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Compared with vehicle treated BGC823 cells, proliferation was suppressed by treatment with high concentration of AZD6244 (3 and 4 M) for 24 hours and all given concentration of AZD6244 for 48 hours (D). Compared with vehicle treated SGC7901 cells, inhibition of proliferation was observed in cells treatment with high concentration of AZD6244 (2, 3 and 4 M) for 24 hours and all given concentration of AZD6244 (1, 2, 3 and 4 M) for 48 hours (C). [Extracted from the article]

Hepatocellular carcinoma (HCC) is the third leading cause of cancer‑associated mortality in the 21st century. microRNA (miR)‑23b has been shown to be involved in the pathogenesis of many cancers, including breast and prostate cancer. However, the role of miR‑23b in HCC remains unclear. The present study revealed a negative correlation between miR‑23b expression in HCC tissues and progression of carcinomas. Compared to normal tissues, miR‑23b expression was significantly downregulated in HCC tissues, whereas the expression of interleukin (IL)‑11 and IL‑11 receptor α (IL‑11Rα) was significantly upregulated, indicating that miR‑23b expression is negatively correlated with IL‑11 and IL‑11Rα expression. In addition, miR‑23b inhibited proliferation and promoted apoptosis of SMMC‑7721 cells. This effect was mediated by IL‑11, which was found to be the direct target of miR‑23b in this study. These results indicated that miR‑23b regulates IL‑11 and IL‑11Rα expression, and might act as an anti‑oncogenic agent in the progression of HCC by directly downregulating IL‑11 expression. [ABSTRACT FROM AUTHOR]

A novel series of pyrimidine-benzotriazole derivatives have been synthesized and evaluated for their anticancer activity against human solid tumor cell lines. The most promising molecule 12O was identified for its excellent antiproliferative activities, especially against the SiHa cell line with IC50 value as 0.009 μM. Kinase inhibition assay assessed 12O was a potential multi-kinase inhibitor, which possessed potent inhibitory activities against cyclin-dependent kinases (CDKs) and fms-like tyrosine kinase (FLT) with IC50 values in the nanomolar range. Molecular docking studies illustrated that the introduction of triazole moiety in 12O was critical for CDKs inhibition. In addition, 12O inhibited cancer cell proliferation, colony-formation, and cell cycle progression and provoked apoptotic death in vitro. In an SiHa xenograft mouse model, a once-daily dose of compound 12O at 20 mg/kg significantly suppressed the tumor growth without obvious toxicity. Taken together, 12O provided valuable guide for further structural optimization for CDKs and FLT inhibitors. [ABSTRACT FROM AUTHOR]

Background Accelerated proliferation of solid tumor and hematologic cancer cells is related to accelerated transcription of ribosomal DNA by the RNA polymerase I to produce elevated level of ribosomal RNA. Therefore, down-regulation of RNA polymerase I transcription in cancer cells is an important anticancer therapeutic strategy. Methods A variety of methods were used, including cloning, expression and purification of protein, electrophoretic mobility shift assay (EMSA), circular dichroic (CD) spectroscopy, CD-melting, isothermal titration calorimetry (ITC), chromatin immunoprecipitation (Ch-IP), RNA interference, RT-PCR, Western blot, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) cell assay. Results Our results showed that 2,4-disubstituted quinazoline derivative Sysu12d could down-regulate c-myc through stabilization of c-myc promoter G-quadruplex, resulting in down-regulation of nucleolin expression. Sysu12d could also disrupt nucleolin/G-quadruplex complex. Both of the above contributed to the down-regulation of ribosomal RNA synthesis, followed by activation of p53 and then cancer cell apoptosis. Conclusions These mechanistic studies set up the basis for further development of Sysu12d as a new type of lead compound for cancer treatment. General significance 2,4-Disubstituted quinazoline derivatives may have multi-functional effect for cancer treatment. [ABSTRACT FROM AUTHOR]

Abstract: The protein POT1 plays an important role in telomere protection, which is related with telomere elongation and cell immortality. The protein has been recognized as a promising drug target for cancer treatment. In the present study, we cloned, overexpressed in Escherichia coli for the first time, and purified recombinant human POT1. The protein was proved to be active through filter binding assay, FRET and CD experiments. In the initial screening for protein binding ligands using SPR, compound Sysu-00692 was found to bind well with the POT1, which was confirmed with EMSA. Its in vivo activity study showed that compound Sysu-00692 could interfere with the binding between human POT1 and the telomeric DNA through chromatin immunoprecipitation. Besides, the compound showed mild inhibition on telomerase and cell proliferation. As we know, compound Sysu-00692 is the first reported POT1-binding ligand, which could serve as a lead compound for further improvement. This work offered a potentially new approach for drug design for the treatment of cancers. [Copyright &y& Elsevier]

A series of acridone-naphthalimide derivatives were synthesized for enhancing anti-cancer activity. Subsequent evaluation showed that derivative WZZ02 could stabilize oncogene PDGFR-β promoter G-quadruplex and destabilize its corresponding i-motif structure resulting in down-regulation of PDGFR-β gene transcription selectively, which caused tumor cells apoptosis. • PDGFR-β is upregulated in various types of cancers and is a known anti-tumor target. • We synthesized and evaluated various fluorescent acridone-naphthalimide derivatives. • WZZ02 selectively stabilized PDGFRβ promoter G-quadruplex and destabilize its i-motif. • WZZ02 down-regulated PDGFR-β gene expression and inhibited cancer cell proliferation. • WZZ02 exhibited tumor growth inhibition activity in MCF-7 xenograft tumor model. Upregulation of platelet-derived growth factor receptor β (PDGFR-β) has been found to be associated with development of various types of cancers, which has become an attractive target for anti-tumor treatment. Previously, we have synthesized and studied an acridone derivative B19 , which can selectively bind to and stabilize oncogene c-myc promoter i-motif, resulting in down-regulation of c-myc transcription and translation, however its effect on tumor cells apoptosis requires improvement. In the present study, we synthesized a variety of B19 derivatives containing a known anti-cancer fluorescent chromophore naphthalimide for the purpose of enhancing anti-cancer activity. After screening, we found that acridone-naphthalimide derivative WZZ02 could selectively stabilize PDGFR-β promoter G-quadruplex and destabilize its corresponding i-motif structure, without significant interaction to other oncogenes promoter G-quadruplex and i-motif. WZZ02 down-regulated PDGFR-β gene transcription and translation in a dose-dependent manner, possibly due to above interactions. WZZ02 could significantly inhibit cancer cell proliferation, and induce cell apoptosis and cycle arrest. WZZ02 exhibited tumor growth inhibition activity in MCF-7 xenograft tumor model, which could be due to its binding interactions with PDGFR-β promoter G-quadruplex and i-motif. Our results suggested that WZZ02 as a dual G-quadruplex/i-motif binder could be effective on both oncogene replication and transcription, which could become a promising lead compound for further development with improved potency and selectivity. The wide properties for the derivatives of 1,8-naphthalimide could facilitate further in-depth mechanistic studies of WZZ02 through various fluorescent physical and chemical methods, which could help to further understand the function of PDGFR-β gene promoter G-quadruplex and i-motif. [ABSTRACT FROM AUTHOR]

Some of the compounds show antiproliferative properties against hepatic carcinoma (HepG2) cells in vitro. [ABSTRACT FROM AUTHOR]