The Role of Dysregulated Glucose Metabolism in Epithelial Ovarian Cancer

Overview

Journal J Oncol

Specialty Oncology

Date 2010 Feb 26

PMID 20182531

Citations 28

Authors

L D Kellenberger

J E Bruin

J Greenaway

N E Campbell

R A Moorehead

A C Holloway

J Petrik

Affiliations

Soon will be listed here.

Abstract

Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer and also one of the most poorly understood. Other health issues that are affecting women with increasing frequency are obesity and diabetes, which are associated with dysglycemia and increased blood glucose. The Warburg Effect describes the ability of fast-growing cancer cells to preferentially metabolize glucose via anaerobic glycolysis rather than oxidative phosphorylation. Recent epidemiological studies have suggested a role for hyperglycemia in the pathogenesis of a number of cancers. If hyperglycemia contributes to tumour growth and progression, then it is intuitive that antihyperglycemic drugs may also have an important antitumour role. Preliminary reports suggest that these drugs not only reduce available plasma glucose, but also have direct effects on cancer cell viability through modification of molecular energy-sensing pathways. This review investigates the effect that hyperglycemia may have on EOC and the potential of antihyperglycemic drugs as therapeutic adjuncts.

Citing Articles

Role of Receptor for Advanced Glycation End-Products in Endometrial Cancer: A Review.

Zglejc-Waszak K, Jozwik M, Thoene M, Wojtkiewicz J Cancers (Basel). 2024; 16(18).

PMID: 39335163 PMC: 11430655. DOI: 10.3390/cancers16183192.

Metabolism changes caused by glucose in normal and cancer human brain cell lines by Raman imaging and chemometric methods.

Kopec M, Beton-Mysur K, Surmacki J, Abramczyk H Sci Rep. 2024; 14(1):16626.

PMID: 39025939 PMC: 11258355. DOI: 10.1038/s41598-024-67718-y.

Cell-free ascites from ovarian cancer patients induces Warburg metabolism and cell proliferation through TGFβ-ERK signaling.

Szeocs D, Vida B, Petovari G, Poliska S, Janka E, Sipos A Geroscience. 2024; 46(4):3581-3597.

PMID: 38196068 PMC: 11226691. DOI: 10.1007/s11357-023-01056-1.

Diabetes and ovarian cancer: risk factors, molecular mechanisms and impact on prognosis.

Karimi F, Dinarvand N, Sabaghan M, Azadbakht O, Ataee S, Kharazinejad E Endocrine. 2023; 83(1):1-9.

PMID: 37552417 DOI: 10.1007/s12020-023-03477-6.

[Diabetes mellitus and the female reproductive system tumors].

Sharafutdinova K, Shlyapina V, Baeva A, Timurshin A, Sabanaeva I, Nakieva A Probl Endokrinol (Mosk). 2023; 69(3):103-110.

PMID: 37448252 PMC: 10350608. DOI: 10.14341/probl13282.

References

Doblado M, Moley K . Glucose metabolism in pregnancy and embryogenesis. Curr Opin Endocrinol Diabetes Obes. 2007; 14(6):488-93. DOI: 10.1097/MED.0b013e3282f1cb92. View

Puckett C, SHINGLETON W . The effect of induced diabetes on experimental tumor growth in mice. Cancer Res. 1972; 32(4):789-90. View

Kueck A, Opipari Jr A, Griffith K, Tan L, Choi M, Huang J . Resveratrol inhibits glucose metabolism in human ovarian cancer cells. Gynecol Oncol. 2007; 107(3):450-7. DOI: 10.1016/j.ygyno.2007.07.065. View

Hahn T, Barth S, Hofmann W, Reich O, Lang I, Desoye G . Hyperglycemia regulates the glucose-transport system of clonal choriocarcinoma cells in vitro. A potential molecular mechanism contributing to the adjunct effect of glucose in tumor therapy. Int J Cancer. 1998; 78(3):353-60. DOI: 10.1002/(SICI)1097-0215(19981029)78:3<353::AID-IJC16>3.0.CO;2-7. View

Stackhouse M, Buchsbaum D, Kancharla S, Grizzle W, Grimes C, Laffoon K . Specific membrane receptor gene expression targeted with radiolabeled peptide employing the erbB-2 and DF3 promoter elements in adenoviral vectors. Cancer Gene Ther. 1999; 6(3):209-19. DOI: 10.1038/sj.cgt.7700049. View

Brown R, Wahl R . Overexpression of Glut-1 glucose transporter in human breast cancer. An immunohistochemical study. Cancer. 1993; 72(10):2979-85. DOI: 10.1002/1097-0142(19931115)72:10<2979::aid-cncr2820721020>3.0.co;2-x. View

Esposito K, Nappo F, Marfella R, Giugliano G, Giugliano F, Ciotola M . Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: role of oxidative stress. Circulation. 2002; 106(16):2067-72. DOI: 10.1161/01.cir.0000034509.14906.ae. View

Kunkel M, Moergel M, Stockinger M, Jeong J, Fritz G, Lehr H . Overexpression of GLUT-1 is associated with resistance to radiotherapy and adverse prognosis in squamous cell carcinoma of the oral cavity. Oral Oncol. 2007; 43(8):796-803. DOI: 10.1016/j.oraloncology.2006.10.009. View

Belotti D, Paganoni P, Manenti L, Garofalo A, Marchini S, Taraboletti G . Matrix metalloproteinases (MMP9 and MMP2) induce the release of vascular endothelial growth factor (VEGF) by ovarian carcinoma cells: implications for ascites formation. Cancer Res. 2003; 63(17):5224-9. View

10.

Helmke B, Reisser C, Idzko M, Dyckhoff G, Herold-Mende C, Idzkoe M . Expression of SGLT-1 in preneoplastic and neoplastic lesions of the head and neck. Oral Oncol. 2003; 40(1):28-35. DOI: 10.1016/s1368-8375(03)00129-5. View

11.

Ness R, Cottreau C . Possible role of ovarian epithelial inflammation in ovarian cancer. J Natl Cancer Inst. 1999; 91(17):1459-67. DOI: 10.1093/jnci/91.17.1459. View

12.

Huang S, Robinson J, Deguzman A, Bucana C, Fidler I . Blockade of nuclear factor-kappaB signaling inhibits angiogenesis and tumorigenicity of human ovarian cancer cells by suppressing expression of vascular endothelial growth factor and interleukin 8. Cancer Res. 2000; 60(19):5334-9. View

13.

Grosios K, Wood J, Esser R, Raychaudhuri A, Dawson J . Angiogenesis inhibition by the novel VEGF receptor tyrosine kinase inhibitor, PTK787/ZK222584, causes significant anti-arthritic effects in models of rheumatoid arthritis. Inflamm Res. 2004; 53(4):133-42. DOI: 10.1007/s00011-003-1230-4. View

14.

Kalli K, Falowo O, Bale L, Zschunke M, Roche P, Conover C . Functional insulin receptors on human epithelial ovarian carcinoma cells: implications for IGF-II mitogenic signaling. Endocrinology. 2002; 143(9):3259-67. DOI: 10.1210/en.2001-211408. View

15.

Yuan J, Narayanan L, Rockwell S, Glazer P . Diminished DNA repair and elevated mutagenesis in mammalian cells exposed to hypoxia and low pH. Cancer Res. 2000; 60(16):4372-6. View

16.

Cowey S, Hardy R . The metabolic syndrome: A high-risk state for cancer?. Am J Pathol. 2006; 169(5):1505-22. PMC: 1780220. DOI: 10.2353/ajpath.2006.051090. View

17.

Cramer D, Kuper H, Harlow B, Titus-Ernstoff L . Carotenoids, antioxidants and ovarian cancer risk in pre- and postmenopausal women. Int J Cancer. 2001; 94(1):128-34. DOI: 10.1002/ijc.1435. View

18.

Lamkin D, Spitz D, Shahzad M, Zimmerman B, Lenihan D, DeGeest K . Glucose as a prognostic factor in ovarian carcinoma. Cancer. 2009; 115(5):1021-7. PMC: 2649990. DOI: 10.1002/cncr.24126. View

19.

Kallinowski F, Vaupel P, Runkel S, Berg G, FORTMEYER H, BAESSLER K . Glucose uptake, lactate release, ketone body turnover, metabolic micromilieu, and pH distributions in human breast cancer xenografts in nude rats. Cancer Res. 1988; 48(24 Pt 1):7264-72. View

20.

Okumura M, Yamamoto M, Sakuma H, Kojima T, Maruyama T, Jamali M . Leptin and high glucose stimulate cell proliferation in MCF-7 human breast cancer cells: reciprocal involvement of PKC-alpha and PPAR expression. Biochim Biophys Acta. 2002; 1592(2):107-16. DOI: 10.1016/s0167-4889(02)00276-8. View