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Altered Expressions of PTEN, p53, Bax and Bcl-2 Genes by a Bioactive Pigment from Streptomyces sp. JUA14 Mediate Apoptosis of Cancer Cells

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Abstract

Cancer is one of the leading causes of death around the world with major side effects for existing therapies. The current study was aimed to extract pigments from microbial isolates and evaluate their efficacy and anticancer mechanisms. Pigment from a selected microbial isolate was extracted using methanol and its cytotoxicity was assessed on cancer cells by 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide assay. Promising isolate was identified by molecular methods and purified by TLC. The apoptotic potential of the purified pigment was analysed by trypan blue, caspase and nitrite assays, LDH cytotoxicity, flow cytometry of cell cycle and gene expression studies (RT-qPCR) on cancer cell lines and healthy lymphocytes. The yellow pigment, B3, extracted from the isolate Streptomyces sp. JUA14 has exhibited promising anticancer activity as shown by increased caspase and LDH activities, nitrite levels, G1 phase arrest in cell cycle, and enhanced p53, PTEN, Bax and down-regulated Bcl-2 expressions in the cancer cells which indicated the apoptotic potential of the pigment. The normal lymphocyte cells remained unaffected and the in vivo acute toxicity studies were supportive of the non-toxic nature of the compound in Balb/c mice. Using GC-MS method, pigment characterization revealed the presence of marmycin A and streptazon C which were antitumor compounds reported earlier. The pigment B3 from Streptomyces sp. JUA14 has potent anticancer effects being non-toxic to the healthy cells and hence shows promise towards future characterization and in vivo efficacy studies.

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REFERENCES

  1. Ashrafizadeh, M., Zarrabi, A., Hushmandi, K., Hashemi, F., Rahmani Moghadam, E., et al., ACS Comb. Sci., 2020, vol. 22, no. 12, pp. 669–700.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Taylor, M.W., Radax, R., Steger, D., and Wagner, M., Microbiol. Mol. Biol. Rev., 2007, vol. 71, no. 2, pp. 295–347.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Qian, P.Y., Xu, Y., and Fusetani, N., Biofouling, 2009, vol. 26, no. 2, pp. 223–234.

    Article  Google Scholar 

  4. Narsing Rao, M.P., Xiao, M., and Li, W.J., Front. Microbiol., 2017, vol. 8, p. 1113.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Ventura, M., Canchaya, C., Tauch, A., Chandra, G., Fitzgerald, G.F., Chater, K.F., and van Sinderen, D., Microbiol. Mol. Biol. Rev., 2007, vol. 71, no. 3, pp. 495–548.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. McCarthy, A.J. and Williams, S.T., Gene, 1992, vol. 115, nos. 1–2, pp. 189–192.

    Article  CAS  PubMed  Google Scholar 

  7. Berdy, J., J. Antibiot., 2005, vol. 58, no. 1, pp. 1–26.

    Article  CAS  Google Scholar 

  8. Mackay, S.J., Appl. Environ. Microbiol., 1977, vol. 33, no. 2, pp. 227–230.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Shirling, E.B. and Gottlieb, D., Int. J. Syst. Bacteriol., 1964, pp. 1–27.

  10. Mathur, R. and Swaminathan, S., Ind. J. Med. Res., 2018, vol. 148, no. 3, p. 279.

    Article  Google Scholar 

  11. Mossmann, T., J. Immunol. Methods, 1983, vol. 65, pp. 49–53.

    Article  Google Scholar 

  12. Kirchner, J.G., Miller, J.M., and Keller, G.J., Anal. Chem., 1951, vol. 23, no. 3, pp. 420–425.

    Article  CAS  Google Scholar 

  13. Ian, R. and Freshney, R., Culture of Animal Cells: A Manual of Basic Technique, Wiley, 2005, pp. 43–51.

    Google Scholar 

  14. Brousseau, P., Pellerin, J., Morin, Y., Cyr, D., Blakley, B., Boermans, H., and Fournier, M., Toxicology, 1999, vol. 142, no. 2, pp. 145–156.

    Article  Google Scholar 

  15. Weyermann, J., Lochmann, D., and Zimmer, A., Int. J. Pharm., 2005, vol. 288, no. 2, pp. 369–376.

    Article  CAS  PubMed  Google Scholar 

  16. Philchenkov, A., J. Cell. Mol. Med., 2004, vol. 8, no. 4, pp. 432–444.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Venkatachalam, P. and Nadumane, V.K., Mycology, 2021, vol. 12, no. 2, pp. 69–81.

    Article  CAS  Google Scholar 

  18. Ding, A.H., Nathan, C.F., and Stuehr, D.J., J. Immunol., 1988, vol. 141, no. 7, pp. 2407–2412.

    Article  CAS  PubMed  Google Scholar 

  19. Gohlke, B.O., Nickel, J., Otto, R., Dunkel, M., and Preissner, R., Nucleic Acids Res., 2016, vol. 44, no. D1, pp. D932–D937.

    Article  CAS  PubMed  Google Scholar 

  20. El, Allaoui, A., Filali, F.R., Oumokhtar, B., and Ibijbijen, J., La Science. En. Liberté, 2011, vol. 3, pp. 1–15.

    Google Scholar 

  21. Strober, W., Fuss, I.J., and Blumberg, R.S., Annu. Rev. Immunol., 2002, vol. 20, p. 495.

    Article  CAS  PubMed  Google Scholar 

  22. Martin, G.D., Tan, L.T., Jensen, P.R., Dimayuga, R.E., Fairchild, C.R., Raventos-Suarez, C., and Fenical, W., J. Nat. Prod., 2007, vol. 70, no. 9, pp. 1406–1409.

    Article  CAS  PubMed  Google Scholar 

  23. Puder, C., Krastel, P., and Zeeck, A., J. Nat. Prod., 2000, vol. 63, no. 9, pp. 1258–1260.

    Article  CAS  PubMed  Google Scholar 

  24. Camerino, B. and Palamidessi, G., Gazz. Chim. Ital., 1960, vol. 90, pp. 1802–1815.

    Google Scholar 

  25. Burger, S.R., and Bennett, J.W., Appl. Environ. Microbiol., 1985, vol. 50, no. 2, pp. 487–490.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Li, F., Maskey, R.P., Qin, S., Sattler, I., Fiebig, H.H., Maier, A., Zeeck, A., and Laatsch, H., J. Nat. Prod., 2005, vol. 68, no. 3, pp. 349–353.

    Article  CAS  PubMed  Google Scholar 

  27. Harvey, N.L. and Kumar, S., Apoptosis, 1998, pp. 107–128.

  28. Korde, A., Choudhari, S., Chaudhary, M., Bagde, S., Gadbail, A.R., and Joshi, T., World J. Surg. Oncol., 2013, vol. 11, no. 1, pp. 1–11.

    Article  Google Scholar 

  29. Tschugguel, W., Schneeberger, C., Unfried, G., Czerwenka, K., Weninger, W., Mildner, M., et al., Breast. Cancer. Res. Treat., 1999, vol. 56, no. 2, pp. 143–149.

    Article  Google Scholar 

  30. Alalami, O. and Martin, J.H.J., Cancer Lett., 1998, vol. 123, no. 1, pp. 99–105.

    Article  CAS  PubMed  Google Scholar 

  31. Puder, C., Krastel, P., and Zeeck, A., J. Nat. Prod., 2000, vol. 63, no. 9, pp. 1258–1260.

    Article  CAS  PubMed  Google Scholar 

  32. Martin, G.D., Tan, L.T., Jensen, P.R., Dimayuga, R.E., Fairchild, C.R., Raventos-Suarez, C., and Fenical, W., J. Nat. Prod., 2007, vol. 70, no. 9, pp. 1406–1409.

    Article  CAS  PubMed  Google Scholar 

  33. Ukwuani, A.N., Abubakar, M.G., Hassan, S.W., Agaie, B.M., Int. J. Pharm. Sci. Drug. Res., 2012, vol. 4, no. 4, pp. 245–249.

    Google Scholar 

  34. Olson, H., Betton, G., Robinson, D., Thomas, K., Monro, A., Kolaja, G., et al., Regul. Toxicol. Pharmacol., 2000, vol. 32, no. 1, pp. 56–67.

    Article  CAS  PubMed  Google Scholar 

  35. Olorunnisola, O.S., Bradley, G., and Afolayan, A.J., Afr. J. Biotechnol., 2012, vol. 11, no. 83, pp. 14934–14940.

    Article  Google Scholar 

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ACKNOWLEDGMENTS

The authors thank Jain University, Bangalore, India for providing the infrastructural support. The authors would like to thank Dr. S. Kumar, IAH&VB, Bangalore and Dr. S. Rani, IAH&VB, Bangalore for providing the qRT-PCR facility. The authors would also like to thank Geniron Biolabs, Anekal, Bangalore for permitting to carry out the in vivo mice model experiments.

Funding

This work was supported by Department of Science and Technology- Science and Engineering Board (DST-SERB), Government of India.

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  1. Department of Biotechnology, School of Sciences, JAIN (Deemed to be University), Bangalore, India

    B. Gajaraj & V. K. Nadumane

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  1. B. Gajaraj
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  2. V. K. Nadumane
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Correspondence to V. K. Nadumane.

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The authors declare that they have no conflicts of interest that are relevant to the content of this article. This article does not contain any studies involving animals or human participants performed by any of the authors.

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Gajaraj, B., Nadumane, V.K. Altered Expressions of PTEN, p53, Bax and Bcl-2 Genes by a Bioactive Pigment from Streptomyces sp. JUA14 Mediate Apoptosis of Cancer Cells. Appl Biochem Microbiol 59, 145–159 (2023). https://doi.org/10.1134/S0003683823020059

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