Saquayamycin B1 Suppresses Proliferation,Invasion, and Migration by Inhibiting PI3K/AKT Signaling Pathway in Human Colorectal Cancer Cells

Moromycin B (Mor B), saquayamycin B₁ (Saq B₁), saquayamycin B (Saq B), and landomycin N (Lan N), four angucyclines produced by the marine-derived actinomycete Streptomyces sp., are a class of polyketone compounds containing benzanthracene. Here, the structure–activity relationship of these four compounds was analyzed in human colorectal cancer (CRC) cells. Saq B₁, which showed the strongest cytotoxicity with an IC₅₀ of 0.18–0.84 µM for CRC cells in MTT assays, was employed to test underlying mechanisms of action in SW480 and SW620 cells (two invasive CRC cell lines). Our results showed that Saq B₁ inhibited CRC cell proliferation in a dose- and time-dependent manner. Notably, lower cytotoxicity was measured in normal human hepatocyte cells (QSG-7701). Furthermore, we observed proapoptosis, antimigration, and anti-invasion activities of Saq B₁ in CRC cells. At the same time, the protein and mRNA expression of important markers related to the epithelial–mesenchymal transition (EMT) and apoptosis changed, including N-cadherin, E-cadherin, and Bcl-2, in Saq B₁-treated CRC cells. Surprisingly, the PI3K/AKT signaling pathway was shown to be involved in Saq B₁-induced apoptosis, and in inhibiting invasion and migration. Computer docking models also suggested that Saq B₁ might bind to PI3Kα. Collectively, these results indicate that Saq B₁ effectively inhibited growth and decreased the motor ability of CRC cells by regulating the PI3K/AKT signaling pathway, which provides more possibilities for the development of drugs in the treatment of CRC.     

Dalapon resistance at an early seedling stage in Lolium perenne

The inhibitory effect of the herbicide dalapon on germination and shoot elongation was evaluated in two perennial ryegrass cultivars, Melino RvP and Cropper. These cultivars had been shown to be dalapon resistant and susceptible, respectively, in a previous comparison of 14-week-old plants. Dalapon (10^-2 and 10^-3 m) significantly reduced rates of germination and shoot elongation to the same extent in both cultivars. It is suggested that the effects of dalapon on germination and shoot elongation during the first 9 days of development are not indicative of levels of resistance in more mature plants.     

The influence of the herbicide methabenzthiazuron on the synthesis of plastidic lipids in Hordeum vulgare seedlings

The herbicide methabenzthiazuron, and inhibitor of the Hill reaction, was applied to Hordeum seeds at the time of sowing, and the greening process under continuous Fluora light was investigated to the age of 13 days. Chlorophyll and xanthophyll contents were increased by methabenzthiazuron relative to the controls, with degrading ratios of chlorophyll a/chlorophyll b and rising xanthophyll/carotene values. The enhanced ratios of chlorophyll a to lipoquinones, like the absolute values, indicate an inhibition of the lipoquinones. These metabolic alterations are similar to those found in shade-adapted leaves. It is suggested, therefore, that inhibition of the photosynthetic electron transport, like deficiency in light of shade leaves, is compensated by metabolic reactions leading to a greater amount of photosystem II with an enhanced accumulation of the light-trapping chlorophylls and carotenoids.     

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