J Appl Biomed 13:199-212, 2015 | DOI: 10.1016/j.jab.2015.04.001

Anticancer potential of bioactive 16-methylheptadecanoic acid methyl ester derived from marine Trichoderma

Kandasamy Saravanakumara,b, Raju Vivekc, Natarajan Sithranga Boopathyb, Li Yaqiana, Kandasamy Kathiresanb, Jie Chena,*
a Department of Environmental Resources, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, PR China
b Center of Advanced Study in Marine Biology, Faculty of Marine Sciences, Annamalai University, Parangipettai, India
c Department of Biomedical Engineering, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, PR China

The present work aimed at purifying the intracellular fungal metabolites, such as 16-methylheptadecanoic acid methyl ester (HDA) and 9,12-octadecadienoic acid (ODA) from marine Trichoderma, Hypocrea lixii TSK8, Hypocrea rufa SKS2 respectively, and investigating their anticancer and antioxidant effects. The two fungal metabolites were tested against two human cancer cell lines, namely oral cancer (KB) and skin carcinoma (A431) by using MTT assay. The inhibitory concentrations (IC50) against KB oral cancer cells were found to be 18.75 ± 0.12 μg/mL for HDA and 75.50 ± 0.42 μg/mL for ODA. Whereas IC50 values of HDA and ODA against A431 were found 37.5 ± 0.42 μg/mL and 72.89 ± 0.15 μg/mL, respectively. In addition, the down-regulation of heat shock protein 90 kDa (HSP90) was confirmed by using SDS-PAGE and Western blot analysis. The effect of HDA induced apoptosis via ROS-dependent internucleosomal DNA fragmentation was confirmed by AGE analysis. We further evaluated the in vivo anti-skin cancer activity of HDA in Swiss albino mice induced with skin cancer by 7,12-dimethylbenz(a)anthracene (DMBA) and croton oil (CO). The in vivo hematological, biochemical and histopathological results revealed that the fungal metabolite HDA was a highly potent anticancer compound against the skin cancer.

Keywords: Marine Trichoderma; Heptadecanoic acid; ROS; HSP90; Apoptosis

Received: November 5, 2014; Revised: April 1, 2015; Accepted: April 9, 2015; Published: July 1, 2015  Show citation

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Saravanakumar K, Vivek R, Boopathy NS, Yaqian L, Kathiresan K, Chen J. Anticancer potential of bioactive 16-methylheptadecanoic acid methyl ester derived from marine Trichoderma. J Appl Biomed. 2015;13(3):199-212. doi: 10.1016/j.jab.2015.04.001.
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References

  1. Ande, S.R., Fussi, H., Knauer, H., Murkovic, M., Ghisla, S., Frohlich, K.U., Macheroux, P., 2008. Induction of apoptosis in yeast by L-amino acid oxidase from the Malayan pit viper Calloselasma rhodostoma. Yeast 25, 349-357. Go to original source... Go to PubMed...
  2. Armstrong, B.K., Kricker, A., 2001. The epidemiology of UV induced skin cancer. J. Photochem. Photobiol. B: Biol. 63, 8-18. Go to original source... Go to PubMed...
  3. Berger, J., 2011. The age of biomedicine: current trends in traditional subjects. J. Appl. Biomed. 9, 57-61. Go to original source...
  4. Branislav, R., Marijana, M.R., Kosanic, T.P., 2011. Antioxidant, antimicrobial and anticancer activity of the lichens Cladonia furcata, Lecanora atra and Lecanora muralis. BMC Comp. Altern. Med. 11 97 pp. Go to original source... Go to PubMed...
  5. Chaverri, P., Samuels, G.J., 2003. Mycologia 95, 11-19. Go to original source... Go to PubMed...
  6. Cheng, C.H., Yang, C.A., Liu, S.Y., Lo, C.T., Huang, H.C., Liao, F.C., Peng, K.C., 2011. Cloning of a novel L-amino acid oxidase from Trichoderma harzianum ETS 323 and bioactivity analysis of overexpressed L-amino acid oxidase. J. Agric. Food Chem. 59, 9142-9149. Go to original source... Go to PubMed...
  7. Cibin, T.R., Gayathri Devi, D., Abraham, A., 2011. Chemoprevention of two-stage skin cancer in vivo by Saraca asoca. Integr. Cancer Ther. 11 (3), 279-286. Go to original source... Go to PubMed...
  8. Ciscotto, P., Machado, R.A., de Avila, E.A., Coelho, J., Oliveira, C. G., Farais, L.M., de Carvalho, M.A., Maria, W.S., Sanchez, E.F., Borges, A., Chavez-Olortegui, C., 2009. Antigenic microbial and parasitic properties of an L-amino acid oxidase isolated from Bothrops jararaca snake venom. Toxicon 53, 330-341. Go to original source... Go to PubMed...
  9. Druzhinina, I.S., Seidl-Seiboth, V., Herrera-Estrella, A., Horwitz, B.A., Kenerley, C.M., Monte, E., Mukherjee, P.K., Zeilinger, S., Grigoriev, I.V., Kubicek, C.P., 2011. Trichoderma: the genomics of opportunistic success. Nat. Rev. Microbiol. 16, 749-759. Go to original source... Go to PubMed...
  10. Duan, X.J., Zhang, W.W., Li, X.M., Wang, B.G., 2006. Evaluation of antioxidant property of extract and fractions obtained from a red alga Polysiphonia urceolata. Food Chem. 95, 37-43. Go to original source...
  11. Folmer, E., Berends, W., Luttighuis, O.P., Hillegersberg, V.J., 2009. Top IS research on quality of transaction standards, a structured literature review to identify a research gap. In: Paper presented at the 6th International Conference on Standardization and Innovation in Information Technology, Tokyo, Japan.
  12. Franco, M.C., Yaozu, Y., Refakis, C.A., Feldman, J.L., Stokes, A.L., Basso, M., Melero Fernándezde Mera, R.M., Sparrow, N.A., Calingasan, N.Y., Kiaei, M., Rhoads, T.W., Ma, T.C., Grumet, M., Barnes, S., Beal, M.F., Beckman, J.S., Mehl, R., Estévez, A. G., 2013. Nitration of Hsp90 induces cell death. Proc. Natl. Acad. Sci. U.S.A., http://dx.doi.org/10.1073/PNAS.1215177110. Go to original source... Go to PubMed...
  13. Garo, E., Starks, C.M., Jensen, P.R., Fenical, W., Lobkovsky, E., Clardy, J., 2003. Trichodermamides A and B, cytotoxic modified dipeptides from the marine derived fungus Trichoderma virens. J. Nat. Prod. 66, 423-426. Go to original source... Go to PubMed...
  14. Govindarajan, R., Rastogi, S., Vijayakumar, M., Rawat, A.K.S., Shirwaikar, A., Mehrotra, S., Pushpangadam, P., 2003. Studies on antioxidant activities of Desmodium gangetium. Biol. Pharm. Bull. 26, 1424-1427. Go to original source... Go to PubMed...
  15. Gulcin, I., Sat, I.G., Beydemi, S., Kufrevioglu, O.I., 2004. Evaluation of the in vitro antioxidant properties of extracts of Broccoli Brassica oleraceal. Ind. J. Food Sci. 16, 17-30.
  16. Henk, M., Laszig, R., Rube, C., Schafer, U., Schilcher, H., Mose, K. D., Beer, B.S., Burger, K.T., Dougherty, U., Frommhold, C.H., 2003. Erythropoietin to treat head and neck cancer patients with anaemia undergoing radiotherapy: randomized doubleblind, placebo-controlled trial. Lancet 362, 1255-1260. Go to original source... Go to PubMed...
  17. Holmstrom, K.M., Finkel, T., 2014. Cellular mechanisms and physiological consequences of redox-dependent signalling. Nat. Rev. Mol. Cell Biol. 15, 411-421. Go to original source... Go to PubMed...
  18. Jaklitsch, W.M., Samuels, G.J., 2006. Stud. Mycol. 56 156 pp. Go to original source...
  19. Kim, D.O., Lee, K.W., Lee, H.J., Lee, C.Y., 2002. Vitamin C equivalent antioxidant capacity (VCEAC) of phenolic phytochemicals. J. Agric. Food Chem. 50, 3713-3717. Go to original source... Go to PubMed...
  20. Kim, E.K., Kim, Y.S., Lee, S.J., Jeon, Y.J., Lee, J.D., Son, T.I., Ahn, C. B., Kim, Y.T., Moon, S.H., Jeon, B.T., Kim, S.W., Park, P.J., 2010. Anticancer effect of lipids partially purified from Pacific oyster, Crassostrea gigas on PC3 cells. Food Sci. Biotechnol. 19 (1), 213-217. Go to original source...
  21. King, J., 1965. Practical clinical enzymology. Van Nostrand Company Ltd., London83-208.
  22. Kryston, T.B., Georgiev, A.B., Pissis, P., Georgakilas, A.G., 2011. Role of oxidative stress and DNA damage in human carcinogenesis. Mutat. Res. Fundam. Mol. Mech. Mutagen. 711, 193-201. Go to original source... Go to PubMed...
  23. Liu, S.Y., Lo, C.T., Shibu, M.A., Leu, Y.L., Jen, B.Y., Peng, K.C., 2009. Study on the anthraquinones separated from the cultivation of Trichoderma harzianum strain Th-R16 and their biological activity. J. Agric. Food Chem. 57, 7288-7292. Go to original source... Go to PubMed...
  24. Lu, Q.M., Wei, Q., Jin, Y., Wei, J.F., Wang, W.Y., Xiong, Y.L., 2002. L-amino acid oxidase from Trimeresurus jerdonii snake venom: purification, characterization, platelet aggregation-inducing and antibacterial effects. J. Nat. Toxins 11, 345-352.
  25. Martins, M.P., Mouad, A.M., Boschini, L., Seleghim, M.H.R., Sette, L.D., Meleiro Porto, A.L., 2011. Marine fungi Aspergillus sydowii and Trichoderma sp. catalyze the hydrolysis of benzyl glycidyl ether. Mar. Biotechnol. 13, 314-320. Go to original source... Go to PubMed...
  26. Mason, P., 1999. Central mechanism of pain modulation. Curr. Opin. Neurobiol. 9, 436-441. Go to original source... Go to PubMed...
  27. Masuma, R., Yamaguchi, Y., Noumi, M., Omura, S., Namikosh, M., 2001. Effect of sea water concentration on hyphal growth and antimicrobial metabolite production in marine fungi. MycoScience 42, 455-459. Go to original source...
  28. Miguel, A.H., Edgardo, U.E.N., Artemio, M.M., Stewart, A., Alfredo, H.H.E., 2012. Proc. Natl. Acad. Sci. U.S.A. 109 (37), 14918-14923. Go to original source... Go to PubMed...
  29. Norrheim, L., Sorensen, H., Gautvik, K., Bremer, J., Spydevold, O., 1990. Synergistic actions of tetradecylthioacetic acid (TTA) and dexamethasone on induction of the peroxisomal boxidation and on growth inhibition of Morris hepatoma cells: both effects are counteracted by insulin. Biochim. Biophys. Acta 1051, 319-323. Go to original source... Go to PubMed...
  30. Oyaizu, M., 1986. Studies on product of browning reaction prepared from glucose amine. Jpn. J. Nutr. 44, 307-315. Go to original source...
  31. Prieto, P., Pineda, M., Aguilar, M., 1999. Spectrophotometric quantitation of antioxidant capacity through the formation of a phospho molybdenum complex: specific application to the determination of vitamin E. Anal. Biochem. 269, 337-341. Go to original source... Go to PubMed...
  32. Quinlan, R.A., Ellis, R.J., 2013. Chaperones: needed for both the good times and the bad times. Philos. Trans. B 368, http://dx.doi.org/10.1098/rstb.2013.0091. Go to original source... Go to PubMed...
  33. Ruiz, N., Dubois, N., Wielgosz, C., Robiou, P.T., Berge, E.P., Pouchus, Y.F., Barnathan, G., 2007. Lipid content and fatty acid composition of a marine-derived Trichoderma longibrachiatum strain cultured by agar surface and submerged fermentations. Process Biochem. 42, 676-680. Go to original source...
  34. Saravanakumar, K., Shanmuga Arasu, V., Kathiresan, K., 2013. Effect of Trichoderma on soil phosphate solubilization and growth improvement of Avicennia marina. Aquat. Bot. 104, 101-105. Go to original source...
  35. Saravanakumar, K., Sahu, S.K., Kathiresan, K., 2012. In silico studies on fungal metabolite against skin cancer protein (4,5diarylisoxazole HSP90 chaperone). ISRN Dermatol. 5, http://dx.doi.org/10.5402/2012/626214. Go to original source... Go to PubMed...
  36. Sawarkar, R., Sievers, C., Paro, R., 2012. Hsp90 globally targets paused RNA polymerase to regulate gene expression in response to environmental stimuli. Cell 149, 807-818. Go to original source... Go to PubMed...
  37. Shibu, M.A., Lin, H.S., Yang, H.H., Peng, K.C., 2012. Trichoderma harzianum ETS 323-mediated resistance in Brassica oleracea var. capitata to Rhizoctonia solani involves the novel expression of a glutathione S-transferase and a deoxycytidine deaminase. J. Agric. Food Chem. 60, 10723-10732. Go to original source... Go to PubMed...
  38. Sithranga Boopathy, N., Kathiresan, K., 2010. Anticancer drugs from marine flora: an overview. J. Oncol. 18 pp. Go to original source... Go to PubMed...
  39. Sithranga Boopathya, N., Kathiresana, K., Jeonb, Y.J., 2011. Effect of mangrove black tea extract from Ceriops decandra (Griff.) on hematology and biochemical changes in dimethyl benz[a] anthracene-induced hamster buccal pouch carcinogenesis. Environ. Toxicol. Pharmacol. 32, 193-200. Go to original source... Go to PubMed...
  40. Slingleton, V.L., Slinkard, K., 1997. Total phenolic analyses: automation and comparison with manual method. Am. J. Enol. Viticult. 28, 49-55. Go to original source...
  41. Staples, M.P., Elwood, M., Burton, R.C., Williams, J.L., Marks, R., Giles, G.G., 2006. Non-melanoma skin cancer in Australia: the 2002 national survey and trends since 1985. Med. J. Aust. 184, 6-10. Go to original source... Go to PubMed...
  42. Steele, V.E., Lubet, R.A., 2010. The use of animal models for cancer chemoprevention drug development. Semin. Oncol. 37 (4), 327-338. Go to original source... Go to PubMed...
  43. Sun, Y., Tian, L., Huang, J., Ma, H.Y., Zheng, Z., Yasukawa, K., Pei, Y.H., 2008. Novel polyketides from the marine-derived fungus Trichoderma reesei. Oncol. Lett. 10 (3), 393-396. Go to original source... Go to PubMed...
  44. Thakur, N.L., Hentschel, U., Krasko, A., Pabel, C.T., Anr, A.C., Muller, W.E.G., 2003. Antibacterial activity of the sponge Suberites domuncula and its primmorphs: potential basis for epibacterial chemical defense. Aquat. Microbial Ecol. 31, 77-83. Go to original source...
  45. Thangam, R., Senthilkumar, D., Suresh, V., Sathuvan, M., Sivasubramanian, S., Pazhanichamy, K., Gorlagunta, P.K., Kannan, S., Gunasekaran, P., Rengasamy, R., Sivaraman, J., 2014. Induction of ROS-dependent mitochondria-mediated intrinsic apoptosis in MDA-MB-231 cells by glycoprotein from codium decorticatum. J. Agric. Food Chem. 62, 3410-3421. Go to original source... Go to PubMed...
  46. Trepel, J., Mollapour, M., Giaccone, G., Neckers, L., 2010. Targeting the dynamic HSP90 complex in cancer. Nat. Rev. Cancer 10, 537-549. Go to original source... Go to PubMed...
  47. Unger, F.T., Witte, I., David, K.A., 2015. Prediction of individual response to anticancer therapy: historical and future perspectives. Cell. Mol. Life Sci. 72, 729-757. Go to original source... Go to PubMed...
  48. Vivek, R., Thangam, R., Nipun, B.V., Rejeeth, C., Sivasubramanian, S., Gunasekaran, P., Muthuchelian, K., Kannan, S., 2014. Multifunctional HER2-antibody conjugated polymeric nanocarrier-based drug delivery system for multidrug-resistant breast cancer therapy. ACS Appl. Mater. Interfaces 6469-6480. Go to original source...
  49. Wang, S., Konorev, E.A., Kotamraju, S., Joseph, J., Kalivendi, S., Kalyanaraman, B., 2004. Doxorubicin induces apoptosis in normal and tumor cells via distinctly different mechanismsintermediacy of H2O2 and p53-dependent pathways. J. Biol. Chem. 279 (24), 25535-25543. Go to original source... Go to PubMed...