To explore the potential anti-tumour activities of xanthone derivatives, 26 hydroxylxanthones and benzoxanthones and their structurally modified analogues were examined for potential cytotoxic activities against eight human cancer cell lines. Most of the xanthone derivatives exhibited a higher degree of cytotoxicity on HepG2 cells than on the other seven cancer cell lines. Compound 24 (1,3,7-Trihydroxy-12H-benzo[b] xanthen-12-one) showed the highest degree of cytotoxicity of the tested compounds against HepG2 cells and demonstrated good tumour specificity by exhibiting a much higher degree of cytotoxicity against HepG2 cells than against normal liver cells (L02). Several valuable structure-activity relationships were derived from the cytotoxicity data. In addition, we found that compound 24 could downregulate the expression of the Mcl-1 protein, induce changes in the mitochondrial membrane potential and induce apoptosis in HepG2 cells via the mitochondrial pathway. Compound 24 was also shown to inhibit topoisomerase (topo) II activity and downregulate the levels of both topo II mRNA and protein in HepG2 cells. The present results suggest that due to its potent cytotoxicity and good tumour selectivity, compound 24 may be exploited as a potential lead compound in the development of a new anti-tumour agent with specific activity against liver cancer.

Vascular disrupting agents (VDAs) have emerged as a new kind of anti-cancer drug in recent years. Structural modification of an active parent compound is an effective approach to developing new agents with more activity and fewer adverse reactions. In our study, six synthesized stilbene derivatives were screened for their cytotoxic activity against human tumor cells, and their mechanisms of action were investigated. The MTT assay was used to determine the anti-proliferative activity of these compounds. Polymerization of tubulin was detected by a tubulin assembly assay, and the cellular microtubule network was observed by immunocytochemical analyses. Cell-cycle distribution was detected by flow cytometry. A nude mouse model with xenografted colon cancer was used to demonstrate the in vivo anti-tumor activity, and microvessel density (MVD) was determined by immunohistochemistry. The expression levels of protein and mRNA were detected by Western blot and RT-PCR, respectively. Among the six newly synthesized compounds, (Z)-3,4',5-trimethoxylstilbene-3'-O-phosphate disodium (M410) showed potent cytotoxic activity toward proliferating tumor cells and exhibited a similar cytotoxicity against multi-drug resistant (MDR) tumor cells. M410 inhibited bovine brain tubulin polymerization in a way similar to that of colchicine. In proliferating human umbilical vein endothelial cells (HUVECs), 20 nM of M410 induced cellular tubulin depolymerization within 4 h, which led to M phase arrest. Systemic administration of M410 at nontoxic doses in nude mice resulted in inhibition of tumor growth of human colon cancer LoVo xenografts. The tumor vessel density also decreased after M410 treatment, as determined by immunohistochemical staining for CD31. M410 downregulated hypoxia-inducible factor-1 alpha (HIF-1α) expression, reduced nuclear HIF-1α, and downregulated vascular endothelial cell growth factor (VEGF) mRNA. Our results indicate that M410 is a potent microtubule inhibitor that is cytotoxic, angiogenesis inhibiting and vascular targeting.

Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase and a key element in the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. Moreover, it is a negative regulator of autophagy and acts as a central regulator in cell growth. For the treatment of cancer, mTOR is a novel and validated therapeutic target. Previous studies have shown that Akt is frequently activated in nasopharyngeal carcinoma (NPC) tissues; thus, the inhibition of mTOR may be a treatment strategy for this tumor type. To evaluate the effect of the mTOR inhibitor RAD001 on NPC cell lines, we performed 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1) assays, lactate dehydrogenase (LDH) assays, western blotting and flow cytometry to evaluate the mechanisms of cell death. The growth of both CNE-1 and HONE-1 cells was inhibited in a time- and dose-dependent manner. CNE-1 was more sensitive, with a 50% growth inhibition (GI50) of 30.0±1.0 µM compared to HONE-1, cells which had a GI50 of 56.9±13.1 µM. RAD001 induced apoptosis and autophagy in both cell lines. RAD001 induced a significant increase in growth inhibition in the two cell lines when used in combination with the autophagy inhibitor, 3-methyladenine; however, the percentages of apoptotic cells decreased when RAD001 was combined with the caspase inhibitor, z-VAD-fmk. In conclusion, the main mechanism of the mTOR inhibitor RAD001 in these two NPC cells was apoptotic, not autophagic cell death. The combination of RAD001 with autophagy inhibitors may be a useful therapeutic strategy for nasopharyngeal carcinoma.

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Purpose: Anastomotic leakage is one of the most common complications of esophagectomy, it serves as one of the main causes of postoperative death of esophageal cancer. It is of clinical significance to try to discover the risk factors that cause anastomotic leakage.Methods: This retrospective study was conducted on 1,257 consecutive esophageal cancer patients who underwent esophagectomy with intrathoracic anastomosis from January 2010 to December 2015 at a high volume cancer center. Multivariate Logistic Regression analysis, Spearman rank correlation analysis, Mann-Whitney U test and Kruskal-Wallis test were performed to identify the risk factors to the occurrence of anastomotic leakage and the length of hospital stay.Results: Intrathoracic anastomotic leakage occurred in 98 patients (7.8%). Older patients were more likely to develop anastomotic leakage. Patients with diabetes had a higher leakage rate. Intrathoracic anastomotic leakage, old age as well as comorbidities were associated with longer hospital stay.Conclusion: Our study suggested that old age and diabetes were risk factors to intrathoracic anastomotic leakage. In-hospital stay would be lengthened by intrathoracic anastomotic leakage, old age and comorbidities.