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Anti-Cancer Agents in Medicinal Chemistry

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ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

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Research Article

Apoptosis-inducing Metabolite from Marine Mangrove Actinobacteria VITGAP173

Author(s): Ajitha Gomathi, Manikandan Alagumuthu, Pavan K.J.G. Sai, Harishkumar Madhyastha, Rama Jayaraj and Gothandam K. Muthukailannan*

Volume 24, Issue 13, 2024

Published on: 29 April, 2024

Page: [1009 - 1015] Pages: 7

DOI: 10.2174/1871520622666220523155905

Price: $65

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Abstract

Background: Marine actinobacteria have proven to be a remarkable source of bioactive metabolites.

Methods: The present study focused on the isolation of anticancer metabolites from marine actinobacteria. Streptomyces sp. VITGAP173 was found to have promising anticancer activity against breast cancer cell lines (MCF-7).

Results: Bioassay-guided fractionation was followed to identify the bioactive metabolites from crude ethyl acetate extract of VITGAP173, which yielded four fractions. Fraction B exhibited the highest cytotoxic activity against MCF-7 cell lines among the four fractions. Further structural characterization of the fraction was done by FTIR and NMR spectroscopy. The fraction-2 induced cytotoxicity against MCF-7 cell lines and the half maximal inhibition (IC50) value was calculated as 4.7 μg/ml. To elucidate the possible mechanism of cell death, MCF-7 cells were treated with fraction-2 for 24 hours and the morphological changes were examined using acridine orange – ethidium bromide (AO/EB) staining. The fraction also increased the reactive oxygen species (ROS) generation (Flow cytometry, DCFHDA). The molecular mechanism of fraction-induced cell death was analysed by real-time PCR, which revealed that the fraction promotes apoptosis through the CHOP-ATF-4 pathway involved in ER stress signalling.

Conclusion: The present findings suggested the apoptosis-inducing potential of fraction-2 in breast cancer therapy.

Keywords: Mangrove, actinobacteria, bioactive fraction, cytotoxic, apoptosis, ER stress

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[1]
Hasson, S.S.; H Al-Shubi, A.S.; Al-Busaidi, J.Z.; Al-Balushi, M.S.; Hakkim, F.L.; Rashan, L.; Aleemallah, G.M.; Al-Jabri, A.A. Potential of aucklandia lappa decne ethanolic extract to trigger apoptosis of human T47D and hela cells. Asian Pac. J. Cancer Prev., 2018, 19(7), 1917-1925.
[PMID: 30051673]
[2]
Newman, D.J.; Cragg, G.M. Natural products as sources of new drugs from 1981 to 2014. J. Nat. Prod., 2016, 79(3), 629-661.
[http://dx.doi.org/10.1021/acs.jnatprod.5b01055] [PMID: 26852623]
[3]
Bérdy, J. Bioactive microbial metabolites. J. Antibiot. (Tokyo), 2005, 58(1), 1-26.
[http://dx.doi.org/10.1038/ja.2005.1] [PMID: 15813176]
[4]
Challis, G.L.; Hopwood, D.A. Synergy and contingency as driving forces for the evolution of multiple secondary metabolite production by Streptomyces species. Proc. Natl. Acad. Sci. USA, 2003, 100(Suppl. 2), 14555-14561.
[http://dx.doi.org/10.1073/pnas.1934677100] [PMID: 12970466]
[5]
Hengartner, M.O. The biochemistry of apoptosis. Nature, 2000, 407(6805), 770-776.
[http://dx.doi.org/10.1038/35037710] [PMID: 11048727]
[6]
Jeong, S.Y.; Seol, D.W. The role of mitochondria in apoptosis. BMB Rep., 2008, 41(1), 11-22.
[http://dx.doi.org/10.5483/BMBRep.2008.41.1.011] [PMID: 18304445]
[7]
McConkey, D.J. Therapy-induced apoptosis in primary tumors. Adv. Exp. Med. Biol., 2007, 608, 31-51.
[http://dx.doi.org/10.1007/978-0-387-74039-3_3] [PMID: 17993231]
[8]
Mow, B.M.; Blajeski, A.L.; Chandra, J.; Kaufmann, S.H. Apoptosis and the response to anticancer therapy. Curr. Opin. Oncol., 2001, 13(6), 453-462.
[http://dx.doi.org/10.1097/00001622-200111000-00007] [PMID: 11673685]
[9]
Chen, S.S.; Michael, A.; Butler-Manuel, S.A. Advances in the treatment of ovarian cancer: a potential role of antiinflammatory phytochemicals. Discov. Med., 2012, 13(68), 7-17.
[PMID: 22284780]
[10]
Sinha, S.; Roy, S.; Reddy, B.S.; Pal, K.; Sudhakar, G.; Iyer, S.; Dutta, S.; Wang, E.; Vohra, P.K.; Roy, K.R.; Reddanna, P.; Mukhopadhyay, D.; Banerjee, R. A lipid-modified estrogen derivative that treats breast cancer independent of estrogen receptor expression through simultaneous induction of autophagy and apoptosis. Mol. Cancer Res., 2011, 9(3), 364-374.
[http://dx.doi.org/10.1158/1541-7786.MCR-10-0526] [PMID: 21289296]
[11]
Ron, D.; Walter, P. Signal integration in the endoplasmic reticulum unfolded protein response. Nat. Rev. Mol. Cell Biol., 2007, 8(7), 519-529.
[http://dx.doi.org/10.1038/nrm2199] [PMID: 17565364]
[12]
Gomathi, A.; Gothandam, K.M. Investigation of anti-inflammatory and toxicity effects of mangrove-derived Streptomyces rochei strain VITGAP173. J. Cell. Biochem., 2019, 120(10), 17080-17097.
[http://dx.doi.org/10.1002/jcb.28969] [PMID: 31104317]
[13]
Lee, C.H.; Lim, H.; Moon, S.; Shin, C.; Kim, S.; Kim, B.J.; Lim, Y. Novel anticancer agent, benzyldihydroxyoctenone, isolated from Streptomyces sp. causes G1 cell cycle arrest and induces apoptosis of HeLa cells. Cancer Sci., 2007, 98(6), 795-802.
[http://dx.doi.org/10.1111/j.1349-7006.2007.00473.x] [PMID: 17433036]
[14]
Macherla, V.R.; Liu, J.; Bellows, C.; Teisan, S.; Nicholson, B.; Lam, K.S.; Potts, B.C.; Glaciapyrroles, A.; Glaciapyrroles, A. B, and C, pyrrolosesquiterpenes from a Streptomyces sp. isolated from an Alaskan marine sediment. J. Nat. Prod., 2005, 68(5), 780-783.
[http://dx.doi.org/10.1021/np049597c] [PMID: 15921430]
[15]
Wang, R.; Li, C.; Song, D.; Zhao, G.; Zhao, L.; Jing, Y. Ethacrynic acid butyl-ester induces apoptosis in leukemia cells through a hydrogen peroxide mediated pathway independent of glutathione S-transferase P1-1 inhibition. Cancer Res., 2007, 67(16), 7856-7864.
[http://dx.doi.org/10.1158/0008-5472.CAN-07-0151] [PMID: 17699792]
[16]
Szatrowski, T.P.; Nathan, C.F. Production of large amounts of hydrogen peroxide by human tumor cells. Cancer Res., 1991, 51(3), 794-798.
[PMID: 1846317]
[17]
Schumacker, P.T. Reactive oxygen species in cancer cells: live by the sword, die by the sword. Cancer Cell, 2006, 10(3), 175-176.
[http://dx.doi.org/10.1016/j.ccr.2006.08.015] [PMID: 16959608]
[18]
Trachootham, D.; Zhou, Y.; Zhang, H.; Demizu, Y.; Chen, Z.; Pelicano, H.; Chiao, P.J.; Achanta, G.; Arlinghaus, R.B.; Liu, J.; Huang, P. Selective killing of oncogenically transformed cells through a ROS-mediated mechanism by beta-phenylethyl isothiocyanate. Cancer Cell, 2006, 10(3), 241-252.
[http://dx.doi.org/10.1016/j.ccr.2006.08.009] [PMID: 16959615]
[19]
Yoon, D.H.; Lim, M.H.; Lee, Y.R.; Sung, G.H.; Lee, T.H.; Jeon, B.H.; Cho, J.Y.; Song, W.O.; Park, H.; Choi, S.; Kim, T.W. A novel synthetic analog of Militarin, MA-1 induces mitochondrial dependent apoptosis by ROS generation in human lung cancer cells. Toxicol. Appl. Pharmacol., 2013, 273(3), 659-671.
[http://dx.doi.org/10.1016/j.taap.2013.10.015] [PMID: 24161344]
[20]
Wang, D.; Wong, H.K.; Feng, Y.B.; Zhang, Z.J. 18beta-glycyrrhetinic acid induces apoptosis in pituitary adenoma cells via ROS/MAPKs-mediated pathway. J. Neurooncol., 2014, 116(2), 221-230.
[http://dx.doi.org/10.1007/s11060-013-1292-2] [PMID: 24162829]
[21]
Jiang, Y.; Wang, X.; Hu, D. Furanodienone induces G0/G1 arrest and causes apoptosis via the ROS/MAPKs-mediated caspase-dependent pathway in human colorectal cancer cells: a study in vitro and in vivo. Cell Death Dis., 2017, 8(5), e2815.
[http://dx.doi.org/10.1038/cddis.2017.220] [PMID: 28542135]
[22]
Zheng, T.S.; Hunot, S.; Kuida, K.; Momoi, T.; Srinivasan, A.; Nicholson, D.W.; Lazebnik, Y.; Flavell, R.A. Deficiency in caspase-9 or caspase-3 induces compensatory caspase activation. Nat. Med., 2000, 6(11), 1241-1247.
[http://dx.doi.org/10.1038/81343] [PMID: 11062535]
[23]
Adams, J.M.; Cory, S. The Bcl-2 protein family: arbiters of cell survival. Science, 1998, 281(5381), 1322-1326.
[http://dx.doi.org/10.1126/science.281.5381.1322] [PMID: 9735050]

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