Abstract
The marine environment has a remarkable source of natural products mainly from marine fungi, which have been a central source of novel pharmacologically bioactive secondary metabolites. In this study, the search for a new potential apoptosis-inducing metabolite is focused on marine sponge-associated symbionts. A total of sixteen different sponges were obtained from the Gulf of Mannar region, India, and twenty-three different marine fungal strains were isolated and tested for antiproliferative activity by the MTT assay. Out of these, Monascus sp. NMK7 associated with the marine sponge Clathria frondifera was found to have a promising antiproliferative property. Furthermore, to isolate the pure active metabolite, the crude material was subjected to column chromatography and HPLC. Structural characterization was conducted by a variety of spectroscopic techniques including UV, IR, MS and NMR. The obtained results from the MS and NMR spectroscopy determined 418.5 Da to be the molecular weight and C24H34O6 to be the molecular formula of the metabolite, indicating the presence of monacolin X (NMKD7). NMKD7 was found to induce dose-dependent cytotoxicity in different human breast cancer cell lines MCF-7, T47D, MDA-MB-231, MDA-MB-468 and MCF-10A normal breast cell after 24 h of exposure. For elucidating the possible mode of cell death, T47D and MDA-MB-468 cells were treated with NMKD7 for 24 h to examine the morphological change of the chromatin (PI & AO/EB). Therefore, it has been suggested as the possible mechanism of apoptosis, and apart from this, it has also exhibited antibacterial and anti-migratory properties as well as induced the ROS stress (DCFH-DA), which causes the mitochondrial membrane potential difference (Rhodamine-123), the loss of cell membrane integrity and eventually cell death. Thus, the present study features a novel promising apoptosis-inducing metabolite (NMKD7) with minimal toxicity, suggesting its potential for biotechnological applications, and substantiates that it should be further considered for the elucidation of molecular targets and signal transduction pathways.
Highlights
The increasing incidences of cancer have led to a global burden to nd many diverse therapeutic treatments including surgery, radiation and chemotherapy.[1]
Identi cation of NMKD7-producing fungi associated with the marine sponge
The marine sponge (Sp4) was taxonomically identi ed based on its morphology and the spicule structure as Clathria frondifera by Dr Siva Leela, a scientist in Zoological Survey of India (ZSI), MBRC, Chennai, Tamil Nadu, India
Summary
The increasing incidences of cancer have led to a global burden to nd many diverse therapeutic treatments including surgery, radiation and chemotherapy.[1] A large portion of the drugs are targeted for the signaling pathways responsible for cell proliferation and survival.[2] Cancer fungotherapy is a promising scienti c eld that deals with antitumor metabolites derived from fungi,[3] the initiation of apoptosis and the limiting of sti ing cell proliferation in cancer cells with minimal or no side effects. Marine fungal metabolites are in the limelight of the drug discovery area as they are very effective therapeutic agents. The microorganisms for the 5878 | RSC Adv., 2019, 9, 5878–5890
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