Sestrins As a Therapeutic Bridge Between ROS and Autophagy in Cancer

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2019 Sep 25

PMID 31546746

Citations 25

Authors

Miguel Sanchez-Alvarez

Raffaele Strippoli

Massimo Donadelli

Alexandr V Bazhin

Marco Cordani

Affiliations

Soon will be listed here.

Abstract

The regulation of Reactive Oxygen Species (ROS) levels and the contribution therein from networks regulating cell metabolism, such as autophagy and the mTOR-dependent nutrient-sensing pathway, constitute major targets for selective therapeutic intervention against several types of tumors, due to their extensive rewiring in cancer cells as compared to healthy cells. Here, we discuss the sestrin family of proteins-homeostatic transducers of oxidative stress, and drivers of antioxidant and metabolic adaptation-as emerging targets for pharmacological intervention. These adaptive regulators lie at the intersection of those two priority nodes of interest in antitumor intervention-ROS control and the regulation of cell metabolism and autophagy-therefore, they hold the potential not only for the development of completely novel compounds, but also for leveraging on synergistic strategies with current options for tumor therapy and classification/stadiation to achieve personalized medicine.

Citing Articles

Oxidative Stress and Autophagy: Unraveling the Hidden Threat to Boars' Fertility.

Hu R, Yang X, He J, Wu S Antioxidants (Basel). 2025; 14(1).

PMID: 39857336 PMC: 11761863. DOI: 10.3390/antiox14010002.

A Proteomic Approach Identified TFEB as a Key Player in the Protective Action of Novel CB2R Bitopic Ligand FD22a against the Deleterious Effects Induced by β-Amyloid in Glial Cells.

Polini B, Zallocco L, Gado F, Ferrisi R, Ricardi C, Zuccarini M Cells. 2024; 13(10.

PMID: 38786097 PMC: 11119469. DOI: 10.3390/cells13100875.

The oncogenic miR-429 promotes triple-negative breast cancer progression by degrading DLC1.

Li Y, Meng X, Luo Y, Luo S, Li J, Zeng J Aging (Albany NY). 2023; 15(18):9809-9821.

PMID: 37737712 PMC: 10564445. DOI: 10.18632/aging.205051.

Role of sestrins in metabolic and aging-related diseases.

Fang H, Shi X, Wan J, Zhong X Biogerontology. 2023; 25(1):9-22.

PMID: 37516672 DOI: 10.1007/s10522-023-10053-y.

Advanced Delivery System of Polyphenols for Effective Cancer Prevention and Therapy.

Kim K, Ki M, Min K, Pack S Antioxidants (Basel). 2023; 12(5).

PMID: 37237914 PMC: 10215831. DOI: 10.3390/antiox12051048.

References

Cordani M, Butera G, Dando I, Torrens-Mas M, Butturini E, Pacchiana R . Mutant p53 blocks SESN1/AMPK/PGC-1α/UCP2 axis increasing mitochondrial O· production in cancer cells. Br J Cancer. 2018; 119(8):994-1008. PMC: 6203762. DOI: 10.1038/s41416-018-0288-2. View

Kumari S, Badana A, G M, G S, Malla R . Reactive Oxygen Species: A Key Constituent in Cancer Survival. Biomark Insights. 2018; 13:1177271918755391. PMC: 5808965. DOI: 10.1177/1177271918755391. View

Singh S, Vats S, Chia A, Tan T, Deng S, Ong M . Dual role of autophagy in hallmarks of cancer. Oncogene. 2017; 37(9):1142-1158. DOI: 10.1038/s41388-017-0046-6. View

Lee J, Budanov A, Karin M . Sestrins orchestrate cellular metabolism to attenuate aging. Cell Metab. 2013; 18(6):792-801. PMC: 3858445. DOI: 10.1016/j.cmet.2013.08.018. View

Sanli T, Linher-Melville K, Tsakiridis T, Singh G . Sestrin2 modulates AMPK subunit expression and its response to ionizing radiation in breast cancer cells. PLoS One. 2012; 7(2):e32035. PMC: 3282792. DOI: 10.1371/journal.pone.0032035. View

Lord C, Ashworth A . The DNA damage response and cancer therapy. Nature. 2012; 481(7381):287-94. DOI: 10.1038/nature10760. View

Lee Y, Park S, Kim Y, Lee W, Park O . AMP kinase/cyclooxygenase-2 pathway regulates proliferation and apoptosis of cancer cells treated with quercetin. Exp Mol Med. 2009; 41(3):201-7. PMC: 2679247. DOI: 10.3858/emm.2009.41.3.023. View

Vakana E, Arslan A, Szilard A, Altman J, Platanias L . Regulatory effects of sestrin 3 (SESN3) in BCR-ABL expressing cells. PLoS One. 2013; 8(11):e78780. PMC: 3832611. DOI: 10.1371/journal.pone.0078780. View

Hua X, Xu J, Deng X, Xu J, Li J, Zhu D . New compound ChlA-F induces autophagy-dependent anti-cancer effect via upregulating Sestrin-2 in human bladder cancer. Cancer Lett. 2018; 436:38-51. PMC: 6245652. DOI: 10.1016/j.canlet.2018.08.013. View

10.

Bar-Peled L, Chantranupong L, Cherniack A, Chen W, Ottina K, Grabiner B . A Tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1. Science. 2013; 340(6136):1100-6. PMC: 3728654. DOI: 10.1126/science.1232044. View

11.

Laplante M, Sabatini D . mTOR signaling in growth control and disease. Cell. 2012; 149(2):274-93. PMC: 3331679. DOI: 10.1016/j.cell.2012.03.017. View

12.

Saxton R, Knockenhauer K, Wolfson R, Chantranupong L, Pacold M, Wang T . Structural basis for leucine sensing by the Sestrin2-mTORC1 pathway. Science. 2015; 351(6268):53-8. PMC: 4698039. DOI: 10.1126/science.aad2087. View

13.

Yen J, Huang S, Huang H, Fong Y, Wu Y, Chiang J . HGK-sestrin 2 signaling-mediated autophagy contributes to antitumor efficacy of Tanshinone IIA in human osteosarcoma cells. Cell Death Dis. 2018; 9(10):1003. PMC: 6158215. DOI: 10.1038/s41419-018-1016-9. View

14.

Haritunians T, Gueller S, Zhang L, Badr R, Yin D, Xing H . Cucurbitacin B induces differentiation, cell cycle arrest, and actin cytoskeletal alterations in myeloid leukemia cells. Leuk Res. 2008; 32(9):1366-73. DOI: 10.1016/j.leukres.2008.01.019. View

15.

Zhou G, Wang J, Zhao M, Xie T, Tanaka N, Sano D . Gain-of-function mutant p53 promotes cell growth and cancer cell metabolism via inhibition of AMPK activation. Mol Cell. 2014; 54(6):960-974. PMC: 4067806. DOI: 10.1016/j.molcel.2014.04.024. View

16.

Yan M, Vemu B, Veenstra J, Petiwala S, Johnson J . Carnosol, a dietary diterpene from rosemary () activates Nrf2 leading to sestrin 2 induction in colon cells. Integr Mol Med. 2019; 5(4). PMC: 6453141. DOI: 10.15761/IMM.1000335. View

17.

Kim S, Su L, Oh Y, Kemp B, Hong W, Mao L . Alterations of PTEN/MMAC1, a candidate tumor suppressor gene, and its homologue, PTH2, in small cell lung cancer cell lines. Oncogene. 1998; 16(1):89-93. DOI: 10.1038/sj.onc.1201512. View

18.

Kumar S, Yedjou C, Tchounwou P . Arsenic trioxide induces oxidative stress, DNA damage, and mitochondrial pathway of apoptosis in human leukemia (HL-60) cells. J Exp Clin Cancer Res. 2014; 33:42. PMC: 4049373. DOI: 10.1186/1756-9966-33-42. View

19.

Ambrosio S, Sacca C, Amente S, Paladino S, Lania L, Majello B . Lysine-specific demethylase LSD1 regulates autophagy in neuroblastoma through SESN2-dependent pathway. Oncogene. 2017; 36(48):6701-6711. PMC: 5717079. DOI: 10.1038/onc.2017.267. View

20.

Gammoh N, Lam D, Puente C, Ganley I, Marks P, Jiang X . Role of autophagy in histone deacetylase inhibitor-induced apoptotic and nonapoptotic cell death. Proc Natl Acad Sci U S A. 2012; 109(17):6561-5. PMC: 3340088. DOI: 10.1073/pnas.1204429109. View