FV peptide induces apoptosis in HEp 2 and HeLa cells: an insight into the mechanism of induction

The present study is an attempt to evaluate the antiproliferative potential of peptide (7.6 kDa) from lionfish (Pterios volitans) venom on cultured HEp2 and HeLa cells. Different dose of purified peptide (1, 2 and 4 μg/ml) at different time points (12, 24 and 36 hrs) were tested for antiproliferative index of the peptide. Among them, 2 μg/ml at 24 hrs was found to effectively inhibit cancer cell growth in vitro and did not cause any adverse effect on normal human lymphocytes. Apoptosis was examined by propidium iodide staining, confirmed by the expression of caspase-8 and caspase-3, down regulation of Bcl-2 expression and DNA fragmentation in treated cells, when compared to untreated HEp2 and HeLa cells. Thus fish venom peptide was found to selectively induce apoptosis in cancer cell

Yokukansan Inhibits Neuronal Death during ER Stress by Regulating the Unfolded Protein Response

Recently, several studies have reported Yokukansan (Tsumura TJ-54), a traditional Japanese medicine, as a potential new drug for the treatment of Alzheimer's disease (AD). Endoplasmic reticulum (ER) stress is known to play an important role in the pathogenesis of AD, particularly in neuronal death. Therefore, we examined the effect of Yokukansan on ER stress-induced neurotoxicity and on familial AD-linked presenilin-1 mutation-associated cell death.We employed the WST-1 assay and monitored morphological changes to evaluate cell viability following Yokukansan treatment or treatment with its components. Western blotting and PCR were used to observe the expression levels of GRP78/BiP, caspase-4 and C/EBP homologous protein.Yokukansan inhibited neuronal death during ER stress, with Cnidii Rhizoma (Senkyu), a component of Yokukansan, being particularly effective. We also showed that Yokukansan and Senkyu affect the unfolded protein response following ER stress and that these drugs inhibit the activation of caspase-4, resulting in the inhibition of ER stress-induced neuronal death. Furthermore, we found that the protective effect of Yokukansan and Senkyu against ER stress could be attributed to the ferulic acid content of these two drugs.Our results indicate that Yokukansan, Senkyu and ferulic acid are protective against ER stress-induced neuronal cell death and may provide a possible new treatment for AD

Ferulic acid and derivatives: molecules with potential application in the pharmaceutical field

Ferulic acid is a phenolic acid widely distributed in the plant kingdom. It presents a wide range of potential therapeutic effects useful in the treatments of cancer, diabetes, lung and cardiovascular diseases, as well as hepatic, neuro and photoprotective effects and antimicrobial and anti-inflammatory activities. Overall, the pharmaceutical potential of ferulic acid can be attributed to its ability to scavenge free radicals. However, recent studies have revealed that ferulic acid presents pharmacological properties beyond those related to its antioxidant activity, such as the ability to competitively inhibit HMG-CoA reductase and activate glucokinase, contributing to reduce hypercholesterolemia and hyperglycemia, respectively. The present review addresses ferulic acid dietary sources, the pharmacokinetic profile, antioxidant action mechanisms and therapeutic effects in the treatment and prevention of various diseases, in order to provide a basis for understanding its mechanisms of action as well as its pharmaceutical potential

PGE from Octopus aegina Induces Apoptosis in Ehrlich’s Ascites Carcinoma of Mice

The present study was carried out to assess the antitumor effect of venomous peptide from the cephalopod Octopus aegina on Ehrlich’s ascites carcinoma (EAC). Male albino Swiss mice were used in the present study. Four groups of animals were treated with three doses of the sublethal dose of venom, 15, 75, and 150 µg/kg body weight (intraperitoneal injection), along with the standard drug 5-fluorouracil (20 mg/kg b.w.). After 10 days of treatment, six animals from each group were sacrificed for the biochemical analysis and the rest were left to calculate the mean survival time. In EAC-bearing mice, mean lifespan, tumor volume, hemoglobin, red blood cells, and lymphocytes were significantly decreased when compared to the normal animals. While body weight, neutrophils, and viable tumor cell count were increased in the EACbearingmice, these changes were brought back to near normal levels in different treatment groups. Themacromolecule concentration of peritoneal cells, such as DNA, RNA, and protein, were altered in the EAC-bearingmice and observed to be near normal in the treatment groups. The caspase-3 activity was significantly increased in the peritoneal cells of the treatment groups when compared to the EAC-bearing mice. The role of apoptotic cascade in EAC cell death was confirmed by the DNA fragmentation on agarose gel. Apart from the antitumor effect, octopus venom reduced the tumor burden on the liver and altered the changes in the activities of alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP). Therefore, the venom from O. aegina has a potential antitumor effect on the EAC-bearing mice

Histopathological changes induced by mice after intramuscular injection of venom from spin-bellied sea snake, Lepemis curtus (Shaw, 1802)

The venom of the Lapemis curtus was tested for its ability to induce histopathological changes in mice intraperitoneal injection of the venom (LD50 of 0.65 mg kg-1), by light microscopic examination of some organs (liver, kidney and spleen). L. curtus veno0m induces changes including necrosis and edematous appearance with cellular infiltration and vacuolation. The injury of kidneys includes significant changes of the glomerular apparatus. Venom trated mice liver shows congestion, micro vesicular fatty changes and infiltration of inflammatory cells around the portal vein. Where as, spleen showed hemorrhage, congested and inflammation were observed. Areas of hemorrhage, vascular congestion and cloudy swelling in renal tubules were observed in the kidney. No myoglobinuria was noted in any group of animals. The crude venom was also administered intraperioteneally into the experimental animals and tissue samples were taken at several time intervals. The venom of the sea snake L. curtus, was tested for its ability to induce myonecrosis changes in albino mice. Induction of myonecrosis was demonstrated by their ability to release Creatine Kinase (CK) from damages muscle fibers and direct histopathological examination of the injected muscles (i.m). Crude venom exhibits intense myonecrosis characterized by the changes including, necrosis and edematous appearance with cellular infiltrate, vacuolation and degenerated muscle cells with delta lesions and heavy edema in between the cells

Inhibition of cancer cell proliferation in vitro and tumor growth in vivo by Hydrophis spiralis sea snake venom

The anti-tumor activity of the sea snake venom (Hydrophis spiralis) was evaluated against Ehrlich’s Ascites Carcinoma (EAC) in Swiss albino mice and HeLa and Hep2 tumor cell cultures. Among the different dose tested 4.18µg mL-1 at 24 h was found to effectively inhibit cancer cell proliferation. The same dose on EAC – bearing mice by i.p. injection significantly reduced the tumor growth and was demonstrated by increased life span of the mice by 182.81%

Antitumor effect of snake venom (Hydrophis spiralis) on Erhlich Ascites Carcinoma bearing mice

The present study was carried out to assess the antitumor effect of venom from snake, Hydrophis spiralis on the Ehrlich Ascites Carcinoma (EAC). Four groups of albino Swiss mice were treated with three doeses of the sub lethal dose of venom, viz., 0.418, 4.18 and 6.29 µg kg-1 body weight (intraperitoneal injection) along with the standard drug 5 flurouracil (20 mg kg-1 b.w.). The biochemical analysis and rest was left to calculate the mean survival time. In EAC bearing mice, mean life span tumor volume, hemoglobin, red blood cell and lymphocytes were significantly decreased when compared to the normal animals. Whereas, body weight, neutrophils and viable tumor cell count was increased in the EAC bearing mice. These changes were brought back to near normal levels in different treatment groups. The caspase 3 activity was significantly increased in the peritoneal cells of the treatment groups when compared to the EAC bearing mice. The role of apoptotic cascade in EAC cell death was confirmed by the DNA fragmentation on agarose gel. Apart from the antitumor effect, snake venom reduced the tumor burden on the liver and altered the changes in the activities of alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP). Hence the venom from H. spiralis has a potential antitumor effet on the EAC bearing mice

Fish venom (Pterios volitans) peptide reduces tumor burden and ameliorates oxidative stress in Ehrlich’s Ascites Carcinoma xenografted mice

The present study was carried out to assess the effect of Pterios volitans venom (mixture of peptides) on Ehrlich’s ascites carcinoma (EAC) and its influence on antioxidant status in the liver. Among six groups of albino mice, three were treated with sublethal doses of venom, along with the standard drug, 5-fluorouracil. In EAC-bearing mice, mean life span and antioxidants were significantly decreased, whereas, body weight, tumor volume, viable tumor cell count, lipid peroxidation and expression of proliferating cell nuclear antigen were significantly increased. These changes were brought back to near normal in treatment groups. The findings are further confirmed by histopathological observations