Cellular alterations and damage to the renal tissue of marine catfish Arius arius following Cd exposure and the possible sequestrant role of Metallothionein.

Cd is a non-degradable heavy metal pollutant with no known biological role. When taken up by living organisms from the environment, it causes extensive tissue damage. Here, we studied the effects of exposure to 20 mg/L-1CdCl2for 0, 24, 48, and 72 h on the renal tissue of marine catfish Arius arius. Cd uptake, metallothionein (MT) induction, microarchitectural alterations, DNA fragmentation, and caspase-3 activity were studied. Cd and MT levels were time-dependent and positively correlated. The diameter of the Bowman's capsule and tubules was significantly increased. Meanwhile, the density, diameter, and volume of the glomerulus as well as the density and volume of tubules decreased. Cd induced apoptosis though elevatedcaspase-3 activity. These results support the notion that exposure to sublethal Cd levels induces oxidative stress, leading to structural and functional impairment of the kidneys. Cd uptake and MT induction can serve as useful environmental biomarkers.

Fungal taxol extracted from Cladosporium oxysporum induces apoptosis in T47D human breast cancer cell line.

PURPOSE: The present study concerns molecular mechanisms involved in induction of apoptosis by a fungal taxol extracted from the fungus Cladosporium oxysporum in T47D human breast cancer cells. MATERIALS AND METHODS: Apoptosis-induced by the fungal taxol was assessed by MTT assay, nuclear staining, DNA fragmentation, flow cytometry and pro- as well as anti-apoptotic protein expression by Western blotting. RESULTS: Our results showed inhibition of T47D cell proliferation with an IC50 value of 2.5 µM/ml after 24 h incubation. It was suggested that the extract may exert its anti-proliferative effect on human breast cancer cell line by suppressing growth, arresting through the cell cycle, increase in DNA fragmentation as well as down-regulation of the expression of NF-?B, Bcl-2 and Bcl-XL and up-regulation of pro-apoptotic proteins like Bax, cyt-C and caspase-3. CONCLUSIONS: We propose that the fungal taxol contributes to growth inhibition in the human breast cancer cell through apoptosis induction via a mitochondrial mediated pathway, with possible potential as an anticancer therapeutic agent.

Molecular mechanism underlying hesperetin-induced apoptosis by in silico analysis and in prostate cancer PC-3 cells.

AIM: To investigate the molecular mechanisms underlying triggering of apoptosis by hesperetin using in silico and in vitro methods. METHODS: The mechanism of binding of hesperetin with NF-?B and other apoptotic proteins like BAX, BAD, BCL2 and BCLXL was analysed in silico using Schrodinger suite 2009. In vitro studies were also carried out to evaluate the potency of hesperetin in inducing apoptosis using the human prostate cancer PC-3 cell line. RESULTS: Hesperetin was found to exhibit high-affinity binding resulting from greater intermolecular forces between the ligand and its receptor NF-?B (-7.48 Glide score). In vitro analysis using MTT assay confirmed that hesperetin reduced cell proliferation (IC50 values of 90 and 40µM at 24 and 48h respectively) in PC-3 cells. Hesperetin also downregulated expression of the anti-apoptotic gene BCLXL at both mRNA and protein levels and increased the expression of pro-apoptotic genes like BAD at mRNA level and BAX at mRNA as well as protein levels. CONCLUSION: The results suggest that hesperetin can induce apoptosis by inhibiting NF-?B.

Anti-cancer effects of thymoquinone in mouse neuroblastoma (Neuro-2a) cells through caspase-3 activation with down-regulation of XIAP.

Thymoquinone (TQ) is a bioactive component derived from the medicinal plant Nigella sativa. Recent studies reported that TQ exhibited cytotoxic effects in several cancer cell lines. Currently, no information in the literature is found concerning its mechanisms and cytotoxicity on neuroblastoma cells. In this study, the cytotoxicity of TQ in mouse neuroblastoma cells (Neuro-2a) was investigated. Our results showed that TQ significantly reduced viability of Neuro-2a cells than normal neuronal cells. Apoptosis induction by TQ was confirmed by DAPI and AO/PI staining. TQ triggered the apoptotic pathway, which was characterized by increased Bax/Bcl-2 ratio. TQ significantly increased the expression of pro-apoptotic protein Bax, whereas decreased the expression of anti-apoptotic protein Bcl-2, which leads to the release of cytochrome c from mitochondria into the cytoplasm. Moreover, TQ treatment directs the activation of caspase-3 followed by the cleavage of poly(ADP-ribose) polymerase (PARP). Interestingly, we also observed that TQ down-regulated caspase inhibitor X-linked inhibitor of apoptosis protein (XIAP). These results indicate that TQ induces apoptosis via caspase-3 activation with down-regulation of XIAP in Neuro-2a cells.