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Abstract

The Philippine archipelago is rich in marine biodiversity and resources that are widely unexplored. Its marine sediments harbor marine microbes that possess secondary metabolites with potent bioactivities. This study aims to determine the antiproliferative activity of the crude extracts of selected Actinomycete isolates (DSD011, DSD017, and DSD042) from Islas de Gigantes, Carles, Iloilo. The antiproliferative screening was done using Saccharomyces cerevisiae as a model organism. Crude extracts of isolates that are active in inhibiting the growth of S. cerevisiae were determined using the broth microdilution method. Afterward, the active extract was tested using antiproliferative and budding yeast assays. With the antiproliferative model, only DSD011 was found to inhibit the growth of S. cerevisiae. The percentage of live and dead cells in DSD011 was comparable to those treated with Triton X (positive control). Further, the budding yeast analysis showed that DSD011 induced G1 cell cycle arrest of nearly 50% of S. cerevisiae cells. Thus, DSD011, a marine sediment-derived Actinomycete, serves as a potential source of naturally occurring bioactive compounds with antiproliferative properties.

References

Akram, Z., Ahmed, I., Mack, H., Kaur, R., Silva, R.C., Castilho, B.A., ... & Munn, A.L. (2020). Yeast as a model to understand actin-mediated cellular functions in mammals—illustrated with four actin cytoskeleton proteins. Cells, 9(3), 672.

Armstrong, C.A., & Tomita, K. (2017). Fundamental mechanisms of telomerase action in yeasts and mammals: understanding telomeres and telomerase in cancer cells. Open Biology, 7(3), 160338.

Asati, V., Mahapatra, D.K., & Bharti, S.K. (2014) Thiazolidine-2, 4-diones as multi-targeted scaffold in medicinal chemistry: potential anticancer agents. European Journal of Medicinal Chemistry, 87, 814-833.

Bertoli, C., Skotheim, J.M., & De Bruin, R.A. (2013). Control of cell cycle transcription during G1 and S phases. Nature Reviews Molecular Cell Biology, 14(8), 518-528.

Blunt, J.W., Copp, B.R., Munro, M., Northcote, P.T., & Prinsep, M.R. (2013) Marine natural products. Natural Product Reports, 28:196-268.

Boonkaewwan, C., & Burodom, A. (2013). Anti‐inflammatory and immunomodulatory activities of stevioside and steviol on colonic epithelial cells. Journal of the Science of Food and Agriculture, 93(15), 3820-3825.

Brucoli, F., Natoli, A., Marimuthu, P., Borrello, M.T., Stapleton, P., Gibbons, S., & Schńtzlein, A. (2012) Efficient synthesis and biological evaluation of proximicins A, B and C. Bioorganic & Medicinal Chemistry, 20, 2019-2024.

Butler, M.S., Blaskovich, M.A., & Cooper, M.A. (2013) Antibiotics in the clinical pipeline in 2013. Journal of Antibiotics Research, 66, 571-591

Chen, C., Ye, Y., Wang, R., Zhang, Y., Wu, C., Debnath, S.C., Ma, Z., Wang, J., & Wu, M. (2018) Streptomyces nigra sp. nov. is a novel actinobacterium isolated from mangrove soil and exerts a potent antitumor activity in vitro. Frontiers in Microbiology, 9, 1587.

Chen, H., Wan, C., & Zhang, L. (2019) A new diketopiperazine isolated from a Nocardiopsis strain TRM20105 guided by bioassay against Candida albicans. Natural Product Research,33,3421-3425.

Chen, M.H., Zhang, W.L., Chen, L., Lin, R., Xie, Y., Fang, D.S., Lian, Y.Y., & Jiang, H. (2019) Isolation, purification and identification of two new alkaloids metabolites from marine-derived Verrucosispora sp. FIM06025. Natural Product Research 33:2897-2903.

Chen, P., Zhang, L., Guo, X., Dai, X., Liu, L., Xi, L., Wang, J., Song, L., Wang, Y., Zhu, Y., Huang, L., & Huang, Y. (2016). Diversity, biogeography, and biodegradation potential of actinobacteria in the deep-sea sediments along the Southwest Indian ridge. Frontiers in Microbiology, 7, 1340.

Dalisay, D.S., Williams, D.E., Wang, X.L., Centko, R., Chen, J., & Andersen, J.E. (2013). Marine sediment-derived Streptomyces bacteria from British Columbia, Canada are a promising microbiota resource for the discovery of antimicrobial natural products. PLoS ONE, 8(10).

Joseph, J., Abirami, B., Manigundan, K., Gopikrishnan, V., & Radhakrishnan, M. (2021) Antimicrobial peptides from Actinobacteria: Current status and future prospects. In: Microbial and Natural Macromolecules, Academic Press, pp 205-231.

Kamaruddin, M.F., Hossain, M.Z., Alabsi, A.M., & Bakri, M.M. (2019). The antiproliferative and apoptotic effects of capsaicin on an oral squamous cancer cell line of asian origin, ORL-48. Medicina, 55, 322.

Karthikeyan, A., Joseph, A. & Nair, B.G. (2022) Promising bioactive compounds from the marine environment and their potential effects on various diseases. Journal of Genetic Engineering and Biotechnology, 20, 14.

Kemung, H.M., Tan, L.T.H., Khan, T.M., Chan, K.G., Pusparajah, P., Goh, B.H., & Lee, L.H. (2018) Streptomycesas a Prominent Resource of future anti-MRSA drugs. Frontiers in Microbiology, 9, 2221.

Kim, H., Kim, S., Kim, M., Lee, C., Yang, I., & Nam, S.J. (2020). Bioactive natural products from the genus Salinospora: a review. Archives of Pharmacal Research, 43(12), 1230-1258.

Kim, M.C., Machado, H., Jang, K.H., Trzoss, L., Jensen, P.R., & Fenical, W. (2018). Integration of genomic data with NMR analysis enables assignment of the full stereostructure of Neaumycin B, a potent inhibitor of glioblastoma from a marine-derived micromonospora. Journal of the American Chemical Society, 140, 10775-10784

Lee, H.S., & Jeong, G.S. (2020) Salinosporamide A, a Marine-Derived Proteasome Inhibitor, Inhibits T Cell Activation through Regulating Proliferation and the Cell Cycle. Molecules, 25, 5031.

Letzel, A.C., Li, J., Amos, G., Milla- Aguinaga, N., Ginigini, J., Abdelmohsen, U.R., Gaudencio, S., Ziemert, N., Moore, B.S., & Jensen, P.R. (2017) Genomic Insights into Specialized Metabolism in the Marine Actinomycete Salinispora. Environmental Microbiology, 19, 3660-3673.

Lu, S., Wang, J., Sheng, R., Fang, Y., & Guo, R. (2020) Novel Bioactive Polyketides Isolated from Marine Actinomycetes: An Update Review from 2013 to 2019. Chemical Biodiversity, 17(12).

Matuo, R., Sousa, F.G., Soares, D.G., Bonatto, D., Saffi, J., Escargueil, A.E., ... & Henriques, J.A.P. (2012). Saccharomyces cerevisiae as a model system to study the response to anticancer agents. Cancer Chemotherapy and Pharmacology, 70(4), 491-502.

McKinnie, S.M., Miles, Z.D., Jordan, P.A., Awakawa, T., Pepper, H.P., Murray, L.A., George, J.H., & Moore, B.S. (2018) Total enzyme syntheses of napyradiomycins A1 and B1. Journal of the American Chemical Society, 140, 7840-17845.

Menacho-Márquez, M., Murguía, J.R. (2007). Yeast on drugs: Saccharomyces cerevisiae as a tool for anticancer drug research. Clinical Translational Oncology, 9(4), 221-228

Mohr, K.I. (2016). History of antibiotics research. Current Topics in Microbiology and Immunology, 398, 237-272.

Myers, J.A., Curtis, B.S., & Curtis, W.R. (2013) Improving accuracy of cell and chromophore concentration measurements using optical density. BMC Biophysics, 6, 4.

Patterson, J.O., Swaffer, M., & Filby, A. (2015). An imaging flow cytometry-based approach to analyse the fission yeast cell cycle in fixed cells. Methods, 82, 74-84.

Perez, L.B., & Fenical, W. (2017). Accessing marine microbial diversity for drug discovery. In: Microbial Resources, Academic Press, pp 169-187.

Robertson, J., McGoverin, C., Vanholsbeeck, F., & Swift, S. (2019). Optimization of the protocol for the LIVE/DEAD® BacLightTM bacterial viability kit for rapid determination of bacterial load. Frontiers in Microbiology,10, 801

Rudolf, J.D., Yan, X., & Shen, B. (2016) Genome neighborhood network reveals insights into enediyne biosynthesis and facilitates prediction and prioritization for discovery. Journal of Industrial Microbiology and Biotechnology, 43(2-3), 261-276.

Sabido, E.M., Tenebro, C.P., Suarez, A.F.L., Ong, S.D.C., Trono, D.J.V.L., Amago, D.S., Evangelista, J.E. Jr., Reynoso, A.M.Q., Villalobos, I.G.M., Alit, L.D.D., Surigao, C.F., Villanueva, C.A., Saludes, J.P., & Dalisay, D.S. (2020). Marine sediment-derived streptomyces strain produces angucycline antibiotics against multidrug-resistant Staphylococcus aureus harboring SCCmec type 1 gene. Journal of Marine Science and Engineering, 8, 734.

Sabido, E. M., Tenebro, C. P., Trono, D. J. V. L., Vicera, C. V. B., Leonida, S. F. L., Maybay, J. J. W. B., Reyes-Salarda, R., Amago, D. S., Aguadera, A. M. V., Octaviano, M. C., Saludes, J. P., & Dalisay, D. S. (2021). Insights into the variation in bioactivities of closely related Streptomyces strains from marine sediments of the Visayan sea against ESKAPE and ovarian cancer. Marine Drugs, 19, 441.

Sanchez-Pico, A., Leon-Gonzalez, A.J., Martin-Cordero, C., & Daga, R.R. (2014). Screening for natural anticancer agents using fission yeast bioassay. Phytochemistry Letters, 8, 184-189.

Serrano-Aparicio, N., Moliner, V., & Swiderek, K. (2021). On the origin of the different reversible characters of salinosporamide A and homosalinosporamide A in the covalent inhibition of the human 20s proteasome. ACS Catalysis, 11(18), 11806-11819.

Sharma, A., & Nandi, S. (2020). Abnormal signal transduction via over-expression of Pim-1 regulated senescence, cell cycle, apoptosis and metastatic invasion: novel anticancer targets and their potent inhibitors from marine sources. Current Signal Transduction Therapy, 15(1), 3-11.

Sletta, H., Degnes, K.F., Herfindal, L., Klinkenberg, G., Fjærvik, E., Zahlsen, K., ... & Zotchev, S. B. (2014). Anti-microbial and cytotoxic 1, 6-dihydroxyphenazine-5, 10-dioxide (iodinin) produced by Streptosporangium sp. DSM 45942 isolated from the fjord sediment. Applied Microbiology and Biotechnology, 98(2), 603-610.

Sung, H., Ferlay, J., Siegel, R.L., Laversanne, M., Soergomataram, I., Jemal, A., & Bray, F. (2021) Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 71, 209-249.

Trotsko, N., Przekora, A., Zalewska, J., Ginalska, G., Paneth, A., & Wujec, M. (2018) Synthesis and in vitro antiproliferative and antibacterial activity of new thiazolidine-2, 4-dione derivatives. Journal of Enzyme Inhibition and Medicinal Chemistry, 33, 17-24.

Xu, L., Ye, K-X., Dai, W-H., Sun, C., Xu, L-H., & Han, B-N. (2019). Comparative genomic insights into secondary metabolism biosynthetic gene cluster distributions of marine Streptomyces. Marine Drugs, 17, 498.

Yao, J., Deng, K., Huang, J., Zeng, R., & Zuo, J. (2020). Progress in the understanding of the mechanism of tamoxifen resistance in breast cancer. Frontiers in Pharmacology, 11, 592912.

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