Biochemical Origin of the Warburg Effect in Light of 15 Years of Research Experience: A Novel Evidence-Based View (An Expert Opinion Article)

References

• Yaku K, Okabe K, Hikosaka K, Nakagawa T. NAD metabolism in cancer therapeutics. Front Oncol. 2018;8:622. doi:10.3389/fonc.2018.00622
   PubMed Web of Science ®Google Scholar
• Lu J, Tan M, Cai Q. The Warburg effect in tumor progression: mitochondrial oxidative metabolism as an anti-metastasis mechanism. Cancer Lett. 2015;356:156–164. doi:10.1016/j.canlet.2014.04.001
   PubMed Web of Science ®Google Scholar
• Otto AM. Warburg effect (s)—a biographical sketch of Otto Warburg and his impacts on tumor metabolism. Cancer Metab. 2016;4:1–8. doi:10.1186/s40170-016-0145-9
   Google Scholar
• El Sayed SM, Mohamed WG, Seddik M-AH, et al. Safety and outcome of treatment of metastatic melanoma using 3-bromopyruvate: a concise literature review and case study. Chin J Cancer. 2014;33:356. doi:10.5732/cjc.013.10111
   PubMedGoogle Scholar
• El Sayed SM, Mahmoud AA, El Sawy SA, et al. Warburg effect increases steady-state ROS condition in cancer cells through decreasing their antioxidant capacities (anticancer effects of 3-bromopyruvate through antagonizing Warburg effect). Med Hypotheses. 2013;81:866–870. doi:10.1016/j.mehy.2013.08.024
   PubMed Web of Science ®Google Scholar
• Xie J, Wu H, Dai C, et al. Beyond Warburg effect–dual metabolic nature of cancer cells. Sci Rep. 2014;4:1–12. doi:10.1038/srep04927
   Web of Science ®Google Scholar
• Druzhkova IN, Shirmanova MV, Lukina MM, Dudenkova VV, Mishina NM, Zagaynova EV. The metabolic interaction of cancer cells and fibroblasts–coupling between NAD (P) H and FAD, intracellular pH and hydrogen peroxide. Cell Cycle. 2016;15:1257–1266. doi:10.1080/15384101.2016.1160974
   PubMed Web of Science ®Google Scholar
• Ishikawa M, Inoue T, Shirai T, et al. Simultaneous expression of cancer stem cell-like properties and cancer-associated fibroblast-like properties in a primary culture of breast cancer cells. Cancers. 2014;6:1570–1578. doi:10.3390/cancers6031570
   PubMed Web of Science ®Google Scholar
• Abdel-Wahab AF, Mahmoud W, Al-Harizy RM. Targeting glucose metabolism to suppress cancer progression: prospective of anti-glycolytic cancer therapy. Pharmacol Res. 2019;150:104511. doi:10.1016/j.phrs.2019.104511
   PubMed Web of Science ®Google Scholar
• Zhang X, Guo J, Kaboli PJ, et al. Analysis of key genes regulating the Warburg effect in patients with gastrointestinal cancers and selective inhibition of this metabolic pathway in liver cancer cells. Onco Targets Ther. 2020;13:7295. doi:10.2147/OTT.S257944
   PubMed Web of Science ®Google Scholar
• Jurisic V, Radenkovic S, Konjevic G. The actual role of LDH as tumor marker, biochemical and clinical aspects. Adv Cancer Biomarkers. 2015;1:115–124.
   Google Scholar
• Bacci G, Avella M, McDonald D, Toni A, Orlandi M, Campanacci M. Serum lactate dehydrogenase (LDH) as a tumor marker in Ewing’s sarcoma. Tumori J. 1988;74:649–655. doi:10.1177/030089168807400606
   PubMed Web of Science ®Google Scholar
• El Sayed S, Abou El-Magd R, Shishido Y, et al. 3-Bromopyruvate antagonizes effects of lactate and pyruvate, synergizes with citrate and exerts novel anti-glioma effects. J Bioenerg Biomembr. 2012;44:61–79. doi:10.1007/s10863-012-9409-4
   PubMed Web of Science ®Google Scholar
• El Sayed S, Abou El-Magd R, Shishido Y, et al. D-Amino acid oxidase-induced oxidative stress, 3-bromopyruvate and citrate inhibit angiogenesis, exhibiting potent anticancer effects. J Bioenerg Biomembr. 2012;44:513–523. doi:10.1007/s10863-012-9455-y
   PubMed Web of Science ®Google Scholar
• El Sayed S, El-Magd A, Shishido Y, et al. D-amino acid oxidase gene therapy sensitizes glioma cells to the antiglycolytic effect of 3-bromopyruvate. Cancer Gene Ther. 2012;19:1–18. doi:10.1038/cgt.2011.59
   PubMed Web of Science ®Google Scholar
• Gasparre G, Porcelli AM, Lenaz G, Romeo G. Relevance of mitochondrial genetics and metabolism in cancer development. Cold Spring Harb Perspect Biol. 2013;5:a011411. doi:10.1101/cshperspect.a011411
   PubMed Web of Science ®Google Scholar
• Kennedy BE, Sharif T, Martell E, et al. NAD+ salvage pathway in cancer metabolism and therapy. Pharmacol Res. 2016;114:274–283. doi:10.1016/j.phrs.2016.10.027
   PubMed Web of Science ®Google Scholar
• Ju H-Q, Zhuang Z-N, Li H, et al. Regulation of the Nampt-mediated NAD salvage pathway and its therapeutic implications in pancreatic cancer. Cancer Lett. 2016;379:1–11. doi:10.1016/j.canlet.2016.05.024
   PubMed Web of Science ®Google Scholar
• Zhu S, Dong Z, Ke X. The roles of sirtuins family in cell metabolism during tumor development. Semin Cancer Biol. 2019;59:71
   Google Scholar
• Kleszcz R, Paluszczak J, Baer-Dubowska W. Targeting aberrant cancer metabolism–The role of sirtuins. Pharmacol Rep. 2015;67:1068–1080. doi:10.1016/j.pharep.2015.03.021
   PubMed Web of Science ®Google Scholar
• Keshari KR, Wilson DM, Van Criekinge M, et al. Metabolic response of prostate cancer to nicotinamide phophoribosyltransferase inhibition in a hyperpolarized MR/PET compatible bioreactor. Prostate. 2015;75:1601–1609. doi:10.1002/pros.23036
   PubMed Web of Science ®Google Scholar
• Liu K, Tang Z, Huang A, et al. Glyceraldehyde-3-phosphate dehydrogenase promotes cancer growth and metastasis through upregulation of SNAIL expression. Int J Oncol. 2017;50:252–262. doi:10.3892/ijo.2016.3774
   PubMed Web of Science ®Google Scholar
• Pathria G, Scott DA, Feng Y, et al. Targeting the Warburg effect via LDHA inhibition engages ATF 4 signaling for cancer cell survival. EMBO J. 2018;37:e99735. doi:10.15252/embj.201899735
   PubMed Web of Science ®Google Scholar
• Feng Y, Xiong Y, Qiao T, Li X, Jia L, Han Y. Lactate dehydrogenase A: a key player in carcinogenesis and potential target in cancer therapy. Cancer Med. 2018;7:6124–6136. doi:10.1002/cam4.1820
   PubMed Web of Science ®Google Scholar
• Reddy MA, Shukla SD. Nuclear activation and translocation of mitogen-activated protein kinases modulated by ethanol in embryonic liver cells. Mol Cell Res. 2000;1497:271–278. doi:10.1016/S0167-4889(00)00058-6
   PubMed Web of Science ®Google Scholar
• Fiume L, Manerba M, Vettraino M, Di Stefano G. Inhibition of lactate dehydrogenase activity as an approach to cancer therapy. Future Med Chem. 2014;6:429–445. doi:10.4155/fmc.13.206
   PubMed Web of Science ®Google Scholar
• Brooks GA, Dubouchaud H, Brown M, Sicurello JP, Butz CE. Role of mitochondrial lactate dehydrogenase and lactate oxidation in the intracellular lactate shuttle. Proc National Acad Sci. 1999;96:1129–1134. doi:10.1073/pnas.96.3.1129
   PubMed Web of Science ®Google Scholar
• Icard P, Lincet H. The cancer tumor: a metabolic parasite? Bull Cancer. 2013;100:427–433. doi:10.1684/bdc.2013.1742
   PubMed Web of Science ®Google Scholar
• Marquez J, Kratchmarova I, Akimov V, et al. NADH dehydrogenase complex I is overexpressed in incipient metastatic murine colon cancer cells. Oncol Rep. 2019;41:742–752. doi:10.3892/or.2018.6892
   PubMed Web of Science ®Google Scholar
• Koukourakis MI, Giatromanolaki A, Sivridis E, et al. Lactate dehydrogenase-5 (LDH-5) overexpression in non-small-cell lung cancer tissues is linked to tumour hypoxia, angiogenic factor production and poor prognosis. Br J Cancer. 2003;89:877–885. doi:10.1038/sj.bjc.6601205
   PubMed Web of Science ®Google Scholar
• Semenza GL, Jiang B-H, Leung SW, et al. Hypoxia response elements in the aldolase A, enolase 1, and lactate dehydrogenase A gene promoters contain essential binding sites for hypoxia-inducible factor 1. J Biol Chem. 1996;271:32529–32537. doi:10.1074/jbc.271.51.32529
   PubMed Web of Science ®Google Scholar
• Dang CV, Kim JW, Gao P, Yustein J. The interplay between MYC and HIF in cancer. Nat Rev Cancer. 2008;8:51–56. doi:10.1038/nrc2274
   PubMed Web of Science ®Google Scholar
• Warburg O. On the origin of cancer cells. Science. 1956;123:309–314. doi:10.1126/science.123.3191.309
   PubMed Web of Science ®Google Scholar
• Abdullah A, Abdelsalam E, Abdullah B, Khaled A. Antioxidant effects of Zamzam water in normal rats and those under induced-oxidative stress. J Med Plants Res. 2012;6:5507–5512.
   Google Scholar
• Mahmoud HS, Eltahlawi RA, Alhadramy O, et al. Zamzam water is pathogen-free, cardioprotective and tissue-protective: relieving the BBC concerns. Am J Clin Med Res. 2020;8:5–12.
   Google Scholar
• Mahmoud HS, Eltahlawi RA, Jan AA, et al. Zamzam water is pathogen-free, uricosuric, hypolipidemic and exerts tissue-protective effects: relieving BBC concerns. Am J Blood Res. 2020;10:386.
   PubMed Web of Science ®Google Scholar
• Zergui A, Aledeh M, Hamad S. Metallic profile of Zamzam water: determination of minerals, metals and metalloids by ICP-MS. J Trace Elements Minerals. 2022;2:100031. doi:10.1016/j.jtemin.2022.100031
   Google Scholar
• Hassan SMA, Aboonq MS, Albadawi EA, et al. The Preventive and Therapeutic Effects of Ajwa Date Fruit Extract Against Acute Diclofenac Toxicity-Induced Colopathy: an Experimental Study. Drug Des Devel Ther. 2022;16:2601. doi:10.2147/DDDT.S344247
   PubMed Web of Science ®Google Scholar
• Khan F, Khan TJ, Kalamegam G, et al. Anti-cancer effects of Ajwa dates (Phoenix dactylifera L.) in diethylnitrosamine induced hepatocellular carcinoma in Wistar rats. BMC Complement Altern Med. 2017;17:1–10. doi:10.1186/s12906-017-1926-6
   PubMed Web of Science ®Google Scholar
• El-Shanshory M, Hablas NM, Aboonq MS, et al. Nigella sativa improves anemia, enhances immunity and relieves iron overload-induced oxidative stress as a novel promising treatment in children having beta-thalassemia major. J Herbal Med. 2019;16:100245. doi:10.1016/j.hermed.2018.11.001
   Web of Science ®Google Scholar
• Ahmad A, Husain A, Mujeeb M, et al. A review on therapeutic potential of Nigella sativa: a miracle herb. Asian Pac J Trop Biomed. 2013;3:337–352. doi:10.1016/S2221-1691(13)60075-1
   PubMedGoogle Scholar
• El Sayed SM, Baghdadi H, Abou-Taleb A, et al. Al-hijamah and oral honey for treating thalassemia, conditions of iron overload, and hyperferremia: toward improving the therapeutic outcomes. J Blood Med. 2014;5:219. doi:10.2147/JBM.S65042
   PubMedGoogle Scholar
• Almasaudi SB, El-Shitany NA, Abbas AT, Abdel-dayem UA, Ali SS, Al Jaouni SK. Antioxidant, anti-inflammatory, and antiulcer potential of manuka honey against gastric ulcer in rats. Oxid Med Cell Longev. 2016;2016:1–10. doi:10.1155/2016/3643824
   Web of Science ®Google Scholar
• El Sayed SM, Bahashwan S, Aboonq M, et al. Adjuvant TaibUVID nutritional supplements proved promising for novel safe COVID-19 public prophylaxis and treatment: enhancing immunity and decreasing morbidity period for better outcomes (A retrospective study). Int J Med Develop Countries. 2020;4:1375–1389. doi:10.24911/IJMDC.51-1594011487
   Google Scholar
• El Sayed SM, Almaramhy HH, Aljehani YT, et al. The evidence-based TaibUVID nutritional treatment for minimizing COVID-19 fatalities and morbidity and eradicating COVID-19 pandemic: a novel Approach for Better Outcomes (A Treatment Protocol). Am J Public Health Res. 2020;8:54–60.
   Google Scholar
• El Sayed SM, Aboonq MS, El Rashedy AG, et al. Promising preventive and therapeutic effects of TaibUVID nutritional supplements for COVID-19 pandemic: towards better public prophylaxis and treatment (A retrospective study). Am J Blood Res. 2020;10:266.
   PubMed Web of Science ®Google Scholar
• El Sayed SM, Aboonq MS, Aljehani YT, et al. TaibUVID nutritional supplements help rapid cure of COVID-19 infection and rapid reversion to negative nasopharyngeal swab PCR: for better public prophylaxis and treatment of COVID-19 pandemic. Am J Blood Res. 2020;10:397.
   PubMed Web of Science ®Google Scholar
• El-Shanshory M, Hablas NM, Shebl Y, et al. Al-hijamah (wet cupping therapy of prophetic medicine) significantly and safely reduces iron overload and oxidative stress in thalassemic children: a novel pilot study. J Blood Med. 2018;9:241. doi:10.2147/JBM.S170523
   PubMed Web of Science ®Google Scholar
• El-Shanshory M, Hablas NM, Shebel Y, et al. Al-hijamah (the triple S treatment of prophetic medicine) exerts cardioprotective, tissue-protective and immune potentiating effects in thalassemic children: a pilot clinical trial. Am J Blood Res. 2020;10:447.
   PubMed Web of Science ®Google Scholar
• El-Shanshory M, Hablas NM, El-Tahlawi R, et al. Al-hijamah (the triple S treatment of prophetic medicine) significantly increases CD4/CD8 ratio in thalassemic patients via increasing TAC/MDA ratio: a clinical trial. Am J Blood Res. 2022;12:125.
   PubMedGoogle Scholar
• Aboonq MS. Al-hijamah (wet cupping therapy of prophetic medicine) as a novel alternative to surgery for carpal tunnel syndrome. Neurosci J. 2019;24:137–141. doi:10.17712/nsj.2019.2.20180036
   Google Scholar
• Baghdadi H, Abdel-Aziz N, Ahmed NS, et al. Ameliorating role exerted by Al-Hijamah in autoimmune diseases: effect on serum autoantibodies and inflammatory mediators. Int J Health Sci. 2015;9:207. doi:10.12816/0024129
   Google Scholar
• Mahmoud HS, Abou-El-Naga M, Omar NAA, et al. Anatomical sites for practicing wet cupping therapy (Al-Hijamah): in light of modern medicine and prophetic medicine. Altern Integ Med. 2013;2:1–30.
   Google Scholar
• El Sayed SM, Mahmoud H, Nabo M. Medical and scientific bases of wet cupping therapy (Al-hijamah): in light of modern medicine and prophetic medicine. Alternative Integrative Med. 2013;25:1–16.
   Google Scholar
• El Sayed SM, Mahmoud HS, Nabo MMH. Methods of wet cupping therapy (Al-Hijamah): in light of modern medicine and prophetic medicine. Alternative Integrative Med. 2013;1–16.
   Google Scholar
• El Sayed SM, Abou-Taleb A, Mahmoud HS, et al. Percutaneous excretion of iron and ferritin (through Al-hijamah) as a novel treatment for iron overload in beta-thalassemia major, hemochromatosis and sideroblastic anemia. Med Hypotheses. 2014;83:238–246. doi:10.1016/j.mehy.2014.04.001
   PubMed Web of Science ®Google Scholar
• El Sayed SM, Al-quliti A-S, Mahmoud HS, et al. Therapeutic benefits of Al-hijamah: in light of modern medicine and prophetic medicine. Am J Med Biol Res. 2014;2:46–71. doi:10.12691/ajmbr-2-2-3
   Google Scholar