Search

Artemisinin is a potential anticancer agent with an interesting trioxane sesquiterpene structure. In order to improve the biological activity and metabolic stability of artemisinin, a series of novel ring-contracted artemisinin dimers were synthesized. These dimers were evaluated by MTT assay against six cancer cell lines. Most of the dimmers exhibited improved antiproliferative activities over artemisinin. Especially, compound 8b showed the most pronounced anti-cancer activity for PC12 cancer cells with an IC 50 value of 1.56 μM. Thus, PC12 cancer cells were used to further investigate the mechanism of antiproliferation for this series of compounds. Compound 8b arrested cell cycle at G1 phase and induced cell apoptosis via up-regulation of Bad, Bax, caspase-3 and caspase-9 protein expressions while inhibiting the expression of Bcl-xL. The present studies are the first to synthesize the ring-contracted artemisinin as dimers and show that these dimers have potent anti-tumor activities against several cancer cell lines. [ABSTRACT FROM AUTHOR]

Hypoxia promotes HCC progression and therapy resistance, and there is no systemic treatment for HCC patients after sorafenib resistance. Thus, it is urgent to develop potential therapeutic regimens for HCC patients by targeting hypoxia signaling. In this study, we showed that evodiamine might be a potential therapeutic medicine for HCC by suppressing HIF-1α. In addition, evodiamine could sensitize the anti-HCC effect of vorinostat in HCC cells under hypoxia. Furthermore, evodiamine plus vorinostat accelerated the degradation of HIF-1α in HCC cells under hypoxia. In general, evodiamine might be a potential therapeutic candidate for HCC patients, and evodiamine combining with vorinostat might be an attractive chemotherapy strategy for HCC treatment. [ABSTRACT FROM AUTHOR]

Abstract: The camptothecins, which target the intranuclear enzyme topoisomerase I, have advanced to the forefront of several areas of developmental chemotherapy of cancers. In the present study, we investigated the potential anti-human ovarian cancer effects of NSC606985, a novel and rarely studied camptothecin analog, and its combination with cisplatin (CDDP). Human ovarian cancer cell line COC1 cells were treated with different nanomolar of NSC606985 with or without CDDP, and cell growth and apoptosis were evaluated, respectively, by MTT assay and annexin-V assay on flow cytometry. Chou–Talalay analysis was used to evaluate combined effect of NSC606985 and CDDP. Western blot was used to detect protein kinase Cδ (PKCδ), caspase-3 and hypoxia-inducible factor-1α (HIF-1α) proteins. Our results showed that NSC606985 at nanomolar concentration induced apoptosis with the activation of PKCδ in COC1 cells. Especially, NSC606985 presented the significant combined effects on COC1 cells in terms of growth inhibition and apoptosis induction. In addition, NSC606985 significantly antagonized the accumulation of HIF-1α stabilized by hypoxia or hypoxia-mimetic agent. These results suggest that NSC606985 and its combination with CDDP present the therapeutic potential on ovarian cancer, and deserve further preclinical and clinical studies. [Copyright &y& Elsevier]

Non-small cell lung cancer (NSCLC) is one of the most general malignant tumors. The overexpression of epidermal growth factor receptor (EGFR) is a common marker in NSCLC, and it plays an important role in the proliferation, invasion, and metastasis of cancer cells. At present, drugs developed with EGFR as a target suffer from drug resistance, so it is necessary to study new compounds for the treatment of NSCLC. The active substance in green tea is EGCG, which has anti-cancer effects. In this study, we synthesized dimeric-(−)-epigallocatechin-3-gallate (prodelphinidin B-4-3,3‴-di- O -gallate, PBOG), and explored the effect of PBOG on lung cancer cells. PBOG can inhibit the proliferation and migration of NCI–H1975 cells, promote cell apoptosis, and inhibit cell cycle progression. In addition, PBOG can bind to the EGFR ectodomain protein and change the secondary structure of the protein. At the same time, PBOG decreases the expression of EGFR and downstream protein phosphorylation. Animal experiments confirmed that PBOG can inhibit tumor growth by inhibiting EGFR phosphorylation. Collectively, our study results show that PBOG may induce a decrease in intracellular phosphorylated EGFR expression by binding to the EGFR ectodomain protein, thereby inducing apoptosis and inhibiting cell cycle progression, thus providing a new strategy to treat lung cancer. [Display omitted] • PBOG can inhibit cell proliferation and cell cycle processes，and promote apoptosis. • PBOG may combine with EGFR extracellular domain to change its secondary structure. • PBOG inhibits the phosphorylation of EGFR in NCI–H1975 cells. • PBOG can inhibit tumor growth in vivo by reducing p -EGFR protein. [ABSTRACT FROM AUTHOR]

Tamoxifen (TAM) is frequently used to treat patients with estrogen receptor-positive (ER+) breast cancer; however, the development of endocrine resistance represents a major impediment for successful treatment. Recent studies have demonstrated that long non-coding RNAs (lncRNAs) may serve critical roles in regulating endocrine resistance in breast cancer. In the present study, it was determined that the expression of lncRNA in nonhomologous end joining pathway 1 (LINP1) was increased in tamoxifen-resistant breast cancer cells, and that LINP1 knockdown significantly attenuated the tamoxifen resistance and viability of tamoxifen-resistant breast cancer cells in vitro and in vivo. LINP1 knockdown increased apoptosis in cells following treatment with tamoxifen. Furthermore, LINP1 overexpression resulted in increased cell mobility by regulating the EMT process. Mechanistically, LINP1 is a direct target of ER-mediated transcriptional repression, and both tamoxifen treatment and hormone deprivation increased the expression of LINP1. LINP1 overexpression was associated with downregulation of the levels of ER protein and attenuated the estrogen response, which is a pivotal contributing factor to anti-estrogen resistance. Taken together, the present study highlights the pivotal role of LINP1 in tamoxifen resistance, which may serve as a potential target to improve the effectiveness and efficacy of tamoxifen treatment in breast cancer. • LINP1 is upregulated in tamoxifen resistant breast cancer cells and is correlated with tamoxifen resistance. • LINP1 promotes tamoxifen resistance through regulating proliferation, mobility, and tamoxifen-induced apoptosis. • LINP1 is transcriptionally regulated by ER and LINP1 inhibits ER expression and estrogen signaling. [ABSTRACT FROM AUTHOR]