Search

D‐Ring‐seco‐limonoids (tetranortriterpenoids), such as gedunin and xylogranin B display anti‐cancer activity, acting via inhibition of Hsp90 and/or associated chaperon machinery (e.g. p23). Despite this, these natural products have received relatively little attention, both in terms of an enabling synthetic approach (which would allow access to derivatives), and as a consequence their structure–activity relationship (SAR). Disclosed herein is a generally applicable synthetic route to the BCD ring system of the seco‐D‐ring double bond containing limonoids. Furthermore, cell based assays revealed the first skeletal fragment that exhibited inhibition of the p23 enzyme at a level which was equipotent to that of gedunin, despite being much less structurally complex. The first synthetic route to the BCD ring system of the seco‐D‐ring limonoids has been devised. A synthetic intermediate displayed an equipotent p23 enzyme inhibitory effect to that of the more complex gedunin. [ABSTRACT FROM AUTHOR]

The aim of this study is to investigate the antitumor activity and possible molecular mechanism of Phenethyl isothiocyanate (PEITC) against Ehrlich ascites carcinoma in-vivo and in-vitro. In-vivo, ascetic fluid volume, body weight, serum malondialdehyde (MDA) level and total antioxidant capacity (TAC) were determined using Ehrlich ascites carcinoma (EAC) bearing mice. In-vitro, MTT assay was used. RT-PCR was used to investigate role of PEITC in apoptosis by analyzing the expression of Bax, caspase-9, and Bcl-2 genes. The effect of PEITC on caspase-9 enzyme activity was also tested. PEITC and/or Doxorubicin (Dox) treatment significantly suppressed EAC growth as compared to EAC/oil control mice. PEITC treatment showed a dose-dependent inhibition of EAC cells as indicated by MTT assay. We found that significant increase in MDA level and decrease in TAC caused by Dox treatment were significantly reduced by combination with PEITC treatment. Bax, caspase-9 genes' expression and caspase-9 enzymatic activity were significantly increased, while Bcl-2 gene expression was significantly decreased in PEITC treated mice. PEITC may act as a promising anticancer agent either alone or more effectively in combination with Dox through apoptotic cell death induction. [ABSTRACT FROM AUTHOR]

Aim: Hepatocellular carcinoma (HCC) is the fifth most common cancer in men and the seventh in women. HCC varies widely in incidence through the world, with rising incidence in Egypt. This study aimed to estimate the serum levels of matrix metalloproteinase-9 (MMP-9) and its substrate galectin-3 in order to evaluate their diagnostic accuracy and their relation to HCC-related clinical features. Methods: For this purpose, serum levels of these biochemical markers were assessed in 50 HCC patients, 30 cirrhotic patients in addition to 10 healthy subjects as a control group using enzyme linked immune-sorbent assay (ELISA). Results: In the present study, circulating level of galectin-3, MMP-9 increased significantly in HCC as compared to the control group (P = 0.044 and 0.04, respectively). However, no significant difference was observed between cirrhotic and HCC patients (P = 0.231 and 0.193, respectively). Our study found that HCC patients with metastatic spread had a significant elevation of both serum galectin-3 and MMP-9 levels (P = 0.028 and <0.0001, respectively). In addition, galectin-3 level significantly increased in HCC patients with poor prognosis suffering from portal vein invasion (P = 0.014). Moreover, MMP-9 increased significantly with increasing stage of Barcelona-Clinic Liver Cancer Group diagnostic and treatment strategy (P = 0.01).ConclusionMMP-9 and galectin-3 could be used as a guide for prognosis of HCC since they may play a role in HCC progression and metastasis. However, they are not useful markers for HCC diagnosis. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the fifth most common cancer in men and the seventh most common in women. This cancer varies widely in incidence throughout the world, with rising incidence in Egypt. HCC is considered the second most frequent cause of cancer incidence and mortality among men in Egypt. This study aimed to estimate the serum levels of nitric oxide (NO) and glutathione reductase in order to evaluate their role as oxidative status markers in HCC development and progression. For this purpose, serum levels of these parameters were assessed in 50 HCC patients, and 30 cirrhotic patients in addition to 15 healthy subjects as a control group. In the present study, glutathione reductase activity showed a significant increase in HCC as compared to the control group (P= 0.019). On the other hand, no significant difference was observed between the cirrhotic and HCC patients (P= 0.492). Serum NO was significantly higher in patients with HCC than in cirrhotic patients (P= 0.001) or the control group (P= 0.001), with a sensitivity of (74%) and specificity of (88.89%) at a cut-off level of 614.1 μmol/l. While AFP, alphafetoprotein, at a cutoff level of 200 ng/ml had a sensitivity of (52%), the specificity was (100%). Indeed, nitric oxide was high in 62.5% of AFP-negative HCC patients. In conclusion, glutathione reductase has no role in HCC diagnosis. However, nitric oxide is a potential diagnostic marker for HCC. The simultaneous determination of serum nitric oxide and AFP gave significant improvement in the detection of HCC patients compared to that of AFP alone. [ABSTRACT FROM AUTHOR]

• Crocin has chemo-preventive effect against experimentally-induced hepatocarcinogenesis. • Crocin modulated both intrinsic/extrinsic apoptotic pathways. • Crocin increased Nrf2 signaling pathway and HO-1 expression. • Crocin suppressed Keap-1 expression and hepatic content of c-JNK. The results of the current study investigated the chemo-preventive effect of crocin against hepatocarcinogenesis in rats with particular focus on the evaluation of the modulatory impact of crocin on apoptotic and nuclear factor erythroid 2–related factor 2 (Nrf2) signaling pathways. Thioacetamide (TAA) (200 mg/kg, I.P.) was used for experimental induction of hepatocarcinogenesis in rats. Crocin administration significantly attenuated TAA-induced cancerous lesions with concomitant attenuation of impaired liver functions. This was associated with significant enhancement in hepatic Nrf2 and heme oxygenase-1 (HO-1) expression with parallel suppression in Keap-1 expression. Inline, crocin induced a significant improvement in hepatic oxidative status with enhanced antioxidant batteries. Crocin administration significantly suppressed the hepatic content of c-Jun N-terminal kinase (c-JNK) with significant upregulation in TNF-related apoptosis-inducing ligand (TRAIL) and caspase-8 protein expression as well as p53 gene expression; biomarkers of apoptosis. Moreover, hepatic expression of the apoptotic BAX significantly increased and the anti-apoptotic Bcl-2 significantly decreased in the liver specimen; biomarkers of intrinsic apoptosis. In conclusion; crocin attenuates experimentally induced hepato-carcinogenesis via modulation of oxidative/apoptotic signaling. Namely, crocin induced hepatic expression of Nrf2 with downstream modulation of endogenous HO-1 and Keap-1 signaling with modulation of various key players of apoptosis including; c-JNK, p53, TRAIL, caspase-8, BAX, and Bcl-2. [ABSTRACT FROM AUTHOR]

D-Ring-seco-limonoids (tetranortriterpenoids), such as gedunin and xylogranin B display anti-cancer activity, acting via inhibition of Hsp90 and/or associated chaperon machinery (e.g., p23). Despite this, these natural products have received relatively little attention, both in terms of an enabling synthetic approach (which would allow access to derivatives), and as a consequence their structure-activity relationship (SAR). Disclosed herein is a generally applicable synthetic route to the BCD ring system of the seco-D-ring double bond containing limonoids. Furthermore, cell based assays revealed the first skeletal fragment that exhibited inhibition of the p23 enzyme at a level which was equipotent to that of gedunin, despite being much less structurally complex., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)