Growth Inhibition and Apoptosis with H31 Metabolites from Marine Bacillus SW31 in Head and Neck Cancer Cells
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Objectives. To determine whether a novel marine micro-organism with anticancer properties, H31, the metabolic product of Bacillus SW31, has anti-tumor effects on head and neck cancer, and potential for apoptotic-enhancing anti-cancer treatment of affected patients. Methods. The cell viability and apoptosis assays were performed. Changes in the signal pathway related to apoptosis were investigated. Then, the therapeutic effects of H31 were explored in mouse xenograft model and drug toxicity of H31was examined in zebrafish model. Results. We identified the anticancer activity of H31, a novel metabolic product of Bacillus SW31. Bacillus SW31, a new marine micro-organism, has 70% homology with Bacillus firmus and contains potent cytotoxic bioactivity in head and neck cancer cells using MTT assay. Combined with c-JUN, p53, cytochrome C, and caspase-3, H31 induced apoptosis of KB cells, a head and neck cancer cell line. In a separate in vivo model, tumor growth in C3H/HeJ syngeneic mice was suppressed by H31. In addition, in a zebrafish model used for toxicity testing, a considerable dose of H31 did not result in embryo or neurotoxicity. Conclusion. Growth inhibition and apoptosis were achieved both in vitro and in vivo in head and neck cancer cells after exposure to H31, a metabolite from the marine Bacillus species, without any significant toxicity effects even at considerable H31 dose concentrations.
Abstract
Objectives. To determine whether a novel marine micro-organism with anticancer properties, H31, the metabolic product of Bacillus SW31, has anti-tumor effects on head and neck cancer, and potential for apoptotic-enhancing anti-cancer treatment of affected patients. Methods. The cell viability and apoptosis assays were performed. Changes in the signal pathway related to apoptosis were investigated. Then, the therapeutic effects of H31 were explored in mouse xenograft model and drug toxicity of H31was examined in zebrafish model. Results. We identified the anticancer activity of H31, a novel metabolic product of Bacillus SW31. Bacillus SW31, a new marine micro-organism, has 70% homology with Bacillus firmus and contains potent cytotoxic bioactivity in head and neck cancer cells using MTT assay. Combined with c-JUN, p53, cytochrome C, and caspase-3, H31 induced apoptosis of KB cells, a head and neck cancer cell line. In a separate in vivo model, tumor growth in C3H/HeJ syngeneic mice was suppressed by H31. In addition, in a zebrafish model used for toxicity testing, a considerable dose of H31 did not result in embryo or neurotoxicity. Conclusion. Growth inhibition and apoptosis were achieved both in vitro and in vivo in head and neck cancer cells after exposure to H31, a metabolite from the marine Bacillus species, without any significant toxicity effects even at considerable H31 dose concentrations.
참고문헌 (30)
- Jemal A, "Cancer statistics,2008", CA Cancer J Clin, 58(2), pp.71~96 (2008)
- Argiris A, "Head and neck cancer", Lancet, 371(9625), pp.1695~1709 (2008)
- Forastiere AA, "Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer", N Engl J Med, 349(22), pp.2091~2098 (2003)
- Boulikas T, "Recent clinical trials using cisplatin,carboplatin and their combination chemotherapy drugs(review)", Oncol Rep, 11(3), pp.559~595 (2004)
- Bernan VS, "Marine microorganisms as a source of new natural products", Adv Appl Microbiol, 43, pp.57~90 (1997)
- Isnansetyo A, "MC21-A,a bactericidal antibiotic produced by a new marine bacterium,Pseudoalteromonas phenolica sp.nov.O-BC30(T),against methicillin-resistant Staphylococcus aureus", Antimicrob Agents Chemother, 47(2), pp.480~488 (2003)
- Blunt JW, "Marine natural products", Nat Prod Rep, 24(1), pp.31~86 (2007)
- Kim J, "Cytotoxic anticancer candidates from natural resources", Curr Med Chem Anticancer Agents, 2(4), pp.485~537 (2002)
- Singh B, "Molecular pathogenesis of head and neck cancers", J Surg Oncol, 97(8), pp.634~639 (2008)
- Gastman BR, "Apoptosis and its clinical impact", Head Neck, 23(5), pp.409~425 (2001)
- Rainey FA, "The genus Nocardiopsis represents a phylogenetically coherent taxon and a distinct actinomycete lineage:proposal of Nocardiopsaceae fam.nov", Int J Syst Bacteriol, 46(4), pp.1088~1092 (1996)
- Thompson JD, "CLUSTAL W:improving the sensitivity of progressive multiple sequence alignment through sequence weighting,position-specific gap penalties and weight matrix choice", Nucleic Acids Res, 22(22), pp.4673~4680 (1994)
- Kimura M, "A simple method for estimating evolutionary rates of base substitutions through comparative studies of nucleotide sequences", J Mol Evol, 16(2), pp.111~120 (1980)
- O’Malley BW Jr, "A new immunocompetent murine model for oral cancer", Arch Otolaryngol Head Neck Surg, 123(1), pp.20~24 (1997)
- Zou J, "Antisense inhibition of ATM gene enhances the radiosensitivity of head and neck squamous cell carcinoma in mice", J Exp Clin Cancer Res, 27, pp.56~ (2008)
- Ciardiello F, "Antitumor activity of sequential treatment with topotecan and anti-epidermal growth factor receptor monoclonal antibody C225", Clin Cancer Res, 5(4), pp.909~916 (1999)
- Adrian TE, "Novel marine-derived anti-cancer agents", Curr Pharm Des., 13(33), pp.3417~3426 (2007)
- Jeong SY, "Cytotoxicity and apoptosis induction of Bacillus vallismortis BIT-33 metabolites on colon cancer carcinoma cells", J Appl Microbiol, 104(3), pp.796~807 (2008)
- Lim YC, "Growth inhibition and apoptosis by(-)-epicatechin gallate are mediated by cyclin D1 suppression in head and neck squamous carcinoma cells", Eur J Cancer, 42(18), pp.3260~3266 (2006)
- Los M, "The role of caspases in development,immunity,and apoptotic signal transduction:lessons from knockout mice", Immunity, 10(6), pp.629~639 (1999)
- Thornberry NA, "A combinatorial approach defines specificities of members of the caspase family and granzyme B.",Functional relationships established for key mediators of apoptosis", J Biol Chem, 272(29), pp.17907~17911 (1997)
- Rano TA, "A combinatorial approach for determining protease specificities:application to interleukin-1beta converting enzyme(ICE)", Chem Biol, 4(2), pp.149~155 (1997)
- Schultz DR, "Apoptosis:programmed cell death at a molecular level", Semin Arthritis Rheum, 32(6), pp.345~369 (2003)
- Bode AM, "Post-translational modification of p53 in tumorigenesis", Nat Rev Cancer, 4(10), pp.793~805 (2004)
- Ritta M, "Cell cycle and viral and immunologic profiles of head and neck squamous cell carcinoma as predictable variables of tumor progression", Head Neck, 31(3), pp.318~327 (2009)
- Gurnani M, "Adenovirus-mediated p53 gene therapy has greater efficacy when combined with chemotherapy against human head and neck,ovarian,prostate,and breast cancer", Cancer Chemother Pharmacol., 44(2), pp.143~151 (1999)
- Rosenthal DI, "Prevention and treatment of dysphagia and aspiration after chemoradiation for head and neck cancer", J Clin Oncol, 24(17), pp.2636~2643 (2006)
- Beis D, "In vivo cell biology:following the zebrafish trend", Trends Cell Biol, 16(2), pp.105~112 (2006)
- den Hertog J, "Chemical genetics: Drug screens in Zebrafish", Biosci Rep, 25(5-6), pp.289~297 (2005)
- Mandrekar N, "Significance of the zebrafish model in the discovery of bioactive molecules from nature", Biotechnol Lett, 31(2), pp.171~179 (2009)