Glycerol-mediated lysosomal associated proteins as a novel anticancer theory in colon cancer cell line
Abstract
Background: Colon cancer begins in the large intestine (colon) and is aggressive due to late diagnosis, so there is a poor prognosis and higher mortality rates, as reported. Colon cancer has become a vital research area requiring more investigation of cellular signaling in its initiation and development. Aim: The study aimed to investigate the biological effects of Glycerol in cell proliferation and the possible regulation of cellular signaling by exogenous treatment of Glycerol in colon cancer cells compared with colon mucosal epithelial cells.
Materials and Methods: The influence of Glycerol on cell viability rate was monitored by inverted microscopy, and the number of living cells was assessed upon incubation with different concentrations of Glycerol. We further inspected the apoptotic rate of CaCo-2 cells by using Annexin-V staining by flow cytometry. Moreover, we achieved the expression profile of lysosomal-associated proteins, LAMP-1 and LAMP-2, in treated cells using qRT-PCR and flow cytometry. Finally, we monitored the released pro-inflammatory cytokines and anti-inflammatory in response to Glycerol treatment using ELISA assay.
Results: Our results showed that Glycerol treatment could prevent cancer cell proliferation without any detectable cytotoxic occurrence in the normal cells. Interestingly, we evidenced that Glycerol targets and breaks down the lysosomal activities by inhibiting the expression profile of both LAMP-1 and LAMP-2. Furthermore, Glycerol treatment successfully adjusted the production of IL-6 and IL-8 as pro-inflammatory cytokines while stimulating the production of anti-inflammatory cytokines, IL-4 and IL-10, in a time-dependent manner.
Conclusion: These data provide evidence for the anti-cancer properties of Glycerol in colon cancer cells via targeting lysosomal activities and disturbance of the degradation events in colon cancer cells.
References
AIslam SMA, Patel R, Acevedo-Duncan M. Protein Kinase C-ζ stimulates colorectal cancer cell carcinogenesis via PKC-ζ/Rac1/Pak1/β-Catenin signaling cascade. Biochim Biophys Acta - Mol Cell Res 2018;1865:650–664.
Devenport SN, Shah YM. Functions and Implications of Autophagy in Colon Cancer. Cells 2019;8:1349.
Black AR, Black JD. Protein kinase C signaling and cell cycle regulation. Front Immunol 2013;3:423.
Abd El Maksoud AI, Elebeedy D, Abass NH, Awad AM, Nasr GM, et al. Methylomic Changes of Autophagy-
Related Genes by Legionella Effector Lpg2936 in Infected Macrophages. Front Cell Dev Biol 2020;7:390.
Abdelaziz DHA, Khalil H, Cormet-Boyaka E, Amer AO. The cooperation between the autophagy machinery and the inflammasome to implement an appropriate innate immune response: Do they regulate each other? Immunological Reviews 2015;265:194–204.
Burada F, Nicoli ER, Ciurea ME, Uscatu DC, Ioana M, et al. Autophagy in colorectal cancer: An important switch from physiology to pathology. World J Gastrointest Oncol 2015;7:271–284.
Khalil H, Tazi M, Caution K, Ahmed A, Kanneganti A, et al. Aging is associated with hypermethylation of autophagy genes in macrophages. Epigenetics 2016;11:381–388.
Khalil H, Abd El Maksoud AI, Alian A, El-Hamady WA, Daif AA, et al. Interruption of Autophagosome Formation in Cardiovascular Disease, an Evidence for Protective Response of Autophagy. Immunol Invest 2019;1–15.
Khalil H, El Malah T, El Maksoud AIA, El Halfawy I, El Rashedy AA, et al. Identification of novel and efficacious chemical compounds that disturb influenza A virus entry in vitro. Front Cell Infect Microbiol. Epub ahead of print 2017. DOI: 10.3389/fcimb.2017.00304.
Abd El Maksoud AI, Taher RF, Gaara AH, Abdelrazik E, Keshk OS, et al. Selective Regulation of B-Raf Dependent K-Ras/Mitogen-Activated Protein by Natural Occurring Multi-kinase Inhibitors in Cancer Cells. Front Oncol 2019;9:1220.
Abd El Maksoud AI, Taher RF, Gaara AH, Abdelrazik E, Keshk OS, et al. Selective Regulation of B-Raf Dependent K-Ras/Mitogen-Activated Protein by Natural Occurring Multi-kinase Inhibitors in Cancer Cells. Front Oncol 2019;9:1220.
Taher RF, Al-Karmalawy AA, Abd El Maksoud AI, Khalil H, Hassan A, et al. Two new flavonoids and anticancer activity of Hymenosporum flavum: in vitro and molecular docking studies. J Herbmed Pharmacol 2021;10:443–458.
Khalil H, Arfa M, El-Masrey S, EL-Sherbini S, Abd-Elaziz A. Single nucleotide polymorphisms of interleukins associated with hepatitis C virus infection in Egypt. J Infect Dev Ctries 2017;11:261–268.
Khalil H, Abd El Maksoud AI, Alian A, El-Hamady WA, Daif AA, et al. Interruption of Autophagosome Formation in Cardiovascular Disease, an Evidence for Protective Response of Autophagy. Immunol Invest 2020;49:249–263.
Wang Q, Yao J, Jin Q, Wang X, Zhu H, et al. LAMP1 expression is associated with poor prognosis in breast cancer. Oncol Lett 2017;14:4729–4735.
Kiffin R, Kaushik S, Zeng M, Bandyopadhyay U, Zhang C, et al. Altered dynamics of the lysosomal receptor for chaperone-mediated autophagy with age. J Cell Sci 2007;120:782–791.
Khalil H, Abd El Maksoud AI, Roshdey T, El-Masry S. Guava flavonoid glycosides prevent influenza A virus infection via rescue of P53 activity. J Med Virol 2019;91:45–55.
El-Fadl HMA, Hagag NM, El-Shafei RA, Khayri MH, El-Gedawy G, et al. Effective Targeting of Raf-1 and Its Associated Autophagy by Novel Extracted Peptide for Treating Breast Cancer Cells. Front Oncol 2021;11:3317.
Rao X, Huang X, Zhou Z, Lin X. An improvement of the2–delta delta CT) method for quantitative real-time polymerase chain reaction data analysis. Biostat Bioinforma Biomath. Epub ahead of print 2013. DOI: 10.1016/j.micinf.2011.07.011.Innate.
Wernke MJ. Glycerol. In: Wexler PBT-E of T (Third E (editor). Oxford: Academic Press. pp. 754–756.
Fekry T, Salem MF, Abd-Elaziz AA, Muawia S, Naguib YM, et al. Anticancer Properties of Selenium-Enriched Oyster Culinary-Medicinal Mushroom, Pleurotus ostreatus (Agaricomycetes), in Colon Cancer In Vitro. Int J Med Mushrooms 2022;24:1–20.
Mohamed E-SA, Bassiouny K, Alshambky AA, Khalil H. Anticancer Properties of N,N-dibenzylasparagine as an Asparagine (Asp) analog, Using Colon Cancer Caco-2 Cell Line. Asian Pacific J Cancer Prev 2022;23:2531–2540.
Hamouda RA, Abd El Maksoud AI, Wageed M, Alotaibi AS, Elebeedy D, et al. Characterization and Anticancer Activity of Biosynthesized Au/Cellulose Nanocomposite from Chlorella vulgaris. Polymers (Basel);13. Epub ahead of print 2021. DOI: 10.3390/polym13193340.
Liemann S, Lewit-Bentley A. Annexins: a novel family of calcium- and membrane-binding proteins in search of a function. Structure 1995;3:233–237.
Demchenko AP. Beyond annexin V: fluorescence response of cellular membranes to apoptosis. Cytotechnology 2013;65:157–172.
Ohnishi K, Ota I, Yane K, Takahashi A, Yuki K, et al. Glycerol as a chemical chaperone enhances radiation-induced apoptosis in anaplastic thyroid carcinoma cells. Mol Cancer 2002;1:4.
Tazi MF, Dakhlallah DA, Caution K, Gerber MM, Chang SW, et al. Elevated Mirc1/Mir17-92 cluster expression negatively regulates autophagy and CFTR (cystic fibrosis transmembrane conductance regulator) function in CF macrophages. Autophagy. Epub ahead of print 2016. DOI: 10.1080/15548627.2016.1217370.
Khalil H, Maksoud AIA El, Roshdey T, El‐Masry S. Guava flavonoid glycosides prevent influenza A virus infection via rescue of P53 activity. J Med Virol. Epub ahead of print 2018. DOI: 10.1002/jmv.25295.
Caution K, Gavrilin MA, Tazi M, Kanneganti A, Layman D, et al. Caspase-11 and caspase-1 differentially modulate actin polymerization via RhoA and Slingshot proteins to promote bacterial clearance. Sci Rep 2015;5:18479.
Abdulrahman BA, Khweek AA, Akhter A, Caution K, Kotrange S, et al. Autophagy stimulation by rapamycin suppresses lung inflammation and infection by Burkholderia cenocepacia in a model of cystic fibrosis. Autophagy. Epub ahead of print 2011. DOI: 10.4161/auto.7.11.17660.
Khalil H, Abd ElHady A, Elawdan KA, Mohamed D, Mohamed DD, et al. The Mechanical Autophagy as a Part of Cellular Immunity; Facts and Features in Treating the Medical Disorders. Immunol Invest 2022;51:266–289.
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