ISSN: 2423-6241
Continuous Volume
Vol. 7 (2021)
Adjunct Autophagy Suppression May Be a Promising Way to Eliminate the Resistance of Cancer Cells to Treatment Autophagy saves the cancer cells
Archives of Medical Laboratory Sciences,
Vol. 7 (2021),
,
Page 1-11 (e24)
https://doi.org/10.22037/amls.v7.35678
Abstract
Background and Aim: Autophagy is a highly conserved mechanism in eukaryotic cells which removes the dysfunctional organelles from the cell. Autophagy has immense physiological and pathological roles in cells. There are a variety of reports showing the dual function of autophagy as a tumor suppression and promotion phenomenon. Therefore, targeted therapy approaches like virotherapy can be a promising cancer treatment. Vesicular stomatitis virus (VSV) is a well-known oncolytic virus which mutations in its matrix (M) protein including M51R, make it a better candidate for oncotargeting. Moreover, beclin-1 is one of the key regulators of autophagy and also apoptosis.
Methods: In the present study, the level of autophagy markers such as beclin-1 and LC3 were investigated concerning the apoptosis process induction by VSV M-protein. Two colorectal cancer cell lines HCT116 and SW480 and one normal colon epithelial cell line (FHC) which expressing VSV M51R mutant M-protein were compared regarding autophagy versus apoptosis. All experiments were conducted at least in triplicate.
Results: The results showed that the elevated level of caspase 3 and reduced amount of beclin-1 in transfected SW480 cells may be an acceptable description for apoptosis.
Conclusion: In HCT116 cells domination of autophagy, plays a supportive mechanism for the cells to survive in response to M51R M-protein stress. Suppression of autophagy as an adjunct can be a promising way to eliminate resistance to cancer treatment. We have quantitively evaluated the Beclin-1 and LC3-II as autophagy markers, Future evaluation of these two along with other markers like P62 will reduce the limitations of this study.
*Corresponding Authors:
Dr. Mohamad Reza Kalani; Email: kalani@goums.ac.ir; ORCID: https://orcid.org/0000-0002-8756-1200
Dr. Abdolvahab Moradi; Email: dr.moradi@goums.ac.ir; ORCID: https://orcid.org/0000-0003-2877-4190
Please cite this article as: Mamizadeh Z, Kalani MR, Parsania M, Soltan Dallal MM, Moradi A. Adjunct Autophagy Suppression May Be a Promising Way to Eliminate the Resistance of Cancer Cells to Treatment. Arch Med Lab Sci. 2021;7:1-11 (e24). https://doi.org/10.22037/amls.v7.35678
- Apoptosis
- Autophagy
- Colorectal Cancer
- M-protein
- Oncolytic Virus
- VSV
How to Cite
References
Klionsky DJ. Autophagy revisited: A conversation with Christian de Duve. Autophagy. 2008 Aug 16;4(6):740–3.
Mizushima N, Komatsu M. Autophagy: Renovation of Cells and Tissues. Cell. 2011 Nov;147(4):728–41.
Lieberman OJ, Sulzer D. The Synaptic Autophagy Cycle. Journal of Molecular Biology. 2020 Apr;432(8):2589–604.
Mizushima N. Autophagy: process and function. Genes & Development. 2007 Nov 15;21(22):2861–73.
White E. Deconvoluting the context-dependent role for autophagy in cancer. Nat Rev Cancer. 2012 Jun;12(6):401–10.
Pleet ML, Branscome H, DeMarino C, Pinto DO, Zadeh MA, Rodriguez M, et al. Autophagy, EVs, and Infections: A Perfect Question for a Perfect Time. Front Cell Infect Microbiol. 2018 Oct 18;8:362.
Eskelinen E-L, Saftig P. Autophagy: A lysosomal degradation pathway with a central role in health and disease. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 2009 Apr;1793(4):664–73.
Eisenberg-Lerner A, Bialik S, Simon H-U, Kimchi A. Life and death partners: apoptosis, autophagy and the cross-talk between them. Cell Death Differ. 2009 Jul;16(7):966–75.
Sun Y, Peng Z-L. Autophagy, Beclin 1, and Their Relation To Oncogenesis. Laboratory Medicine. 2008 May;39(5):287–90.
Wirawan E, Lippens S, Vanden Berghe T, Romagnoli A, Fimia GM, Piacentini M, et al. Beclin1: A role in membrane dynamics and beyond. Autophagy. 2012 Jan;8(1):6–17.
Burada F. Autophagy in colorectal cancer: An important switch from physiology to pathology. WJGO. 2015;7(11):271.
Fukuhara H, Ino Y, Todo T. Oncolytic virus therapy: A new era of cancer treatment at dawn. Cancer Sci. 2016 Oct;107(10):1373–9.
Hastie E, Grdzelishvili VZ. Vesicular stomatitis virus as a flexible platform for oncolytic virotherapy against cancer. Journal of General Virology. 2012 Dec 1;93(12):2529–45.
Demeke A, Tassew A. Current Advancements on the Significance of Oncolytic Viruses in the Treatment of Tumor Cells. J Veterinar Sci Technol [Internet]. 2016 [cited 2020 Jul 16];07(02). Available from: https://www.omicsonline.org/open-access/current-advancements-on-the-significance-of-oncolytic-viruses-in-the-treatment-of-tumor-cells-2157-7579-1000308.php?aid=70012
Orzechowska BU, Jędryka M, Zwolińska K, Matkowski R. VSV based virotherapy in ovarian cancer: the past, the present and …future? J Cancer. 2017;8(12):2369–83.
Liu Y-P, Steele MB, Suksanpaisan L, Federspiel MJ, Russell SJ, Peng KW, et al. Oncolytic measles and vesicular stomatitis virotherapy for endometrial cancer. Gynecologic Oncology. 2014 Jan;132(1):194–202.
Blackham AU, Northrup SA, Willingham M, D’Agostino RB, Lyles DS, Stewart JH. Variation in susceptibility of human malignant melanomas to oncolytic vesicular stomatitis virus. Surgery. 2013 Mar;153(3):333–43.
Blackham AU, Northrup SA, Willingham M, Sirintrapun J, Russell GB, Lyles DS, et al. Molecular determinants of susceptibility to oncolytic vesicular stomatitis virus in pancreatic adenocarcinoma. Journal of Surgical Research. 2014 Apr;187(2):412–26.
Shinozaki K, Ebert O, Woo SLC. Eradication of advanced hepatocellular carcinoma in rats via repeated hepatic arterial infusions of recombinant VSV. Hepatology. 2005 Jan;41(1):196–203.
Ahmed M, Cramer SD, Lyles DS. Sensitivity of prostate tumors to wild type and M protein mutant vesicular stomatitis viruses. Virology. 2004 Dec;330(1):34–49.
Stewart JH, Ahmed M, Northrup SA, Willingham M, Lyles DS. Vesicular stomatitis virus as a treatment for colorectal cancer. Cancer Gene Ther. 2011 Dec;18(12):837–49.
Cary ZD, Willingham MC, Lyles DS. Oncolytic Vesicular Stomatitis Virus Induces Apoptosis in U87 Glioblastoma Cells by a Type II Death Receptor Mechanism and Induces Cell Death and Tumor Clearance In Vivo. Journal of Virology. 2011 Jun 15;85(12):5708–17.
Wang S, Yang Y, Luo D, Zhai L, Bai Y, Wei W, et al. Bisphenol A increases TLR4-mediated inflammatory response by up-regulation of autophagy-related protein in lung of adolescent mice. Chemosphere. 2021 Apr;268:128837.
Olagnier D, Lababidi RR, Hadj SB, Sze A, Liu Y, Naidu SD, et al. Activation of Nrf2 Signaling Augments Vesicular Stomatitis Virus Oncolysis via Autophagy-Driven Suppression of Antiviral Immunity. Molecular Therapy. 2017 Aug;25(8):1900–16.
Shelly S, Lukinova N, Bambina S, Berman A, Cherry S. Autophagy Is an Essential Component of Drosophila Immunity against Vesicular Stomatitis Virus. Immunity. 2009 Apr;30(4):588–98.
Ahmed M, Mitchell LM, Puckett S, Brzoza-Lewis KL, Lyles DS, Hiltbold EM. Vesicular Stomatitis Virus M Protein Mutant Stimulates Maturation of Toll-Like Receptor 7 (TLR7)-Positive Dendritic Cells through TLR-Dependent and -Independent Mechanisms. JVI. 2009 Apr 1;83(7):2962–75.
Krautwald S, Ziegler E, Rölver L, Linkermann A, Keyser KA, Steen P, et al. Effective Blockage of Both the Extrinsic and Intrinsic Pathways of Apoptosis in Mice by TAT-crmA. J Biol Chem. 2010 Jun 25;285(26):19997–20005.
Liu L, Zhao W-M, Yang X-H, Sun Z-Q, Jin H-Z, Lei C, et al. Effect of inhibiting Beclin-1 expression on autophagy, proliferation and apoptosis in colorectal cancer. Oncology Letters. 2017 Oct;14(4):4319–24.
Glick D, Barth S, Macleod KF. Autophagy: cellular and molecular mechanisms. J Pathol. 2010 May;221(1):3–12.
Peracchio C, Alabiso O, Valente G, Isidoro C. Involvement of autophagy in ovarian cancer: a working hypothesis. J Ovarian Res. 2012;5(1):22.
Burada F. Autophagy in colorectal cancer: An important switch from physiology to pathology. WJGO. 2015;7(11):271.
Guo G-F. Autophagy-related proteins Beclin-1 and LC3 predict cetuximab efficacy in advanced colorectal cancer. WJG. 2011;17(43):4779.
Runwal G, Stamatakou E, Siddiqi FH, Puri C, Zhu Y, Rubinsztein DC. LC3-positive structures are prominent in autophagy-deficient cells. Sci Rep. 2019 Dec;9(1):10147.
Wirawan E, Lippens S, Vanden Berghe T, Romagnoli A, Fimia GM, Piacentini M, et al. Beclin1: A role in membrane dynamics and beyond. Autophagy. 2012 Jan;8(1):6–17.
McKnight NC, Yue Z. Beclin 1, an Essential Component and Master Regulator of PI3K-III in Health and Disease. Curr Pathobiol Rep. 2013 Dec;1(4):231–8.
Levine B, Kroemer G. Autophagy in the Pathogenesis of Disease. Cell. 2008 Jan;132(1):27–42.
Kenific CM, Thorburn A, Debnath J. Autophagy and metastasis: another double-edged sword. Current Opinion in Cell Biology. 2010 Apr;22(2):241–5.
Wang Y, Jiang K, Zhang Q, Meng S, Ding C. Autophagy in Negative-Strand RNA Virus Infection. Front Microbiol. 2018 Feb 13;9:206.
Schache P, Gürlevik E, Strüver N, Woller N, Malek N, Zender L, et al. VSV virotherapy improves chemotherapy by triggering apoptosis due to proteasomal degradation of Mcl-1. Gene Ther. 2009 Jul;16(7):849–61.
Cui L, Wang X, Zhao X, Kong C, Li Z, Liu Y, et al. The autophagy-related genes Beclin1 and LC3 in the prognosis of pancreatic cancer. Int J Clin Exp Pathol. 2019;12(8):2989–96.
Fujii S, Mitsunaga S, Yamazaki M, Hasebe T, Ishii G, Kojima M, et al. Autophagy is activated in pancreatic cancer cells and correlates with poor patient outcome. Cancer Science. 2008 Jul;???-???
Schmitz KJ, Ademi C, Bertram S, Schmid KW, Baba HA. Prognostic relevance of autophagy-related markers LC3, p62/sequestosome 1, Beclin-1 and ULK1 in colorectal cancer patients with respect to KRAS mutational status. World J Surg Onc. 2016 Dec;14(1):189.
Shen H, Yin L, Deng G, Guo C, Han Y, Li Y, et al. Knockdown of Beclin-1 impairs epithelial-mesenchymal transition of colon cancer cells. J Cell Biochem. 2018 Aug;119(8):7022–31.
Sato K, Tsuchihara K, Fujii S, Sugiyama M, Goya T, Atomi Y, et al. Autophagy Is Activated in Colorectal Cancer Cells and Contributes to the Tolerance to Nutrient Deprivation. Cancer Research. 2007 Oct 15;67(20):9677–84.
Zhang M-Y, Gou W-F, Zhao S, Mao X-Y, Zheng Z-H, Takano Y, et al. Beclin 1 Expression is Closely Linked to Colorectal Carcinogenesis and Distant Metastasis of Colorectal Carcinoma. IJMS. 2014 Aug 18;15(8):14372–85.
Marinković M, Šprung M, Buljubašić M, Novak I. Autophagy Modulation in Cancer: Current Knowledge on Action and Therapy. Oxidative Medicine and Cellular Longevity. 2018;2018:1–18.
Liu P-F, Hu Y-C, Kang B-H, Tseng Y-K, Wu P-C, Liang C-C, et al. Expression levels of cleaved caspase-3 and caspase-3 in tumorigenesis and prognosis of oral tongue squamous cell carcinoma. Coleman WB, editor. PLoS ONE. 2017 Jul 10;12(7):e0180620.
Wolf BB, Schuler M, Echeverri F, Green DR. Caspase-3 Is the Primary Activator of Apoptotic DNA Fragmentation via DNA Fragmentation Factor-45/Inhibitor of Caspase-activated DNase Inactivation. J Biol Chem. 1999 Oct 22;274(43):30651–6.
Qian H-R, Shi Z-Q, Zhu H-P, Gu L-H, Wang X-F, Yang Y. Interplay between apoptosis and autophagy in colorectal cancer. Oncotarget. 2017 Sep 22;8(37):62759–68.
Djavaheri-Mergny M, Maiuri MC, Kroemer G. Cross talk between apoptosis and autophagy by caspase-mediated cleavage of Beclin 1. Oncogene. 2010 Mar;29(12):1717–9.
Maiuri MC, Zalckvar E, Kimchi A, Kroemer G. Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol. 2007 Sep;8(9):741–52.
Li X, He S, Ma B. Autophagy and autophagy-related proteins in cancer. Mol Cancer. 2020 Dec;19(1):12.
Lauzier A, Normandeau-Guimond J, Vaillancourt-Lavigueur V, Boivin V, Charbonneau M, Rivard N, et al. Colorectal cancer cells respond differentially to autophagy inhibition in vivo. Sci Rep. 2019 Dec;9(1):11316.
Mouradov D, Sloggett C, Jorissen RN, Love CG, Li S, Burgess AW, et al. Colorectal Cancer Cell Lines Are Representative Models of the Main Molecular Subtypes of Primary Cancer. Cancer Research. 2014 Jun 15;74(12):3238–47.
Zhao H, Yang M, Zhao B. Beclin 1 and LC3 as predictive biomarkers for metastatic colorectal carcinoma. Oncotarget. 2017 Aug 29;8(35):59058–67.
Gaddy DF, Lyles DS. Vesicular stomatitis viruses expressing wild-type or mutant M proteins activate apoptosis through distinct pathways. Journal of virology. 2005;79(7):4170–9.
Kyrylkova K, Kyryachenko S, Leid M, Kioussi C. Detection of Apoptosis by TUNEL Assay. In: Kioussi C, editor. Odontogenesis [Internet]. Totowa, NJ: Humana Press; 2012 [cited 2020 Jul 16]. p. 41–7. (Methods in Molecular Biology; vol. 887). Available from: http://link.springer.com/10.1007/978-1-61779-860-3_5
Atale N, Gupta S, Yadav UCS, Rani V. Cell-death assessment by fluorescent and nonfluorescent cytosolic and nuclear staining techniques: FLUORESCENT AND NONFLUORESCENT DNA STAINING TECHNIQUES. Journal of Microscopy. 2014 Jul;255(1):7–19.
Huang X, Qi Q, Hua X, Li X, Zhang W, Sun H, et al. Beclin 1, an autophagy-related gene, augments apoptosis in U87 glioblastoma cells. Oncology Reports. 2014 Apr;31(4):1761–7.
Shintani M. Autophagy as a Therapeutic Target in Gastrointestinal Cancer. In: Ntuli TM, editor. Cell Death - Autophagy, Apoptosis and Necrosis [Internet]. InTech; 2015 [cited 2020 Jul 16]. Available from: http://www.intechopen.com/books/cell-death-autophagy-apoptosis-and-necrosis/autophagy-as-a-therapeutic-target-in-gastrointestinal-cancer
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