Curdepsidone A Induces Intrinsic Apoptosis and Inhibits Protective Autophagy via the ROS/PI3K/AKT Signaling Pathway in HeLa Cells.

Among female oncology patients, cervical cancer stands as the fourth most prevalent malignancy, exerting significant impacts on their health. Over 600,000 women received the diagnosis of cervical cancer in 2020, and the illness claimed over 300,000 lives globally. Curdepsidone A, a derivative of depsidone, was isolated from the secondary metabolites of Curvularia sp. IFB-Z10. In this study, we revised the molecular structure of curdepsidone A and investigated the fundamental mechanism of the anti-tumor activity of curdepsidone A in HeLa cells for the first time. The results demonstrated that curdepsidone A caused G0/G1 phase arrest, triggered apoptosis via a mitochondrial apoptotic pathway, blocked the autophagic flux, suppressed the PI3K/AKT pathway, and increased the accumulation of reactive oxygen species (ROS) in HeLa cells. Furthermore, the PI3K inhibitor (LY294002) promoted apoptosis induced by curdepsidone A, while the PI3K agonist (IGF-1) eliminated such an effect. ROS scavenger (NAC) reduced curdepsidone A-induced cell apoptosis and the suppression of autophagy and the PI3K/AKT pathway. In conclusion, our results revealed that curdepsidone A hindered cell growth by causing cell cycle arrest, and promoted cell apoptosis by inhibiting autophagy and the ROS-mediated PI3K/AKT pathway. This study provides a molecular basis for the development of curdepsidone A as a new chemotherapy drug for cervical cancer.

DMC triggers MDA-MB-231 cells apoptosis via inhibiting protective autophagy and PI3K/AKT/mTOR pathway by enhancing ROS level.

DMC, a kind of compound derived from the dry flower buds of Cleistocalyx operculatus, has been shown to inhibit the growth of various cancer cells, but research on triple-negative breast cancer cells remains scarce. To explore this issue, MDA-MB-231 cells were selected, and the results showed that DMC has strong proliferation inhibit effects on this kind of cells. The inhibit rate of 30 µM DMC incubated for 24 h was 56.25%, and 40.6% cells were arrested under the G2/M phase. The levels of pro-apoptosis protein Bax and active caspase-3, cleaved PARP and cell cycle related proteins, such as p21 and p27 increased, but apoptosis regulators, like Bcl-2, Cdc 2, Cyclin B1, and LC3 II decreased dramatically. In addition, DMC induced the accumulation of autophagosomes and autophagic substrates, and the combination of DMC with CQ promoted apoptosis of MDA-MB-231 cells, which suggested that DMC induced apoptosis partly by blocking autophagy flow. Moreover, the phosphorylation levels of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), and its mechanistic target of rapamycin kinase (mTOR) were also decreased after 30 µM DMC incubating for 24 h. The proteins play a critical role in cell proliferation, apoptosis, and autophagy modulation. The inhibition of autophagy flow and PI3K/AKT/mTOR pathway could be reversed after being treated with ROS scavenger NAC. Altogether, the results of the present study suggest that DMC effectively induces apoptosis and growth inhibition in MDA-MB-231 cells through blocking autophagy flow and regulating the PI3K/AKT/mTOR pathway by increasing ROS level.

Whether membranes developed for organic solvent nanofiltration (OSN) tend to be hydrophilic or hydrophobic? ── a review.

In the past few decades, organic solvent nanofiltration (OSN) has attracted numerous researchers and broadly applied in various fields. Unlike conventional nanofiltration, OSN always faced a broad spectrum of solvents including polar solvents and non-polar solvents. Among those recently developed OSN membranes in lab-scale or widely used commercial membranes, researchers preferred to explore intrinsic materials or introduce nanomaterials into membranes to fabricate OSN membranes. However, the hydrophilicity of the membrane surface towards filtration performance was often ignored, which was the key factor in conventional aqueous nanofiltration. The influence of surface hydrophilicity on OSN performance was not studied systematically and thoroughly. Generally speaking, the hydrophilic OSN membranes performed well in the polar solvents while the hydrophobic OSN membranes work well in the non-polar solvent. Many review papers reviewed the basics, problems of the membranes, up-to-date studies, and applications at various levels. In this review, we have focused on the relationship between the surface hydrophilicity of OSN membranes and OSN performances. The history, theory, and mechanism of the OSN process were first recapped, followed by summarizing representative OSN research classified by surface hydrophilicity and types of membrane, which recent OSN research with its contact angles and filtration performance were listed. Finally, from the industrialization perspective, the application progress of hydrophilic and hydrophobic OSN membranes was introduced. We started with history and theory, presented many research and application cases of hydrophilic and hydrophobic OSN membranes, and discussed anticipated progress in the OSN field. Also, we pointed out some future research directions on the hydrophilicity of OSN membranes to deeply develop the effect made by membrane hydrophilicity on OSN performance for future considerations and stepping forward of the OSN industry.