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Simultaneously Blocking Glycolysis and Fat Metabolism Can the use of DCA and a fatty acid metabolism blocker together force more cancer cells into using aerobic metabolism? Tim McGough used green tea extract, which contains EGCG, in his fantastic response. DCA works by reactivating mitochondria and shifts metabolism from glycolysis to glucose oxidation. Hopefully the cancer cell will then undergo apoptosis. However, cancer cells have an alternate energy source: fat metabolism. This page explores to possibility of blocking fat metabolism to help force the cell into apoptosis. Oral squamous cell carcinoma is a cancer that does not respond well to DCA. This study, Head and Neck Cancer Cell Lines Are Resistant to Mitochondrial-Depolarization-Induced Apoptosis states: "Results: ΔΨm in head and neck cell lines started to show slight loss of ΔΨm, while HL-60 showed significant loss of ΔΨm after 30 min of treatment. All cell lines demonstrated complete mitochondrial depolarization within 24 h, however, only the control cell line HL-60 underwent apoptosis. In addition, HNSCC cell lines did not demonstrate cytoplasmic cytochrome c release despite significant mitochondrial membrane depolarization, while HL-60 cell initiated apoptosis and cytochcrome c release after 24 h of treatment. Conclusions: Head and neck cancer cell lines exhibit defects in mitochondrial-membrane-depolarization-induced apoptosis as well as impaired release of cytochrome c despite significant mitochondrial membrane depolarization. Proximal defects in the mitochondrial apoptosis pathway are a feature of HNSCC.(head and neck squamous cell carcinoma)" Note that although the cell lines were depolarized, apoptosis did not occur. So I checked to see if fatty acid metabolism is used by squamous cell carcinoma.

Schroeder CP, Yang P, Newman RA, Lotan R. Eicosanoid metabolism in squamous cell carcinoma cell lines derived from primary and metastatic head and neck cancer and its modulation by celecoxib. Cancer Biol Ther. 2004 Sep;3(9):847-52. Epub 2004 Sep 18. P

Scheper MA, Nikitakis NG, Chaisuparat R, Montaner S, Sauk JJ. Sulindac Induces Apoptosis and Inhibits Tumor Growth in vivo in Head and Neck Squamous Cell Carcinoma. Neoplasia. 2007 Mar;9(3):192-9. PMID: 17401459 [PubMed - in process]

C. Cox, S. D. Merajver, S. Yoo, R. D. Dick, G. J. Brewer, J. S.-J. Lee, and T. N. Teknos Inhibition of the Growth of Squamous Cell Carcinoma by Tetrathiomolybdate-Induced Copper Suppression in a Murine Model Arch Otolaryngol Head Neck Surg, July 1, 200

Awada A, Ismael G. The challenging integration of platinum compounds, taxanes, and molecular-targeted therapies in the multidisciplinary treatment of squamous cell carcinoma of the head and neck. Curr Opin Oncol. 2007 May;19(3):177-9. PMID: 17414633 [

Combination immunotherapy of squamous cell carcinoma of the head and neck: a phase 2 trial. Barrera JL, Verastegui E, Meneses A, Zinser J, de la Garza J, Hadden JW. Arch Otolaryngol Head Neck Surg. 2000 Mar;126(3):345-51. PMID: 10722007

Simultaneously targeting epidermal growth factor receptor tyrosine kinase and cyclooxygenase-2, an efficient approach to inhibition of squamous cell carcinoma of the head and neck. Chen Z, Zhang X, Li M, Wang Z, Wieand HS, Grandis JR, Shin DM. Clin Cancer Res. 2004 Sep 1;10(17):5930-9. PMID: 15355926

Development of HPV vaccines for HPV-associated head and neck squamous cell carcinoma. Devaraj K, Gillison ML, Wu TC. Crit Rev Oral Biol Med. 2003;14(5):345-62. Review. PMID: 14530303

Antitumor activity of human papillomavirus type 16 E7-specific T cells against virally infected squamous cell carcinoma of the head and neck. Albers A, Abe K, Hunt J, Wang J, Lopez-Albaitero A, Schaefer C, Gooding W, Whiteside TL, Ferrone S, DeLeo A, Ferris RL. Cancer Res. 2005 Dec 1;65(23):11146-55. PMID: 16322265

Factors associated with clinical benefit from epidermal growth factor receptor inhibitors in recurrent and metastatic squamous cell carcinoma of the head and neck. Cohen EE, Halpern AB, Kasza K, Kocherginsky M, Williams R, Vokes EE. Oral Oncol. 2009 Oct;45(10):e155-60. Epub 2009 Jul 7. PMID: 19586795

Yeudall WA, Miyazaki H. Chemokines and squamous cancer of the head and neck: targets for therapeutic intervention? Expert Rev Anticancer Ther. 2007 Mar;7(3):351-60. PMID: 17338654 [PubMed - in process]