Toxicological Evaluation of Occidiofungin against Mice and Human Cancer Cell Lines


Occidiofungin, a glyco-lipopeptide obtained from the liquid culture of Burkholderia contaminans MS14, has been identified as a novel fungicide. The natural product was shown to have a minimal amount of toxicity in a previous mouse toxicity study following intraperitoneal and subcutaneous administration. In this study, the toxicity of occidiofungin was evaluated following a 5 mg/kg intravenous tail vein injection. In addition, the toxicity of occidiofungin was evaluated against human fibroblast and cancer cell lines. Weight loss was the most significant observation following intravenous administration of occidiofungin. Histology, hematology, and blood serum chemistry did not reveal any significant signs of toxicity. The activity observed in the in vitro cytotoxicity assay against the cancer cell lines was all below 75 nM concentration of occidiofungin. To date, the potency of occidiofungin against these cancer cell lines is greater than any activity observed against fungi. The findings in this study support the need to further evaluate occidiofungin’s chemotherapeutic potential.

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Hing, S. , Ravichandran, A. , Escano, J. , Cooley, J. , Austin, F. , Lu, S. , Pruett, S. and Smith, L. (2014) Toxicological Evaluation of Occidiofungin against Mice and Human Cancer Cell Lines. Pharmacology & Pharmacy, 5, 1085-1093. doi: 10.4236/pp.2014.511118.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Ellis, D., Gosai, J., Emrick, C., Heintz, R., Romans, L., Gordon, D., Lu, S., Austin, F. and Smith, L. (2012) Occidiofungin’s Chemical Stability and in Vitro Potency against Candida species. Antimicrob Agents Chemother, 56, 765-769.
[2] Emrick, D., Ravichandran, A., Gosai, J., Lu, S., Gordon, D.M. and Smith, L. (2013) The Antifungal Occidiofungin Triggers an Apoptotic Mechanism of Cell Death in Yeast. Journal of Natural Products, 76, 829-838.
[3] Gu, G., Lu, S. and Wang, N. (2008) AmbR1 and AmbR2 Are Two Transcriptional Regulators Essential for the Antifungal Activity of Burkholderia sp Strain MS14. Phytopathology, 98, S63-S63.
[4] Gu, G., Smith, L., Liu, A. and Lu, S.-E. (2011) A genetic and Biochemical Map for the Biosynthesis of Occidiofungin, an Antifungal Produced by Burkholderia contaminans Strain MS14. Applied and Environmental Microbiology, 77, 6189-6198.
[5] Gu, G., Wang, N., Chaney, N., Smith, L. and Lu, S.-E. (2009) AmbR1 is a Key Transcriptional Regulator for Production of Antifungal Activity of Burkholderia contaminans Strain MS14. FEMS Microbiology Letters, 297, 54-60.
[6] Gu, G. Y., Smith, L., Wang, N., Wang, H. and Lu, S.E. (2009) Biosynthesis of an Antifungal Oligopeptide in Burkholderia contaminans Strain MS14. Biochemical and Biophysical Research Communications, 380, 328-332.
[7] Lu, S.-E., Novak, J., Austin, F. W., Gu, G., Ellis, D., Kirk, M., Wilson-Stanford, S., Tonelli, M. and Smith, L. (2009) Occidiofungin, a Unique Antifungal Glycopeptide Produced by a Strain of Burkholderia contaminans. Biochemistry, 48, 8312.
[8] Ravichandran, A., Gu, G., Escano, J., Lu, S.-E. and Smith, L. (2013) The Presence of Two Cyclase Thioesterases Expands the Conformational Freedom of the Cyclic Peptide Occidiofungin. Journal of Natural Products, 76, 150-156.
[9] Clancy, C.J., Huang, H., Cheng, S., Derendorf, H. and Nguyen, M.H. (2006) Characterizing the Effects of Caspofungin on Candida albicans, Candida parapsilosis and Candida glabrata Isolates by Simultaneous Time-Kill and Postantifungal-Effect Experiments. Antimicrobial Agents and Chemotherapy, 50, 2569-2572.
[10] Ernst, E.J., Klepser, M.E. and Pfaller, M.A. (2000) Postantifungal Effects of Echinocandin, Azole, and Polyene Antifungal Agents against Candida albicans and Cryptococcus neoformans. Antimicrobial Agents and Chemotherapy, 44, 1108-1111.
[11] Wei, T., Cooley, J., Austin, F., Lu, S., Smith, L. and Pruett, S. (2012) Nonclinical Toxicological Evaluation of Occidiofungin, a Unique Glycolipopeptide Antifungal. International Journal of Toxicology, 31, 326-336.
[12] Luster, M.I., Portier, C., Pait, D.G., White Jr., K.L., Gennings, C., Munson, A.E. and Rosenthal, G.J. (1992) Risk Assessment in Immunotoxicology I. Sensitivity and Predictability of Immune Tests. Fundamental and Applied Toxicology: Official Journal of the Society of Toxicology, 18, 200-210.
[13] Loftsson, T. and Brewster, M.E. (2012) Cyclodextrins as Functional Excipients: Methods to Enhance Complexation Efficiency. Journal of Pharmaceutical Sciences, 101, 3019-3032.
[14] Germolec, D.R., Kashon, M., Nyska, A., Kuper, C.F., Portier, C., Kommineni, C., Johnson, K.A. and Luster, M.I. (2004) The Accuracy of Extended Histopathology to Detect Immunotoxic Chemicals. Toxicological Sciences: An Official Journal of the Society of Toxicology, 82, 504-514.
[15] Gabay, C., Ben-Bassat, H., Schlesinger, M. and Laskov, R. (1999) Somatic Mutations and Intraclonal Variations in the Rearranged Vκ Genes of B-Non-Hodgkin’s Lymphoma Cell Lines. European Journal of Haematology, 63, 180-191.
[16] Hamilton, T.C., Young, R.C. and Ozols, R.F. (1984) Experimental Model Systems of Ovarian Cancer: Applications to the Design and Evaluation of New Treatment Ap-proaches. Seminars in Oncology, 11, 285-298.
[17] Wright, W.C., Daniels, W.P. and Fogh, J. (1981) Distinction of Seventy-One Cultured Human Tumor Cell Lines by Polymorphic Enzyme Analysis. Journal of the National Cancer Institute, 66, 239-247.
[18] Roccaro, A.M., Hideshima, T., Richardson, P.G., Russo, D., Ribatti, D., Vacca, A., Dammacco, F. and Anderson, K.C. (2006) Bortezomib as an Antitumor Agent. Current Pharmaceutical Biotechnology, 7, 441-448.
[19] Tobinai, K. (2007) Proteasome Inhibitor, Bortezomib, for Myeloma and Lymphoma. International Journal of Clinical Oncology, 12, 318-326.
[20] Cavo, M. (2006) Proteasome Inhibitor Bortezomib for the Treatment of Multiple Myeloma. Leukemia, 20, 1341-1352.
[21] Chauhan, D., Hideshima, T., Mitsiades, C., Richardson, P. and Anderson, K.C. (2005) Proteasome Inhibitor Therapy in Multiple Myeloma. Molecular Cancer Therapeutics, 4, 686-692.
[22] Anderson, K.C. (2004) Bortezomib Therapy for Myeloma. Current Hematology Reports, 3, 65-65.
[23] Anderson, K.C. (2007) Targeted Therapy of Multiple Myeloma Based upon Tumor-Microenvironmental Interactions. Experimental Hematology, 35, 155-162.
[24] Adams, J., Palombella, V.J., Sausville, E.A., Johnson, J., Destree, A., Lazarus, D.D., Maas, J., Pien, C.S., Prakash, S. and Elliott, P.J. (1999) Proteasome Inhibitors: A Novel Class of Potent and Effective Antitumor Agents. Cancer Research, 59, 2615-2622.
[25] Fuchs, B.A. and Pruett, S.B. (1993) Morphine Induces Apoptosis in Murine Thymocytes in Vivo but Not in Vitro: Involvement of both Opiate and Glucocorticoid Receptors. The Journal of Pharmacology and Experimental Therapeutics, 266, 417-423.
[26] Demain, A.L. and Vaishnav, P. (2011) Natural Products for Cancer Chemotherapy. Microbial Biotechnology, 4, 687-699.

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