peroxynitrite: identification of reactive tyrosines by mass spectrometry. J Biol Chem 2003; 278: 37223–37230. · DOI
  27. Colell A, Green DR, Ricci JE . Novel roles for GAPDH in cell death and carcinogenesis. Cell Death Differ 2009; 16: 1573–1581. · DOI
  28. Dando I, Fiorini C, Pozza ED, Padroni C, Costanzo C, Palmieri M et al. UCP2 inhibition triggers ROS-dependent nuclear translocation of GAPDH and autophagic cell death in pancreatic adenocarcinoma cells. Biochim Biophys Acta 2013; 1833: 672–679. · DOI
  29. Kwon HJ, Rhim JH, Jang IS, Kim GE, Park SC, Yeo EJ . Activation of AMP-activated protein kinase stimulates the nuclear localization of glyceraldehyde 3-phosphate dehydrogenase in human diploid fibroblasts. Exp Mol Med 2010; 42: 254–269. · DOI
  30. Hitosugi T, Kang S, Vander Heiden MG, Chung TW, Elf S, Lythgoe K et al. Tyrosine phosphorylation inhibits PKM2 to promote the Warburg effect and tumor growth. Sci Signal 2009; 2: ra73. · DOI · Paper page
  31. David CJ, Chen M, Assanah M, Canoll P, Manley JL . HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA splicing in cancer. Nature 2010; 463: 364–368. · DOI · Paper page
  32. Aquila S, Guido C, Santoro A, Perrotta I, Laezza C, Bifulco M et al. Human sperm anatomy: ultrastructural localization of the cannabinoid1 receptor and a potential role of anandamide in sperm survival and acrosome reaction. Anat Rec (Hoboken) 2010; 293: 298–309. · DOI
  33. D'Alessandro A, Gevi F, Zolla L . A robust high resolution reversed-phase HPLC strategy to investigate various metabolic species in different biological models. Mol Biosyst 2011; 7: 1024–1032. · DOI
  34. Sana TR, Waddell K, Fischer SM . A sample extraction and chromatographic strategy for increasing LC/MS detection coverage of the erythrocyte metabolome. J Chromatogr B Analyt Technol Biomed Life Sci 2008; 871: 314–321. · DOI
  35. Christofk HR, Vander Heiden MG, Wu N, Asara JM, Cantley LC . Pyruvate kinase M2 is a phosphotyrosine-binding protein. Nature 2008; 452: 181–186. · DOI · Paper page

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Metadata

Authors
Dando, I., Donadelli, M., Costanzo, C., Dalla Pozza, E., D'Alessandro, A., Zolla, L., & Palmieri, M.
Venue
Cell Death & Disease
Publisher
Springer Science and Business Media LLC
Published
2013-06-13
Volume
4
Issue
6
Pages
e664-e664
ISSN
2041-4889
DOI
10.1038/cddis.2013.151
PMC
PMC3698539
Cited by
128
References
8
Language
en
Licence
www.springer.com/tdm (unspecified)

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Dando, I., Donadelli, M., Costanzo, C., Dalla Pozza, E., D'Alessandro, A., Zolla, L., & Palmieri, M. (2013). Cannabinoids inhibit energetic metabolism and induce AMPK-dependent autophagy in pancreatic cancer cells. Cell Death & Disease. https://doi.org/10.1038/cddis.2013.151