Synthesis and screening of novel anthraquinone-quinazoline multitarget hybrids as promising anticancer candidates.

Aim: The EGF receptor (EGFR) is overexpressed in multiple epithelial-derived cancers and is considered to be a vital target closely associated with cancer therapy. In this study, a series of novel anthraquinone-quinazoline hybrids targeting several vital sites for cancer therapy were designed and synthesized. Methodology & results: Most of the synthesized hybrids demonstrated excellent antiproliferative activity and downregulation of the expression of EGFR. The most promising compound 7d showed the strongest antiproliferation activity; this compound significantly downregulated the expression of p-EGFR protein, induced a remarkable apoptosis effect, promoted the rearrangement of F-actin filaments and destruction of cytoskeleton, induced DNA damage and enhanced radiosensitivity of A549 cells. Conclusion: The novel anthraquinone-quinazoline hybrid 7d emerges as an anticancer drug candidate with promising multitargeted biological activities.

Effects of Rubiadin isolated from Prismatomeris connata on anti-hepatitis B virus activity in vitro.

Prismatomeris connata was a kind of Rubiaceae plant for treatment of hepatitis, hepatic fibrosis and silicosis. Whereas, the effective components of Prismatomeris connata remains unexplored. The aim of this study was to investigate the inhibitory effects and mechanisms of Rubiadin isolated from Prismatomeris connata against HBV using HepG2.2.15 cells. The levels of hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and hepatitis B core antigen (HBcAg) in the supernatants or cytoplasm were examined using by enzyme-linked immunosorbent assay. HBV DNA was qualified q-PCR. Rubiadin was isolated by silica gel column. The structure of the compound was elucidated by HPLC, FT-IR, 1 H-NMR, 13 C-NMR and identified as 1,3-Dihydroxy-2-methyl-9, 10-anthraquinone. Rubiadin significantly decreased HBeAg,HBcAg secretion level and inhibit HBV DNA replication. Rubiadin inhibits the proliferation of the cells and HBx protein expression in a dose-dependent manner. The intracellular calcium concentration was significantly reduced. These results demonstrated that Rubiadin could inhibit HepG2.2.15 cells proliferation, reduce the level of HBx expression, and intracellular free calcium, which might become a novel anti-HBV drug candidate.

Characterization of the mechanisms of electrochemotherapy in an in vitro model for human cervical cancer.

Electrochemical treatment is among the most effective therapies in the management of cervical malignancy. However, the mechanism of action of this treatment remains largely unknown. Therefore, the purpose of the current project was to establish a suitable eletrochemotherapy regimen for cervical cancer and to investigate the mechanism of the therapy in an in vitro model for human cervical carcinoma. HeLa cells were used as a model for cervical cancer in this study, and the effect of electrochemical treatment on these cells was examined in four different dosage groups (5 V + 5 C, 10 V + 5 C, 5 V + 10 C and 10 V + 10 C). Our results showed that the combinations of lower voltage and higher current (5 V/10 V + 10 C) had a greater anticancer effect in this model as compared to other groups. In addition, we compared the cytotoxic effect between electrochemical treatment and different pH condition treatments in this system, and found that the efficacy of electrochemical treatment in cell killing was better than that of acidic or basic medium treatment. Moreover, we demonstrated that the efficacy of electrochemical treatment was correlated with the degree of ionization and alteration in pH scale. The electrodes were basic on the cathode side which elevated the cations K+, Ca2+ and Mg2+, while the electrodes were acidic on the anode side which reduced the anion Cl-. We also assessed the effect of electrochemical treatment on cell cycle distribution in HeLa cells and showed that the percentage of cells in the G1 phase of the cell cycle was increased (G1 arrest), while the cell population in the S phase was decreased. Furthermore, we demonstrated that the levels of the cell cycle regulator cyclin D1 expression were dramatically reduced when 5 V/10 V + 10 C treatments were applied to these cells, as determined by RT-PCR analysis. By contrast, no significant changes in the levels of cyclin B1, CDK1 or CDK4 were detected. Based on these observations, we conclude that the combination of lower voltage and higher current may be a potentially effective eletrochemotherapy regimen for cervical cancer in the clinic, and that the antitumor effect of electrochemical treatment on cervical carcinoma cells is mediated partly via regulating ionization degree, pH state and cell cycle control.

[Effects of wogonin on inducing apoptosis of human ovarian cancer A2780 cells and telomerase activity].

BACKGROUND & OBJECTIVE: Inducing apoptosis and inhibiting the telomerase activity of tumor cells became a new therapeutic means for tumor. In vivo and in vitro experiments showed that wogonin possesses antioxidant activities and inhibitory effect on tumor cells growth. This study was designed to evaluate the effect of wogonin on telomerase activity and apoptosis of human ovarian carcinoma cell line A2780. METHODS: MTT assay,fluorescent microscopy,and DNA agarose gel electrophoresis were used to determine the role of wogonin on apoptosis of A2780 cells. The telomerase activity of A2780 cells were observed by using TRAP-ELASA method. RESULTS: A2780 cell growth was significantly inhibited by wogonin. The inhibiting effect showed concentration-dependent and time-dependent manners with IC(50) of 85 microg/ml. After treatment with 50 microg/ml and 100 microg/ml wogonin for 48 hours, A2780 cells showed morphological changes associated with the characters of apoptosis under fluorescent microscope. Typical DNA ladder was found using agarose gel electrophoresis. Telomerase activity of A2780 cells was gradually decreased with the increasing of wogonin concentration. When the concentration of wogonin was higher than 200 microg/ml, telomerase activity of A2780 cells was inhibited markedly. CONCLUSION: Wogonin can inhibit proliferation and induce apoptosis of A2780 cells within a certain concentration range(50-250 microg/ml). Anticancer effects of wogonin were associated with the induction of apoptosis and partly with the suppression of telomerase activity.