Resveratrol-induced Autophagy in Human U373 Glioma Cells

Overview

Journal Oncol Lett

Specialty Oncology

Date 2012 Sep 12

PMID 22966330

Citations 15

Authors

Midori Yamamoto

Satoshi O Suzuki

Masaru Himeno

Affiliations

Soon will be listed here.

Abstract

Autophagy is an intracellular protein transport process leading to the degradation of organelles and long-lived proteins in eukaryotes. The down-regulation of autophagy observed in cancer cells has been associated with tumor progression. This study investigated autophagy induced by resveratrol, a natural compound, in human glioma cells. Glioma cells were exposed to resveratrol, and the cell growth and autophagic level were evaluated. Resveratrol inhibited growth and induced cell death in U373 glioma cells. When treated with resveratrol, glioma cells stably expressing GFP fused to LC3, recruited more GFP-LC3-labeled autophagosomes, and the percentage of cells with GFP-LC3-labeled autophagosomes increased. Furthermore, in resveratrol-treated glioma cells, pretreatment with P38 or ERK1/2 inhibitors reduced the autophagic level, suggesting that resveratrol-induced autophagy was positively regulated by P38 and the ERK1/2 pathway. The Akt/mTOR pathway was not involved in resveratrol-induced autophagy. Our results suggest that resveratrol has an anticancer effect on glioma cells by inducing autophagy.

Citing Articles

The Small Molecules of Plant Origin with Anti-Glioma Activity.

Liu X, Su Y, Yang Y, Li R, Zhang Z Int J Mol Sci. 2025; 26(5).

PMID: 40076568 PMC: 11900624. DOI: 10.3390/ijms26051942.

Proanthocyanidin Regulates NETosis and Inhibits the Growth and Proliferation of Liver Cancer Cells - In Vivo, In Vitro and In Silico Investigation.

Wang C, Xia W Cell Biochem Biophys. 2024; 83(1):1223-1235.

PMID: 39382828 DOI: 10.1007/s12013-024-01557-6.

The 3,3'-dimethoxy-4,4'-dihydroxy-stilbene Triazole (STT) Inhibits Liver Cancer Cell Growth by Targeting Akt/mTOR Pathway.

Sun M, Bai J, Wang H, Zhou L, Li S Dokl Biochem Biophys. 2024; 517(1):277-284.

PMID: 39002015 DOI: 10.1134/S1607672923600537.

Inhibition of Liver Cancer Cell Viability by Triazole through Up-regulation of p38 Phosphorylation and Targeting the Activation of p-ERK1/2 and Akt Protein Expression.

Li S, Zhou L, Zhao F, Wang H, Sun M Dokl Biochem Biophys. 2024; 516(1):66-72.

PMID: 38700817 DOI: 10.1134/S1607672923600525.

New Visions on Natural Products and Cancer Therapy: Autophagy and Related Regulatory Pathways.

Martelli A, Omrani M, Zarghooni M, Citi V, Brogi S, Calderone V Cancers (Basel). 2022; 14(23).

PMID: 36497321 PMC: 9738256. DOI: 10.3390/cancers14235839.

References

MAHALEY Jr M, Mettlin C, Natarajan N, Laws Jr E, Peace B . National survey of patterns of care for brain-tumor patients. J Neurosurg. 1989; 71(6):826-36. DOI: 10.3171/jns.1989.71.6.0826. View

Yang C, Landau J, Huang M, Newmark H . Inhibition of carcinogenesis by dietary polyphenolic compounds. Annu Rev Nutr. 2001; 21:381-406. DOI: 10.1146/annurev.nutr.21.1.381. View

Joe A, Liu H, Suzui M, Vural M, Xiao D, Weinstein I . Resveratrol induces growth inhibition, S-phase arrest, apoptosis, and changes in biomarker expression in several human cancer cell lines. Clin Cancer Res. 2002; 8(3):893-903. View

Fauconneau B, Waffo-Teguo P, Huguet F, Barrier L, Decendit A, Merillon J . Comparative study of radical scavenger and antioxidant properties of phenolic compounds from Vitis vinifera cell cultures using in vitro tests. Life Sci. 1997; 61(21):2103-10. DOI: 10.1016/s0024-3205(97)00883-7. View

Meijer A, Codogno P . Regulation and role of autophagy in mammalian cells. Int J Biochem Cell Biol. 2004; 36(12):2445-62. DOI: 10.1016/j.biocel.2004.02.002. View

Aoki H, Takada Y, Kondo S, Sawaya R, Aggarwal B, Kondo Y . Evidence that curcumin suppresses the growth of malignant gliomas in vitro and in vivo through induction of autophagy: role of Akt and extracellular signal-regulated kinase signaling pathways. Mol Pharmacol. 2007; 72(1):29-39. DOI: 10.1124/mol.106.033167. View

Botti J, Djavaheri-Mergny M, Pilatte Y, Codogno P . Autophagy signaling and the cogwheels of cancer. Autophagy. 2006; 2(2):67-73. DOI: 10.4161/auto.2.2.2458. View

Ellington A, Berhow M, Singletary K . Induction of macroautophagy in human colon cancer cells by soybean B-group triterpenoid saponins. Carcinogenesis. 2004; 26(1):159-67. DOI: 10.1093/carcin/bgh297. View

Santana P, Pena L, Haimovitz-Friedman A, Martin S, Green D, McLoughlin M . Acid sphingomyelinase-deficient human lymphoblasts and mice are defective in radiation-induced apoptosis. Cell. 1996; 86(2):189-99. DOI: 10.1016/s0092-8674(00)80091-4. View

10.

Kanzawa T, Germano I, Komata T, Ito H, Kondo Y, Kondo S . Role of autophagy in temozolomide-induced cytotoxicity for malignant glioma cells. Cell Death Differ. 2004; 11(4):448-57. DOI: 10.1038/sj.cdd.4401359. View

11.

Rubinsztein D, Gestwicki J, Murphy L, Klionsky D . Potential therapeutic applications of autophagy. Nat Rev Drug Discov. 2007; 6(4):304-12. DOI: 10.1038/nrd2272. View

12.

Gusman J, Malonne H, Atassi G . A reappraisal of the potential chemopreventive and chemotherapeutic properties of resveratrol. Carcinogenesis. 2001; 22(8):1111-7. DOI: 10.1093/carcin/22.8.1111. View

13.

Opipari Jr A, Tan L, Boitano A, Sorenson D, Aurora A, Liu J . Resveratrol-induced autophagocytosis in ovarian cancer cells. Cancer Res. 2004; 64(2):696-703. DOI: 10.1158/0008-5472.can-03-2404. View

14.

Ohgaki H, Dessen P, Jourde B, Horstmann S, Nishikawa T, Di Patre P . Genetic pathways to glioblastoma: a population-based study. Cancer Res. 2004; 64(19):6892-9. DOI: 10.1158/0008-5472.CAN-04-1337. View

15.

Simone C . Signal-dependent control of autophagy and cell death in colorectal cancer cell: the role of the p38 pathway. Autophagy. 2007; 3(5):468-71. DOI: 10.4161/auto.4319. View

16.

Maiuri M, Zalckvar E, Kimchi A, Kroemer G . Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol. 2007; 8(9):741-52. DOI: 10.1038/nrm2239. View

17.

Kanzawa T, Kondo Y, Ito H, Kondo S, Germano I . Induction of autophagic cell death in malignant glioma cells by arsenic trioxide. Cancer Res. 2003; 63(9):2103-8. View

18.

Jiang H, Zhang L, Kuo J, Kuo K, Gautam S, Groc L . Resveratrol-induced apoptotic death in human U251 glioma cells. Mol Cancer Ther. 2005; 4(4):554-61. DOI: 10.1158/1535-7163.MCT-04-0056. View

19.

Corcelle E, Djerbi N, Mari M, Nebout M, Fiorini C, Fenichel P . Control of the autophagy maturation step by the MAPK ERK and p38: lessons from environmental carcinogens. Autophagy. 2006; 3(1):57-9. DOI: 10.4161/auto.3424. View

20.

Knecht E, Hernandez-Yago J, Grisolia S . Regulation of lysosomal autophagy in transformed and non-transformed mouse fibroblasts under several growth conditions. Exp Cell Res. 1984; 154(1):224-32. DOI: 10.1016/0014-4827(84)90682-7. View