Design and Synthesis of 7-Azaindole Derivatives and Their Antitumor and Analgesic Activities

To develop effective anti-tumor and analgesic drugs, a series of novel 7-azaindole derivatives were designed and synthesized through a four-step reaction. 18 target compounds were obtained and characterized through Nuclear Magnetic Resonance and High Resolution Mass Spectrometry. Their anti-proliferative activities and analgesic effect were evaluated. When the 1-position was a methylsulfonyl group and the 5-position was a nitro group, compound 4f demonstrated the best activity. Furthermore, there was a dramatic difference between the IC50 values of compound 4f in tumor and in healthy cell line. The IC50 values of compound 4f in MCF7 breast cancer cell line was 5.781 μmol/L and 8.077 μmol/L in HepG2 hepatoma carcinoma cell line, but more than 100 μmol/L in HL7702 liver cell line. Preliminary results showed that compounds 3a, 3g and 4i had significant analgesic effects in mice, which were stronger than aspirin. These compounds have good prospects for new drug development.

Growth Inhibition of a Novel Iron Chelator, DpdtC, against Hepatoma Carcinoma Cell Lines Partly Attributed to Ferritinophagy-Mediated Lysosomal ROS Generation

Some iron chelators display significant anticancer activity that may involve ferritin degradation either in proteasomes or in lysosomes, and the latter might involve ferritinophagy with a period. However, the correlation of ferritinophagy with anticancer activity of iron chelator was not fully determined. Revealing the underlying link therefore is required. Di-2-pyridylketone dithiocarbamate (DpdtC), a novel iron chelator, could mobilize iron from ferritin and displayed excellent antitumor against hepatoma carcinoma cell lines (IC50s = 0.4 ± 0.2 for HepG2 and 3.5 ± 0.3 μM for Bel-7402, resp.); we speculated that the antiproliferative action of DpdtC might involve ferritinophagy. To this end, the alterations of ferritin, microtubule-associated protein light chain 3 (LC3-II), and nuclear receptor coactivator 4 (NCOA4) were investigated after exposure of DpdtC to the cells. The results revealed that DpdtC could cause increases of autophagic vacuoles and LC3-II. The data from cellular immunofluorescence and Western blotting showed a reciprocal relation between abundances of ferritin and LC3-II, but the trends of NCOA4 and LC3-II in abundance were in a similar manner, indicating that a ferritinophagy occurred. Further studies revealed that the ferritinophagy evoked an iron-driven intralysosomal oxidative reaction, resulting in LMP change and lipid peroxidation. Thus, a ferritinophagy-mediated lysosomal ROS generation playing a role in the antiproliferative action of DpdtC could be proposed, which will enrich our knowledge of iron chelator in cancer therapy.

Enrichment Efficiency Optimization of Dielectrophoresis Cell Chip Based on Interdigitated Microelectrodes Array

At present, the majority dielectrophoresis chip designs optimize their performance by electric simulation and fluid field simulation. The lack of further cells force analysis and movement prediction results in a limited cell dielectrophoresis enrichment efficiency. The HepG2 hepatoma carcinoma cell movement under the action of dielectrophoresis force, fluid force and gravity was analyzed respectively by Comsol Multiphysics software. The preliminary optimization conditions for the cell enrichment were obtained. According to the simulation results, the experiments were carried out to investigate the enrichment effect of the HepG2 hepatoma carcinoma cells. The experiment result demonstrated the enrichment efficiency of HepG2 hepatoma carcinoma cells was reached to 88.89% under the 5 V amplitude and 4 MHz frequency sinusoidal signal excitation.

In VitroandIn VivoAntitumor Effects of n-Butanol Extracts ofPterocephalus hookerion Hep3B Cancer Cell

Pterocephalus hookeriis a widely applied Tibetan medicinal prescription for treatment of diseases such as flu, rheumatoid arthritis, and enteritis in China. It has been reported thatPterocephalus hookerihas anti-inflammatory and analgesic actions. However, the antitumor activity ofPterocephalus hookeriremains unknown. In the present study, we demonstrate that n-butanol extracts ofPterocephalus hookeri(YSC-ZDC) has a strong antitumor activity against hepatoma carcinoma cellin vitroandin vivo. YSC-ZDC inhibited proliferation of all cancer cell lines and significantly inhibited Hep3B cells proliferation in a dose- and time-dependant manner. Transmission electron microscopy, hoechst 33258 staining, and flow cytometry analysis revealed that YSC-ZDC induced apoptosis in Hep3B cells. YSC-ZDC treatment dramatically inhibited PDK1 and Akt phosphorylation in Hep3B cells. Moreover, YSC-ZDC increased Bax expression and inhibited Bcl-2 expression. In addition, YSC-ZDC inhibited growth hepatoma xenograftsin vivowith no effect on body weight and spleen index. Consistent with resultsin vitro, YSC-ZDC increased Bax expression and inhibited Bcl-2 expression in tumor tissue. Taken together, this study shows YSC-ZDC with an antitumor activity bothin vitroandin vivo. Its mechanism underlying is related to blocking of the Akt pathway and regulation of Bcl-2 family proteins expression.