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Curcumin-Induced Autophagy Augments Its Antitumor Effect against A172 Human Glioblastoma Cells

  • Lee, Jong-Eun (Department of Bioscience and Biotechnology, Sejong University) ;
  • Yoon, Sung Sik (Department of Bioscience and Biotechnology, Sejong University) ;
  • Moon, Eun-Yi (Department of Bioscience and Biotechnology, Sejong University)
  • Received : 2019.06.30
  • Accepted : 2019.07.19
  • Published : 2019.09.01

Abstract

Glioblastoma is the most aggressive common brain tumor in adults. Curcumin, from Curcuma longa, is an effective antitumor agent. Although the same proteins control both autophagy and cell death, the molecular connections between them are complicated and autophagy may promote or inhibit cell death. We investigated whether curcumin affects autophagy, which regulates curcumin-mediated tumor cell death in A172 human glioblastoma cells. When A172 cells were incubated with $10{\mu}M$ curcumin, autophagy increased in a time-dependent manner. Curcumin-induced cell death was reduced by co-incubation with the autophagy inhibitors 3-methyladenine (3-MA), hydroxychloroquine (HCQ), and LY294002. Curcumin-induced cell death was also inhibited by co-incubation with rapamycin, an autophagy inducer. When cells were incubated under serum-deprived medium, LC3-II amount was increased but the basal level of cell viability was reduced, leading to the inhibition of curcumin-induced cell death. Cell death was decreased by inhibiting curcumin-induced autophagy using small interference RNA (siRNA) of Atg5 or Beclin1. Therefore, curcumin-mediated tumor cell death is promoted by curcumin-induced autophagy, but not by an increase in the basal level of autophagy in rapamycin-treated or serum-deprived conditions. This suggests that the antitumor effects of curcumin are influenced differently by curcumin-induced autophagy and the prerequisite basal level of autophagy in cancer cells.

Acknowledgement

Supported by : National Research Foundation (NRF)

References

  1. Abdul Rahim, S. A., Dirkse, A., Oudin, A., Schuster, A., Bohler, J., Barthelemy, V., Muller, A., Vallar, L., Janji, B., Golebiewska, A. and Niclou, S. P. (2017) Regulation of hypoxia-induced autophagy in glioblastoma involves ATG9A. Br. J. Cancer 117, 813-825. https://doi.org/10.1038/bjc.2017.263
  2. Ak, T. and Gulcin, I. (2008) Antioxidant and radical scavenging properties of curcumin. Chem. Biol. Interact. 174, 27-37. https://doi.org/10.1016/j.cbi.2008.05.003
  3. Anand, P., Thomas, S. G., Kunnumakkara, A. B., Sundaram, C., Harikumar, K. B., Sung, B., Tharakan, S. T., Misra, K., Priyadarsini, I. K., Rajasekharan, K. N. and Aggarwal, B. B. (2008) Biological activities of curcumin and its analogues (Congeners) made by man and Mother Nature. Biochem. Pharmacol. 76, 1590-1611. https://doi.org/10.1016/j.bcp.2008.08.008
  4. Arcella, A., Biagioni, F., Antonietta Oliva, M., Bucci, D., Frati, A., Esposito, V., Cantore, G., Giangaspero, F. and Fornai, F. (2013) Rapamycin inhibits the growth of glioblastoma. Brain Res. 1495, 37-51. https://doi.org/10.1016/j.brainres.2012.11.044
  5. Blommaart, E. F., Krause, U., Schellens, J. P., Vreeling-Sindelarova, H. and Meijer, A. J. (1997) The phosphatidylinositol 3-kinase inhibitors wortmannin and LY294002 inhibit autophagy in isolated rat hepatocytes. Eur. J. Biochem. 243, 240-246. https://doi.org/10.1111/j.1432-1033.1997.0240a.x
  6. Bressin, C., Bourgarel-Rey, V., Carre, M., Pourroy, B., Arango, D., Braguer, D. and Barra, Y. (2006) Decrease in c-Myc activity enhances cancer cell sensitivity to vinblastine. Anticancer Drugs 17, 181-187. https://doi.org/10.1097/00001813-200602000-00009
  7. Calvino, E., Tejedor, M. C., Sancho, P., Herraez, A. and Diez, J. C. (2015) JNK and NFkappaB dependence of apoptosis induced by vinblastine in human acute promyelocytic leukaemia cells. Cell Biochem. Funct. 33, 211-219. https://doi.org/10.1002/cbf.3105
  8. Cassel, M., de Paiva Camargo, M., Oliveira de Jesus, L. W. and Borella, M. I. (2017) Involution processes of follicular atresia and post-ovulatory complex in a characid fish ovary: a study of apoptosis and autophagy pathways. J. Mol. Histol. 48, 243-257. https://doi.org/10.1007/s10735-017-9723-6
  9. Codogno, P., Mehrpour, M. and Proikas-Cezanne, T. (2011) Canonical and non-canonical autophagy: variations on a common theme of self-eating? Nat. Rev. Mol. Cell Biol. 13, 7-12.
  10. Fan, M., Goodwin, M., Vu, T., Brantley-Finley, C., Gaarde, W. A. and Chambers, T. C. (2000) Vinblastine-induced phosphorylation of Bcl-2 and Bcl-XL is mediated by JNK and occurs in parallel with inactivation of the Raf-1/MEK/ERK cascade. J. Biol. Chem. 275, 29980-29985. https://doi.org/10.1074/jbc.M003776200
  11. Fu, H., Wang, C., Yang, D., Zhang, X., Wei, Z., Zhu, Z., Xu, J., Hu, Z., Zhang, Y., Wang, W., Yan, R. and Cai, Q. (2018) Curcumin regulates proliferation, autophagy and apoptosis in gastric cancer cells by affecting PI3K and P53 signaling. J. Cell. Physiol. 233, 4634-4642. https://doi.org/10.1002/jcp.26190
  12. Giatromanolaki, A., Sivridis, E., Mitrakas, A., Kalamida, D., Zois, C. E., Haider, S., Piperidou, C., Pappa, A., Gatter, K. C., Harris, A. L. and Koukourakis, M. I. (2014) Autophagy and lysosomal related protein expression patterns in human glioblastoma. Cancer Biol. Ther. 15, 1468-1478. https://doi.org/10.4161/15384047.2014.955719
  13. Gupta, K. K., Bharne, S. S., Rathinasamy, K., Naik, N. R. and Panda, D. (2006) Dietary antioxidant curcumin inhibits microtubule assembly through tubulin binding. FEBS J. 273, 5320-5332. https://doi.org/10.1111/j.1742-4658.2006.05525.x
  14. He, C. and Klionsky, D. J. (2009) Regulation mechanisms and signaling pathways of autophagy. Annu. Rev. Genet. 43, 67-93. https://doi.org/10.1146/annurev-genet-102808-114910
  15. Kawamori, T., Lubet, R., Steele, V. E., Kelloff, G. J., Kaskey, R. B., Rao, C. V. and Reddy, B. S. (1999) Chemopreventive effect of curcumin, a naturally occurring anti-inflammatory agent, during the promotion/progression stages of colon cancer. Cancer Res. 59, 597-601.
  16. Klinger, N. V. and Mittal, S. (2016) Therapeutic potential of curcumin for the treatment of brain tumors. Oxid. Med. Cell. Longev. 2016, 9324085.
  17. Kunnumakkara, A. B., Anand, P. and Aggarwal, B. B. (2008) Curcumin inhibits proliferation, invasion, angiogenesis and metastasis of different cancers through interaction with multiple cell signaling proteins. Cancer Lett. 269, 199-225. https://doi.org/10.1016/j.canlet.2008.03.009
  18. Lee, J. W., Park, S., Kim, S. Y., Um, S. H. and Moon, E. Y. (2016) Curcumin hampers the antitumor effect of vinblastine via the inhibition of microtubule dynamics and mitochondrial membrane potential in HeLa cervical cancer cells. Phytomedicine 23, 705-713. https://doi.org/10.1016/j.phymed.2016.03.011
  19. Lee, J. W., Ryu, Y. K., Ji, Y. H., Kang, J. H. and Moon, E. Y. (2015) Hypoxia/reoxygenation-experienced cancer cell migration and metastasis are regulated by Rap1- and Rac1-GTPase activation via the expression of thymosin beta-4. Oncotarget 6, 9820-9833. https://doi.org/10.18632/oncotarget.3218
  20. Lefranc, F. and Kiss, R. (2006) Autophagy, the Trojan horse to combat glioblastomas. Neurosurg. Focus 20, E7. https://doi.org/10.3171/foc.2006.20.4.4
  21. Li, W., Zhou, Y., Yang, J., Li, H., Zhang, H. and Zheng, P. (2017) Curcumin induces apoptotic cell death and protective autophagy in human gastric cancer cells. Oncol. Rep. 37, 3459-3466. https://doi.org/10.3892/or.2017.5637
  22. Marino, G., Niso-Santano, M., Baehrecke, E. H. and Kroemer, G. (2014) Self-consumption: the interplay of autophagy and apoptosis. Nat. Rev. Mol. Cell Biol. 15, 81-94. https://doi.org/10.1038/nrm3735
  23. Mauthe, M., Orhon, I., Rocchi, C., Zhou, X., Luhr, M., Hijlkema, K. J., Coppes, R. P., Engedal, N., Mari, M. and Reggiori, F. (2018) Chloroquine inhibits autophagic flux by decreasing autophagosomelysosome fusion. Autophagy 14, 1435-1455. https://doi.org/10.1080/15548627.2018.1474314
  24. Monastyrska, I., Rieter, E., Klionsky, D. J. and Reggiori, F. (2009) Multiple roles of the cytoskeleton in autophagy. Biol. Rev. Camb. Philos. Soc. 84, 431-448. https://doi.org/10.1111/j.1469-185X.2009.00082.x
  25. Noonan, J., Zarrer, J. and Murphy, B. M. (2016) Targeting autophagy in glioblastoma. Crit. Rev. Oncog. 21, 241-252. https://doi.org/10.1615/CritRevOncog.2016017008
  26. Ryu, Y. K., Lee, J. W. and Moon, E. Y. (2015) Thymosin beta-4, actin-sequestering protein regulates vascular endothelial growth factor expression via hypoxia-inducible nitric oxide production in HeLa cervical cancer cells. Biomol. Ther. (Seoul) 23, 19-25. https://doi.org/10.4062/biomolther.2014.101
  27. Sa, G. and Das, T. (2008) Anti cancer effects of curcumin: cycle of life and death. Cell Div. 3, 14. https://doi.org/10.1186/1747-1028-3-14
  28. Sharma, K., Le, N., Alotaibi, M. and Gewirtz, D. A. (2014) Cytotoxic autophagy in cancer therapy. Int. J. Mol. Sci. 15, 10034-10051. https://doi.org/10.3390/ijms150610034
  29. Shehzad, A., Wahid, F. and Lee, Y. S. (2010) Curcumin in cancer chemoprevention: molecular targets, pharmacokinetics, bioavailability, and clinical trials. Arch. Pharm. (Weinheim) 343, 489-499. https://doi.org/10.1002/ardp.200900319
  30. Stadheim, T. A., Xiao, H. and Eastman, A. (2001) Inhibition of extracellular signal-regulated kinase (ERK) mediates cell cycle phase independent apoptosis in vinblastine-treated ML-1 cells. Cancer Res. 61, 1533-1540.
  31. Tashiro, E., Simizu, S., Takada, M., Umezawa, K. and Imoto, M. (1998) Caspase-3 activation is not responsible for vinblastine-induced Bcl-2 phosphorylation and G2/M arrest in human small cell lung carcinoma Ms-1 cells. Jpn. J. Cancer Res. 89, 940-946. https://doi.org/10.1111/j.1349-7006.1998.tb00652.x
  32. Tykocki, T. and Eltayeb, M. (2018) Ten-year survival in glioblastoma. A systematic review. J. Clin. Neurosci. 54, 7-13. https://doi.org/10.1016/j.jocn.2018.05.002
  33. Veeran, S., Shu, B., Cui, G., Fu, S. and Zhong, G. (2017) Curcumin induces autophagic cell death in Spodoptera frugiperda cells. Pestic. Biochem. Physiol. 139, 79-86. https://doi.org/10.1016/j.pestbp.2017.05.004
  34. Wilken, R., Veena, M. S., Wang, M. B. and Srivatsan, E. S. (2011) Curcumin: A review of anti-cancer properties and therapeutic activity in head and neck squamous cell carcinoma. Mol. Cancer 10, 12. https://doi.org/10.1186/1476-4598-10-12
  35. Wu, M., Lao, Y., Xu, N., Wang, X., Tan, H., Fu, W., Lin, Z. and Xu, H. (2015) Guttiferone K induces autophagy and sensitizes cancer cells to nutrient stress-induced cell death. Phytomedicine 22, 902-910. https://doi.org/10.1016/j.phymed.2015.06.008
  36. Wu, Y. T., Tan, H. L., Shui, G., Bauvy, C., Huang, Q., Wenk, M. R., Ong, C. N., Codogno, P. and Shen, H. M. (2010) Dual role of 3-methyladenine in modulation of autophagy via different temporal patterns of inhibition on class I and III phosphoinositide 3-kinase. J. Biol. Chem. 285, 10850-10861. https://doi.org/10.1074/jbc.M109.080796
  37. Yang, D. H., Lee, J. W., Lee, J. and Moon, E. Y. (2014) Dynamic rearrangement of F-actin is required to maintain the antitumor effect of trichostatin A. PLoS ONE 9, e97352. https://doi.org/10.1371/journal.pone.0097352
  38. Yao, C. W., Kang, K. A., Piao, M. J., Ryu, Y. S., Fernando, P., Oh, M. C., Park, J. E., Shilnikova, K., Na, S. Y., Jeong, S. U., Boo, S. J. and Hyun, J. W. (2017) Reduced autophagy in 5-fluorouracil resistant colon cancer cells. Biomol. Ther. (Seoul) 25, 315-320. https://doi.org/10.4062/biomolther.2016.069
  39. Yonekawa, T. and Thorburn, A. (2013) Autophagy and cell death. Essays Biochem. 55, 105-117. https://doi.org/10.1042/bse0550105
  40. Zanotto-Filho, A., Braganhol, E., Klafke, K., Figueiro, F., Terra, S. R., Paludo, F. J., Morrone, M., Bristot, I. J., Battastini, A. M., Forcelini, C. M., Bishop, A. J., Gelain, D. P. and Moreira, J. C. (2015) Autophagy inhibition improves the efficacy of curcumin/temozolomide combination therapy in glioblastomas. Cancer Lett. 358, 220-231. https://doi.org/10.1016/j.canlet.2014.12.044
  41. Zhang, J., Wang, J., Xu, J., Lu, Y., Jiang, J., Wang, L., Shen, H. M. and Xia, D. (2016) Curcumin targets the TFEB-lysosome pathway for induction of autophagy. Oncotarget 7, 75659-75671. https://doi.org/10.18632/oncotarget.12318