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Berberine suppresses in vitro migration and invasion of human SCC-4 tongue squamous cancer cells through the inhibitions of FAK, IKK, NF-kappaB, u-PA and MMP-2 and -9. Ho YT, Yang JS, Li TC, Lin JJ, Lin JG, Lai KC, Ma CY, Wood WG, Chung JG. Cancer Lett. 2009 Jul 8;279(2):155-62. Epub 2009 Feb 28. PMID: 19251361 doi:10.1016/j.canlet.2009.01.033 There is increasing evidence that urokinase-type plasminogen activator (u-PA) and matrix metalloproteinases (MMPs) play an important role in cancer metastasis and angiogenesis. Inhibition of u-PA and MMPs could suppress migration and invasion of cancer cells. Berberine, one of the main constituents of the plant Rhizoma coptidis, is a type of isoquinoline alkaloid, reported to have anti-cancer effects in different human cancer cell lines. There is however, no available information on effects of berberine on migration and invasion of human tongue cancer cells. Here, we report that berberine inhibited migration and invasion of human SCC-4 tongue squamous carcinoma cells. This action was mediated by the p-JNK, p-ERK, p-p38, IκK and NF-κB signaling pathways resulting in inhibition of MMP-2 and -9 in human SCC-4 tongue squamous carcinoma cells. Our Western blowing analysis also showed that berberine inhibited the levels of urokinase-plasminogen activator (u-PA). These results suggest that berberine down-regulates u-PA, MMP-2 and -9 expressions in SCC-4 cells through the FAK, IKK and NF-κB mediated pathways and a novel function of berberine is to inhibit the invasive capacity of malignant cells.

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.

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]

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 of an EGFR blocker and a COX-2 inhibitor for the treatment of advanced cutaneous squamous cell carcinoma. Jalili A, Pinc A, Pieczkowski F, Karlhofer FM, Stingl G, Wagner SN. J Dtsch Dermatol Ges. 2008 Dec;6(12):1066-9. English, German. PMID: 19138272 DOI: 10.1111/j.1610-0387.2008.06861.x

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

Berberine inhibits human tongue squamous carcinoma cancer tumor growth in a murine xenograft model. Ho YT, Yang JS, Lu CC, Chiang JH, Li TC, Lin JJ, Lai KC, Liao CL, Lin JG, Chung JG. Phytomedicine. 2009 Sep;16(9):887-90. Epub 2009 Mar 20. PMID: 19303753 Our primary studies showed that berberine induced apoptosis in human tongue cancer SCC-4 cells in vitro. But there is no report to show berberine inhibited SCC-4 cancer cells in vivo on a murine xenograft animal model. SCC-4 tumor cells were implanted into mice and groups of mice were treated with vehicle, berberine (10mg/kg of body weight) and doxorubicin (4mg/kg of body weight). The tested agents were injected once per four days intraperitoneally (i.p.), with treatment starting 4 weeks prior to cells inoculation. Treatment with 4mg/kg of doxorubicin or with 10mg/kg of berberine resulted in a reduction in tumor incidence. Tumor size in xenograft mice treated with 10mg/kg berberine was significantly smaller than that in the control group. Our findings indicated that berbeirne inhibits tumor growth in a xenograft animal model. Therefore, berberine may represent a tongue cancer preventive agent and can be used in clinic.

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

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

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

Higher blood levels of selenium may reduce the incidence of skin cancer by about 60 per cent, according to a new study from Dutch and Australian researchers. Writing in Cancer Epidemiology, Biomarkers & Prevention, the researchers report that the mineral was associated with reduced risks of both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). On the other hand, blood levels of carotenoids and alpha-tocopherol (vitamin E) were not associated with any influence on skin cancer risks, report the researchers from Queensland Institute of Medical Research, the University of Queensland, and Maastricht University.

Roughly 10 percent of Americans continue to use indoor tanning beds, but new research suggests that doing so increases their risk for three common skin cancers, including basal cell carcinoma, squamous cell carcinoma and melanoma.