2-Deoxyglucose Glycolysis Inhibitor Augment Oncolytic Virotherapy to Induce Oxidative Stress and Apoptosis in Breast Cancer (Part Ⅲ)
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Abstract
One of the "hallmarks of cancer" is altered energy metabolism, which is increased glycolysis in cancer cells, the primary source of energy that uses this metabolic pathway to generate ATP. Oncolytic virotherapy with aerobic glycolysis inhibitor smart therapeutic approach to induce apoptosis in cancer cells. The current study aimed to use the 2-Deoxyglucose (2DG), a specific glycolysis inhibitor, to enhance the Newcastle disease virus (NDV). In this study, a mouse model of breast cancer allograft with mammary adenocarcinoma tumor cells (AN3) was used and treated with 2DG, NDV, and a combination of both. Anti-tumor efficacy and glycolysis analysis (hexokinase -1 (HK-1), pyruvate, and ATP) were determined. The induction of oxidative stress was investigated by reactive oxygen species (ROS) and total glutathione assay examination. Apoptosis induction was investigated using immunohistochemistry (cleaved Caspase-3) and histopathology. The result showed that combination therapy enhances anti-tumor efficacy (decrease in relative tumor volume and increase in tumor growth inhibition) of NDV against breast cancer. This effect was accompanied by a reduction in HK-1 concentration, pyruvate, and ATP (glycolysis products). Moreover, NDV+2DG therapy induces oxidative stress (decreases total glutathione and increases ROS). Immunohistochemistry and histopathological examination showed the apoptotic area in tumor tissues in treated groups. In conclusion, the present study found that the combination therapy could be considered as an effective cancer therapy through induction of glycolysis inhibition, oxidative stress, and apoptosis selectively in cancer cells.
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Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000; 100(1): 57-70.
Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011; 144(5): 646-674.
Aft RL, Zhang F, Gius D. Evaluation of 2-deoxy-D-glucose as a chemotherapeutic agent: mechanism of cell death. Br. J. Cancer. 2002; 87(7): 805-812.
Pajak B, Siwiak E, Soltyka M, Priebe A, Zielinski R, Fokt I, et al. 2-Deoxy-d-glucose and its analogs: from diagnostic to therapeutic agents. Int. J. Mol. Sci. 2020; 21(1): 234.
Wang Q, Liang B, Shirwany NA, Zou MH. 2-Deoxy-D-glucose treatment of endothelial cells induces autophagy by reactive oxygen species-mediated activation of the AMP-activated protein kinase. PLoS One. 2011; 6(2): e17234.
Zhang D, Fei Q, Li J, Zhang C, Sun Y, Zhu C, et al. 2-Deoxyglucose reverses the promoting effect of insulin on colorectal cancer cells in vitro. PLoS One. 2016; 11(3): e0151115.
Simons AL, Mattson DM, Dornfeld K, Spitz DR. Glucose deprivation-induced metabolic oxidative stress and cancer therapy. J. Cancer Res. Ther. 2009; 5 Suppl 1: S2-6.
Zhao Y, Butler EB, Tan M. Targeting cellular metabolism to improve cancer therapeutics. Cell Death Dis. 2013; 4(3): e532-e.
Keenan J, Liang Y, Clynes M. Two-deoxyglucose as an anti-metabolite in human carcinoma cell line RPMI-2650 and drug-resistant variants. Anticancer Res. 2004; 24(2a): 433-440.
AL-bana AS, Allawe AB, Sebbar AA, Isolation & identification of Newcastle disease virus from wild pigeons. Iraqi J. Vet. Med. 2007; 31(2): 133-140.
Al-Shamery A, Yaseen N, Alwan M. Study the antigenic modification of tumor cell surface by NDV infection. Iraqi J Cancer Med Genet. 2009; 2(1):95-100.
Al-Shammari AM, Humadi TJ, Al-Taee EH, Al-Atabi SM, Yaseen NY. 439. Oncolytic Newcastle disease virus Iraqi virulent strain induce apoptosis in vitro through intrinsic pathway and association of both intrinsic and extrinsic pathways in vivo. Mol Ther. 2015; 23(S1): S173-S174.
Al-Shammary AM, Hassani HH, Ibrahim UAJ. Newcastle disease virus (NDV) Iraqi strain AD2141 induces DNA damage and FasL in cancer cell lines. J Biol Life Sci. 2014; 5(1): 1-11.
Al-Shammari AM, Abdullah AH, Allami ZM, Yaseen NY. 2-Deoxyglucose and Newcastle disease virus synergize to kill breast cancer cells by inhibition of glycolysis pathway through glyceraldehyde3-phosphate downregulation. Front. Mol. Biosci. 2019; 6: 90.
Kumar S, Gao L, Yeagy B, Reid T. Virus combinations and chemotherapy for the treatment of human cancers. CURR OPIN MOL THER. 2008; 10(4): 371-379.
Al-Shammari AM, Abo-Altemen RA, Shawkat MS. Cyperus rotundus L. alkaloid extracts enhance oncolytic Newcastle disease virus against digestive system neoplasms. S. Afr. J. Bot. 2021; 143: 266-73.
Salih RH, Odisho SM, Al-Shammari AM, Ibrahem OMS. Antiviral effects of Olea europaea leaves extract and interferon-beta on gene expression of Newcastle disease virus. Adv Anim Vet Sci. 2017; 5(11): 436-445.
Al-Shammari AM, Jalill RDA, Hussein MF. Combined therapy of oncolytic Newcastle disease virus and rhizomes extract of Rheum ribes enhances cancer virotherapy in vitro and in vivo. Mol. Biol. Rep. 2020; 47(3): 1691-1702.
Al-Shamery AM, Nahi YY, Alwan MJ. Establishment and characterization of AN3 first murine mammary adenocarcinoma transplantable tumor line in Iraq. Iraqi J. Cancer. 2008; 1(2): 1-10.
Huang CC, Wang SY, Lin LL, Wang PW, Chen TY, Hsu WM, et al. Glycolytic inhibitor 2-deoxyglucose simultaneously targets cancer and endothelial cells to suppress neuroblastoma growth in mice. Dis Model Mech. 2015; 8(10): 1247-1254.
Al-Shammari A, Yaseen N, Alwan M. Immunology study for NDV treatment in mice bearing mammary adenocarcinoma tumor. Iraqi J Cancer Med Genet. 2011; 4(1): 11-21.
Phuangsab A, Lorence RM, Reichard KW, Peeples ME, Walter RJ. Newcastle disease virus therapy of human tumor xenografts: antitumor effects of local or systemic administration. Cancer Lett. 2001; 172(1): 27-36.
Mustafa HN, El Awdan SA, Hegazy GA, Abdel Jaleel GA. Prophylactic role of coenzyme Q10 and Cynara scolymus L on doxorubicin-induced toxicity in rats: Biochemical and immunohistochemical study. Indian J Pharmacol. 2015; 47(6): 649-656.
Ahmad IM, Aykin-Burns N, Sim JE, Walsh SA, Higashikubo R, Buettner GR, et al. Mitochondrial O2*- and H2O2 mediate glucose deprivation-induced stress in human cancer cells. J Biol Chem. 2005; 280(6): 4254-4263.
Hsu PP, Sabatini DM. Cancer cell metabolism: Warburg and beyond. Cell. 2008;134(5):703-707.
Cairns RA, Harris I, McCracken S, Mak TW. Cancer cell metabolism. Cold Spring Harb. Symp. Quant. Biol. 2011; 76: 299-311.
Yurchenko KS, Zhou P, Kovner AV, Zavjalov EL, Shestopalova LV, Shestopalov AM. Oncolytic effect of wild-type Newcastle disease virus isolates in cancer cell lines in vitro and in vivo on xenograft model. PLoS One. 2018; 13(4): e0195425.
Al-Shammari AM, Yaseen NY, Alwan MJ. Newcastle Disease virus Iraqi oncolytic strain induce apoptosis in tumor cells through endoplasmic reticulum pathway. Iraqi J Cancer Med Genet. 2012; 5(1): 34-41.
Cheong J-H, Park ES, Liang J, Dennison JB, Tsavachidou D, Nguyen-Charles C, et al. Dual inhibition of tumor energy pathway by 2-deoxyglucose and metformin is effective against a broad spectrum of preclinical cancer models. Mol. Cancer Ther. 2011; 10(12): 2350-62.
Zhang D, Li J, Wang F, Hu J, Wang S, Sun Y. 2-Deoxy-D-glucose targeting of glucose metabolism in cancer cells as a potential therapy. Cancer Lett. 2014; 355(2): 176-83.
Dai S, Peng Y, Zhu Y, Xu D, Zhu F, Xu W, et al. Glycolysis promotes the progression of pancreatic cancer and reduces cancer cell sensitivity to gemcitabine. Biomed Pharmacother. 2020; 121: 109521.
Smith TA. Mammalian hexokinases and their abnormal expression in cancer. Br. J. Biomed. Sci. 2000; 57(2): 170-178.
Al-Ziaydi AG, Al-Shammari AM, Hamzah M, kadhim HS, Jabir MS. Hexokinase inhibition using D-Mannoheptulose enhances oncolytic newcastle disease virus-mediated killing of breast cancer cells. Cancer Cell Int. 2020; 20: 420.
Al-Ziaydi AG, Al-Shammari AM, Hamzah M, Kadhim HS, Jabir MS. Newcastle disease virus suppress glycolysis pathway and induce breast cancer cells death. Virusdisease. 2020; 31(3): 341-348.
Aykin-Burns N, Ahmad IM, Zhu Y, Oberley LW, Spitz DR. Increased levels of superoxide and H2O2 mediate the differential susceptibility of cancer cells versus normal cells to glucose deprivation. Biochem J. 2009; 418(1): 29-37.
Ahmad IM, Mustafa EH, Mustafa NH, Tahtamouni LH, Abdalla MY. 2DG enhances the susceptibility of breast cancer cells to doxorubicin. Central European Journal of Biology. 2010; 5(6): 739-748.
Kan X, Yin Y, Song C, Tan L, Qiu X, Liao Y, et al. Newcastle disease virus induced ferroptosis through p53-SLC7A11-GPX4 axis mediated nutrient deprivation in tumor cells. bioRxiv. 2021: 2021.01.03.424919.
Pfeffer CM, Singh AT. Apoptosis: a target for anticancer therapy. Int. J. Mol. Sci. 2018; 19(2): 448.
Mohammed MS, Al-Taee MF, Al-Shammari AM. Caspase dependent and independent anti-hematological malignancy activity of AMHA1 attenuated Newcastle disease virus. Int J Mol Cell Med. 2019; 8(3): 211-223.
Ishino K, Kudo M, Peng WX, Kure S, Kawahara K, Teduka K, et al. 2-Deoxy-d-glucose increases GFAT1 phosphorylation resulting in endoplasmic reticulum-related apoptosis via disruption of protein N-glycosylation in pancreatic cancer cells. Biochem. Biophys. Res. Commun. 2018; 501(3): 668-673.
Liu H, Jiang CC, Lavis CJ, Croft A, Dong L, Tseng HY, et al. 2-Deoxy-D-glucose enhances TRAIL-induced apoptosis in human melanoma cells through XBP-1-mediated up-regulation of TRAIL-R2. Mol. Cancer. 2009; 8(1): 122.
Shafaee A, Pirayesh Islamian J, Zarei D, Mohammadi M, Nejati-Koshki K, Farajollahi A, et al. Induction of apoptosis by a combination of 2-Deoxyglucose and metformin in esophageal squamous cell carcinoma by targeting cancer cell metabolism. Iran J Med Sci. 2019; 44(2): 99-107.