Ethoxyquin Inhibits the Progression of Murine Ehrlich Ascites Carcinoma through the Inhibition of Autophagy and LDH

Journal article


Tayel, Fekria, Mahfouz, Magdy E., Salama, Afrah F. and Mansour, M. (2021). Ethoxyquin Inhibits the Progression of Murine Ehrlich Ascites Carcinoma through the Inhibition of Autophagy and LDH. Biomedicines. 9 (11), p. e1526. https://doi.org/10.3390/biomedicines9111526
AuthorsTayel, Fekria, Mahfouz, Magdy E., Salama, Afrah F. and Mansour, M.
AbstractCancer cells exhibit an increased glycolysis rate for ATP generation (the Warburg effect) to sustain an increased proliferation rate. In tumor cells, the oxidation of pyruvate in the Krebs cycle is substituted by lactate production, catalyzed by LDH. In this study, we use ethoxyquin (EQ) as a novel inhibitor to target LDH in murine Ehrlich ascites carcinoma (EAC) and as a combination therapy to improve the therapeutic efficacy of the conventional chemotherapy drug, cisplatin (CIS). We investigated the anti-tumor effect of EQ on EAC-bearing mice and checked whether EQ can sustain the anti-tumor potential of CIS and whether it influences LDH activity. Treatment with EQ had evident anti-tumor effects on EAC as revealed by the remarkable decrease in the expression of the anti-apoptotic gene Bcl-2 and by a significant increase in the expression of apoptotic genes (BAX and caspase-3). EQ also caused a significant decrease in the autophagic activity of EAC cells, as shown by a reduction in the fluorescence intensity of the autophagosome marker. Additionally, EQ restored the altered hematological and biochemical parameters and improved the disrupted hepatic tissues of EAC-bearing mice. Co-administration of EQ and CIS showed the highest anti-tumor effect against EAC. Collectively, our findings propose EQ as a novel inhibitor of LDH in cancer cells and as a combinatory drug to increase the efficacy of cisplatin. Further studies are required to validate this therapeutic strategy in different cancer models and preclinical trials.
Keywordsethoxyquin; LDH; glycolysis; autophagy; cisplatin; Ehrlich ascites carcinoma
Year2021
JournalBiomedicines
Journal citation9 (11), p. e1526
PublisherMDPI
ISSN2227-9059
Digital Object Identifier (DOI)https://doi.org/10.3390/biomedicines9111526
Funder/ClientAcademy of Scientific Research and Technology, Scientists of next generation grant.
Publication dates
Online23 Oct 2021
Publication process dates
Accepted22 Oct 2021
Deposited10 Nov 2021
Publisher's version
License
File Access Level
Open
Licensehttps://creativecommons.org/licenses/by/4.0/
Permalink -

https://openresearch.lsbu.ac.uk/item/8yq83

Download files


Publisher's version
biomedicines-09-01526-v2.pdf
License: CC BY 4.0
File access level: Open

  • 17
    total views
  • 0
    total downloads
  • 1
    views this month
  • 0
    downloads this month

Export as

Related outputs

Tioconazole and Chloroquine Act Synergistically to Combat Doxorubicin-Induced Toxicity via Inactivation of PI3K/AKT/mTOR Signaling Mediated ROS-Dependent Apoptosis and Autophagic Flux Inhibition in MCF-7 Breast Cancer Cells.
El-Gowily, A.H., Loutfy, S.A., Ali, E., Mohamed, T. and Mansour, M. (2021). Tioconazole and Chloroquine Act Synergistically to Combat Doxorubicin-Induced Toxicity via Inactivation of PI3K/AKT/mTOR Signaling Mediated ROS-Dependent Apoptosis and Autophagic Flux Inhibition in MCF-7 Breast Cancer Cells. Pharmaceuticals. 14 (3). https://doi.org/ph14030254
SP3 is associated with migration, invasion, and Akt/PKB signalling in MDA‐MB‐231 breast cancer cells
Mansour, M. (2020). SP3 is associated with migration, invasion, and Akt/PKB signalling in MDA‐MB‐231 breast cancer cells. Journal of biochemical and molecular toxicology. 35 (3). https://doi.org/10.1002/jbt.22657
Dual inhibition of glycolysis and autophagy as a therapeutic strategy in the treatment of Ehrlich ascites carcinoma
Mansour, MA, Ibrahim, WM, Salama, MM and Salama, AF (2020). Dual inhibition of glycolysis and autophagy as a therapeutic strategy in the treatment of Ehrlich ascites carcinoma. Journal of Biochemical and Molecular Toxicology. 34 (7). https://doi.org/10.1002/jbt.22498
Assessment of Autophagy as Possible Mechanism of the Antitumor Effects of Arsenic Trioxide and/or Cisplatin on Ehrlich Ascites Carcinoma Model.
Mansour, M.A., Salama, A.F., Ibrahim, W.M. and Shalaan, E.S. (2019). Assessment of Autophagy as Possible Mechanism of the Antitumor Effects of Arsenic Trioxide and/or Cisplatin on Ehrlich Ascites Carcinoma Model. Alexandria Journal for Veterinary Sciences. 61 (1), pp. 159-167. https://doi.org/10.5455/ajvs.29544
Combination of arsenic trioxide and cisplatin synergistically inhibits both hexokinase activity and viability of Ehrlich ascites carcinoma cells
Mansour, Mohammed A, Ibrahim, Wafaa M, Shalaan, Eman S and Salama, Afrah F (2019). Combination of arsenic trioxide and cisplatin synergistically inhibits both hexokinase activity and viability of Ehrlich ascites carcinoma cells. Journal of biochemical and molecular toxicology. 33, pp. e22350-e22350. https://doi.org/10.1002/jbt.22350
Cisplatin augments the anti-schistosomal effect of praziquantel in a schistosoma-infected cancer model
Salem, M.L., Salama, A., El-Gowily, A.H., Mansour, M.A. and El-Said, M.M.A. (2019). Cisplatin augments the anti-schistosomal effect of praziquantel in a schistosoma-infected cancer model. Indian Journal of Biochemistry and Biophysics (IJBB). 56, pp. 57-69.
Pd (II) and Pt (II) chalcone complexes. Synthesis, spectral characterization, molecular modeling, biomolecular docking, antimicrobial and antitumor activities
Gaber, M., El-Ghamry, H.A and Mansour, M.A. (2018). Pd (II) and Pt (II) chalcone complexes. Synthesis, spectral characterization, molecular modeling, biomolecular docking, antimicrobial and antitumor activities. Journal of Photochemistry and Photobiology A: Chemistry. 354, pp. 163-174. https://doi.org/10.1016/j.jphotochem.2017.07.031
Nano-synthesis, characterization, modeling and molecular docking analysis of Mn (II), Co (II), Cr (III) and Cu (II) complexes with azo pyrazolone ligand as new favorable antimicrobial and antitumor agents
Gaber, M., Khedr, A.M., Mansour, M.A. and Elsharkawy, M. (2018). Nano-synthesis, characterization, modeling and molecular docking analysis of Mn (II), Co (II), Cr (III) and Cu (II) complexes with azo pyrazolone ligand as new favorable antimicrobial and antitumor agents. Applied Organometallic Chemistry. 32, pp. e4606-e4606. https://doi.org/10.1002/aoc.4606
Synthesis, spectroscopic, thermal and molecular modeling studies of Zn2+, Cd2+ and UO22+ complexes of Schiff bases containing triazole moiety. Antimicrobial, anticancer, antioxidant and DNA binding studies
Gaber, M., El-Ghamry, H.A., Fathalla, S.K. and Mansour, M.A. (2018). Synthesis, spectroscopic, thermal and molecular modeling studies of Zn2+, Cd2+ and UO22+ complexes of Schiff bases containing triazole moiety. Antimicrobial, anticancer, antioxidant and DNA binding studies. Materials Science and Engineering: C. 83, pp. 78-89. https://doi.org/10.1016/j.msec.2017.11.004
The phospholipid PI (3, 4) P 2 is an apical identity determinant
Román-Fernández, Á., Roignot, J., Sandilands, E., Nacke, M., Mansour, M.A., McGarry, L., Shanks, E., Mostov, K.E. and Bryant, D.M. (2018). The phospholipid PI (3, 4) P 2 is an apical identity determinant. Nature Communications. 9, pp. 1-17. https://doi.org/10.1038/s41467-018-07464-8
Ubiquitination: Friend and foe in cancer
Mansour, M.A. (2018). Ubiquitination: Friend and foe in cancer. The international journal of biochemistry & cell biology. 101, pp. 80-93. https://doi.org/10.1016/j.biocel.2018.06.001
FAM98A associates with DDX1-C14orf166-FAM98B in a novel complex involved in colorectal cancer progression
Akter, K.A., Mansour, M.A., Hyodo, T. and Senga, T. (2017). FAM98A associates with DDX1-C14orf166-FAM98B in a novel complex involved in colorectal cancer progression. The international journal of biochemistry & cell biology. 84, pp. 1-13. https://doi.org/10.1016/j.biocel.2016.12.013
HOXD8 exerts a tumor-suppressing role in colorectal cancer as an apoptotic inducer
Mansour, M.A. and Senga, T. (2017). HOXD8 exerts a tumor-suppressing role in colorectal cancer as an apoptotic inducer. The international journal of biochemistry & cell biology. 88, pp. 1-13. https://doi.org/10.1016/j.biocel.2017.04.011
SATB1 and SATB2 play opposing roles in c-Myc expression and progression of colorectal cancer
Mansour, MA, Hyodo, T, Akter, KA, Kokuryo, T, Uehara, K, Nagino, M and Senga, T (2016). SATB1 and SATB2 play opposing roles in c-Myc expression and progression of colorectal cancer. Oncotarget. 7, pp. 4993-4993. https://doi.org/10.18632/oncotarget.6651
UBE2S is associated with malignant characteristics of breast cancer cells
Ayesha, A K, Hyodo, T, Asano, E, Sato, N, Mansour, M A, Ito, S, Hamaguchi, M and Senga, T (2016). UBE2S is associated with malignant characteristics of breast cancer cells. Tumor Biology. 37 (1), pp. 763-772. https://doi.org/10.1007/s13277-015-3863-7
FAM98A is a novel substrate of PRMT1 required for tumor cell migration, invasion, and colony formation
Akter, K.A., Mansour, M.A., Hyodo, T., Ito, S., Hamaguchi, M. and Senga, T. (2016). FAM98A is a novel substrate of PRMT1 required for tumor cell migration, invasion, and colony formation. Tumor Biology. 37, pp. 4531-4539. https://doi.org/10.1007/s13277-015-4310-5
TRIP13 is expressed in colorectal cancer and promotes cancer cell invasion
Kurita, K, Maeda, M, Mansour, MA, Kokuryo, T, Uehara, K, Yokoyama, Y, Nagino, M, Hamaguchi, M and Senga, T (2016). TRIP13 is expressed in colorectal cancer and promotes cancer cell invasion. Oncology letters. 12, pp. 5240-5246. https://doi.org/10.3892/ol.2016.5332
Special AT-rich sequence-binding protein 2 suppresses invadopodia formation in HCT116 cells via palladin inhibition
Mansour, M.A., Asano, E., Hyodo, T., Akter, K.A., Takahashi, M., Hamaguchi, M. and Senga, T. (2015). Special AT-rich sequence-binding protein 2 suppresses invadopodia formation in HCT116 cells via palladin inhibition. Experimental Cell Research. 332, pp. 78-88. https://doi.org/10.1016/j.yexcr.2014.12.003
SATB 2 suppresses the progression of colorectal cancer cells via inactivation of MEK 5/ERK 5 signaling
Mansour, M.A., Hyodo, T., Ito, S., Kurita, K., Kokuryo, T., Uehara, K., Nagino, M., Takahashi, M., Hamaguchi, M. and Senga, T. (2015). SATB 2 suppresses the progression of colorectal cancer cells via inactivation of MEK 5/ERK 5 signaling. The FEBS journal. 282 (8), pp. 1394-1405. https://doi.org/10.1111/febs.13227
Treatment with folic acid ameliorated the histopathological alterations caused by propylthiouracil-induced hypothyroid rat testes
Tousson, E., Ali, E.M.M., Ibrahim, W. and Mansour, M.A. (2012). Treatment with folic acid ameliorated the histopathological alterations caused by propylthiouracil-induced hypothyroid rat testes. Toxicology and industrial health. 28 (6), pp. 566-576. https://doi.org/10.1177/0748233711420469
Folic acid alleviates oxidative stress and hyperhomocysteinemia involved in testicular dysfunction of hypothyroid rats
Ibrahim, W., Tousson, E., Ali, E.M.M. and Mansour, M.A. (2011). Folic acid alleviates oxidative stress and hyperhomocysteinemia involved in testicular dysfunction of hypothyroid rats. General and comparative endocrinology. 174, pp. 143-149. https://doi.org/10.1016/j.ygcen.2011.08.012
Proliferating cell nuclear antigen as a molecular biomarker for spermatogenesis in PTU-induced hypothyroidism of rats
Tousson, E., Ali, E.M.M., Ibrahim, W. and Mansour, M.A. (2011). Proliferating cell nuclear antigen as a molecular biomarker for spermatogenesis in PTU-induced hypothyroidism of rats. Reproductive sciences. 18, pp. 679-686. https://doi.org/10.1177/1933719110395401