Wahome Paul G, Beauchesne Kevin R, Pedone Anna C, Cavanagh John, Melander Christian, Zimba Paul, Moeller Peter D R
Biosortia Pharmaceuticals, 565 Metro Place South, Suite 300, Dublin, OH 43017, USA.
Department of Molecular & Structural Biochemistry, North Carolina State University, Campus Box 7622, 128 Polk Hall, Raleigh, NC 27695, USA.
Mar Drugs. 2014 Dec 26;13(1):65-75. doi: 10.3390/md13010065.
Aquatic microbes produce diverse secondary metabolites with interesting biological activities. Cytotoxic metabolites have the potential to become lead compounds or drugs for cancer treatment. Many cytotoxic compounds, however, show undesirable toxicity at higher concentrations. Such undesirable activity may be reduced or eliminated by using lower doses of the cytotoxic compound in combination with another compound that modulates its activity. Here, we have examined the cytotoxicity of four microbial metabolites [ethyl N-(2-phenethyl) carbamate (NP-1), Euglenophycin, Anabaenopeptin, and Glycolipid 652] using three in vitro cell lines [human breast cancer cells (MCF-7), mouse neuroblastoma cells (N2a), and rat pituitary epithelial cells (GH4C1)]. The compounds showed variable cytotoxicity, with Euglenophycin displaying specificity for N2a cells. We have also examined the modulatory power of NP-1 on the cytotoxicity of the other three compounds and found that at a permissible concentration (125 µg/mL), NP-1 sensitized N2a and MCF-7 cells to Euglenophycin and Glycolipid 652 induced cytotoxicity.
水生微生物产生具有有趣生物活性的多种次生代谢产物。细胞毒性代谢产物有潜力成为癌症治疗的先导化合物或药物。然而，许多细胞毒性化合物在较高浓度时表现出不良毒性。通过使用较低剂量的细胞毒性化合物与另一种调节其活性的化合物联合使用，这种不良活性可能会降低或消除。在此，我们使用三种体外细胞系[人乳腺癌细胞（MCF-7）、小鼠神经母细胞瘤细胞（N2a）和大鼠垂体上皮细胞（GH4C1）]检测了四种微生物代谢产物[N-(2-苯乙基)氨基甲酸乙酯（NP-1）、裸藻霉素、鱼腥藻毒素和糖脂652]的细胞毒性。这些化合物表现出不同的细胞毒性，裸藻霉素对N2a细胞具有特异性。我们还检测了NP-1对其他三种化合物细胞毒性的调节作用，发现处于允许浓度（125 µg/mL）时，NP-1使N2a和MCF-7细胞对裸藻霉素和糖脂652诱导的细胞毒性敏感。
