Streptomyces sp. MUM256: A Source for Apoptosis Inducing and Cell Cycle-Arresting Bioactive Compounds against Colon Cancer Cells

Abstract

New and effective anticancer compounds are much needed as the incidence of cancer continues to rise. Microorganisms from a variety of environments are promising sources of new drugs; Streptomyces sp. MUM256, which was isolated from mangrove soil in Malaysia as part of our ongoing efforts to study mangrove resources, was shown to produce bioactive metabolites with chemopreventive potential. This present study is a continuation of our previous efforts and aimed to investigate the underlying mechanisms of the ethyl acetate fraction of MUM256 crude extract (MUM256 EA) in inhibiting the proliferation of HCT116 cells. Our data showed that MUM256 EA reduced proliferation of HCT116 cells via induction of cell-cycle arrest. Molecular studies revealed that MUM256 EA regulated the expression level of several important cell-cycle regulatory proteins. The results also demonstrated that MUM256 EA induced apoptosis in HCT116 cells mediated through the intrinsic pathway. Gas chromatography-mass spectrometry (GC-MS) analysis detected several chemical compounds present in MUM256 EA, including cyclic dipeptides which previous literature has reported to demonstrate various pharmacological properties. The cyclic dipeptides were further shown to inhibit HCT116 cells while exerting little to no toxicity on normal colon cells in this study. Taken together, the findings of this project highlight the important role of exploring the mangrove microorganisms as a bioresource which hold tremendous promise for the development of chemopreventive drugs against colorectal cancer.

Streptomyces sp. Strain MUSC 125 from Mangrove Soil in Malaysia with Anti-MRSA, Anti-Biofilm and Antioxidant Activities

“…In recent years, the search for Streptomyces is concentrated on the rather less explored ecological niches such as the mangrove forest to increase chances of finding new Streptomyces species with bioactive potentials [24,56,57]. An earlier study by Ser, et al [37] demonstrated the large genome size of Streptomyces sp.…”

Antioxidant Activities of Streptomyces sp. strain MUSC 14 from Mangrove Forest Soil in Malaysia

“…Because Malaysia is ideally located within the South-East Asian region, it offers an opportunity to explore its microbial community as it remains yet to be fully explored. Recent review by Ser et al [23] detailed the potential of Streptomyces from mangrove soil in Malaysia to produce biologically active metabolites with anticancer and antioxidant activities with addition to studies carried out by Kemung et al [10], Tan et al [28][29][30] and Law et al [31]. Meanwhile study by Ser et al [32] demonstrated Streptomyces as potential producers of antibacterial metabolites.…”

Streptomyces sp. strain MUSC 5 from mangrove forest in Malaysia: Identification, antioxidant potential and chemical profiling of its methanolic extract

“…The soil consists of a diverse microbial community which includes bacteria such as Streptomyces [13] and competition for nutrients can be extremely intense [14] . Nevertheless, Streptomyces adapted well to the surrounding environment and this may be justified by the fact that they carry a large genome size with high G-C content [15][16][17][18][19][20][21] that enable the production of vast array of enzymes, proteins and secondary metabolites to process variety of materials needed for growth and survival [22][23][24][25][26] . The genus of Streptomyces under the Actinobacteria phylum are by far the most recognized producers of current drugs and secondary metabolites with diverse biological activities [4,[27][28][29][30][31] .…”