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It is well documented that curcumin (CUR), as a polyphenol molecule originated from turmeric, has many advantages such as antioxidative, anti-inflammatory, neuroprotective, and antitumor effects. However, because of its poor water solubility and low bioavailability, the biomedical applications of CUR are limited. So, in this study, we modified CUR with conjugation to a food-derived hydrophilic hydroxyethyl starch (HES) via an ester linkage to fabricate the amphiphilic conjugate HES-CUR prior to self-assembling into uniform nanoparticles (HES-CUR NPs). And, the results of the 1H NMR spectra and FT-IR spectrum showed successful synthesis of HES-CUR NPs; moreover, the solubility and the drug loading efficiency of CUR were significantly increased. Next, we further explored the differences on the antitumor effects between HES-CUR NPs and CUR in HepG2 cells, and the results of the CCK8-assay and cell counting experiment showed that HES-CUR NPs exhibited a more significant antiproliferative effect than that of CUR in HepG2 cells. And HepG2 cells were more sensitive to apoptosis induced by HES-CUR NPs as evidenced by flow cytometry, increased cytochrome c level, and decreased full length caspase-3 and Bcl-2 protein expressions. Additionally, we found that the efficacy of HES-CUR NPs against HepG2 cells might be related to the enhanced degree of mitochondrial damage (decrease of the mitochondrial membrane potential and ATP) and autophagy (increased levels of Beclin-1 and LC3-II proteins). So, the findings in this study suggest that HES-CUR NPs have a great application potential in antitumor efficacy and play an important role in multiple signal pathways.

Chlamydia trachomatis is an important human pathogen responsible for a variety of important diseases. pORF5, a plasmid protein in C. trachomatis, has been reported to contribute to chlamydial pathogenesis. Apoptosis and autophagy are two important cellular processes, which also participate in the pathological and the physiological processes in C. trachomatis infection. The present study aimed to explore the effects of pORF5 protein on autophagy and apoptosis in HeLa cells. Stable pORF5-HeLa and vector-HeLa cell lines that were transduced with pORF5 recombination lentivirus and control lentivirus, respectively, were constructed. Immunofluorescence was used to observe the cells. Western blotting was carried out to detect expression of target proteins. Real-time polymerase chain reaction was used to determine the mRNA expression. Flow cytometry, TUNEL assay and Hoechst staining were employed to detect apoptosis. pORF5 sensitized HeLa cells to autophagy that was induced by nutrient deprivation. In addition, pORF5 increased the ratio of LC3-II/LC3-I and Beclin-1 expression, down-regulated the expression of Bax and Caspase-3 and up-regulated Bcl-2 expression to suppress apoptosis induced by TNF-α. Autophagy inhibitor 3-MA elevated apoptotic rate significantly in pORF5-HeLa cells. The study preliminarily confirms that plasmid protein pORF5 mediates the crosstalk between autophagy and apoptosis, which may contribute to persistent C. trachomatis infection in host cells.

Phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway performs a central role in tumorigenesis and is constitutively activated in many malignancies. As a novel dual PI3K/mTOR inhibitor currently undergoing evaluation in a phase I/II clinical trial, NVP-BEZ235 indicates a significant antitumor efficacy in diverse solid tumors, including colorectal cancer (CRC). Autophagy is a catabolic process that maintains cellular homeostasis and reduces diverse stresses through lysosomal recycling of the unnecessary and damaged cell components. This process is also observed to antagonize the antitumor efficacy of PI3K/mTOR inhibitor agents such as NVP-BEZ235, via apoptosis inhibition. In the present study, we investigated anti-proliferative and apoptosis-inducing ability of NVP-BEZ235 in SW480 cells and the crosstalk between autophagy and apoptosis in SW480 cells treated with NVP-BEZ235 in combination with an autophagy inhibitor. The results revealed that, NVP-BEZ235 effectively inhibit the growth of SW480 cells by targeting the PI3K/mTOR signaling pathway and induced apoptosis. The inhibition of autophagy with 3-methyladenine or chloroquine inhibitors in combination with NVP-BEZ235 in SW480 cells enhanced the apoptotic rate as componets to NVP-BEZ235 alone. In conclusion, the findings provide a rationale for chemotherapy targeting the PI3K/mTOR signaling pathway presenting a potential therapeutic strategy to enhance the efficacy of dual PI3K/mTOR inhibitor NVP-BEZ235 in combination with an autophagy inhibitor in CRC treatment and treatment of other tumors. [ABSTRACT FROM AUTHOR]