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Marine sponge-derived smenospongine preferentially eliminates breast cancer stem-like cells via p38/AMPK? pathways.

ABSTRACT: Breast cancer stem cells (CSCs) have been postulated as responsible for therapeutic failure of breast cancer. Novel agents effectively targeting breast CSCs are urging to be discovered to overcome cancer relapse and metastasis. We recently established a CSC-like model through ectopic expression Nanog, a core pluripotency factor, in breast cancer cells and validated induced CSC-like (MCF7-Nanog) model acquired stem-like properties. Using this model, we found that smenospongine (Sme), a natural sesquiterpene aminoquinone isolated from marine sponge Spongia pertusa Esper, preferentially inhibited the induced CSC-like cells proliferation by inducing G0/G1 arrest and intrinsic apoptosis via increasing the phosphorylation level of p38 and AMPK?. Importantly, Sme exhibited the ability to abrogate CSC-like cells associated with a downregulation of stem cell markers including Nanog, Sox2, and Bmi1. Functionally, Sme inhibited the ability of MCF7-Nanog cells to form tumor sphere in vitro and develop tumor in vivo. Significant antitumor effects are observed in Sme-treated mouse xenograft tumor models, with no apparent toxicity to mice. Taken together, our findings provide a CSC-like model to identify novel CSC-targeting drugs and identify Sme as a candidate natural agent for treatment of breast cancer.

SUBMITTER: Tang J

PROVIDER: S-EPMC6089165 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Marine sponge-derived smenospongine preferentially eliminates breast cancer stem-like cells via p38/AMPKα pathways.

Tang Jie J Wu Wei W Yang Fan F Liu Liyun L Yang Zhen Z Liu Li L Tang Weizhuo W Sun Fan F Lin Houwen H

Cancer medicine 20180707 8

Breast cancer stem cells (CSCs) have been postulated as responsible for therapeutic failure of breast cancer. Novel agents effectively targeting breast CSCs are urging to be discovered to overcome cancer relapse and metastasis. We recently established a CSC-like model through ectopic expression Nanog, a core pluripotency factor, in breast cancer cells and validated induced CSC-like (MCF7-Nanog) model acquired stem-like properties. Using this model, we found that smenospongine (Sme), a natural se ...[more]

PMID: 29982992

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Project description:Staphylococcus epidermidis, the common inhabitant of human skin and mucosal surfaces has emerged as an important pathogen in patients receiving surgical implants and medical devices. Entering the body via surgical sites and colonizing the medical devices through formation of multi-layered biofilms it leads to refractory and persistent device-related infections (DRIs). Staphylococcal proportions within biofilms are more tolerant to antibiotics and immune responses, and thus are hard-to-treat. The consequent morbidity and mortality, and economic losses in health care systems has strongly necessitated the need for development of new anti-bacterial and anti-biofilm based therapeutics. In this study, we describe the biological activity of a marine sponge-derived Streptomyces sp. SBT348 extract in restraining staphylococcal growth and biofilm formation on polystyrene, glass, medically relevant titan metal and silicone surfaces. A bio-assay guided fractionation was performed to isolate the active compound (C3) from the crude SBT348 extract. Our results demonstrated that C3 effectively inhibits the growth (MIC: 31.25 µg/ml) and biofilm formation (sub-MIC range: 1.95-<31.25 µg/ml) of S. epidermidis RP62A in vitro. Chemical characterization of C3 by heat and enzyme treatments, and High-Resolution Fourier Transform Mass Spectrometry (HRMS) revealed its heat-stable and non-proteinaceous nature, and high molecular weight (1258. 3257 Da). Cytotoxicity profiling of C3 in vitro on mouse fibroblast (NIH/3T3) and macrophage (J774.1) cell lines, and in vivo on the greater wax moth larvae Galleria melonella revealed its non-toxic nature at the effective dose. Transcriptome analysis of C3 treated-S. epidermidis RP62A has further unmasked the negative effect of C3 on central metabolism (carbon, amino acid and protein, lipids, nucleotide and energy) suggesting its mode of action. Taken together, these findings suggest that C3 could be possibly used as antibacterial and antibiofilm coatings on medically-relevant surfaces and prevent the relapsing staphylococcal DRIs.

Dataset Information

Marine sponge-derived smenospongine preferentially eliminates breast cancer stem-like cells via p38/AMPK? pathways.

Publications

Marine sponge-derived smenospongine preferentially eliminates breast cancer stem-like cells via p38/AMPKα pathways.

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