Bacterial and viral vectors as vaccine delivery vehicles for breast cancer therapy.

Breast cancer is the frequently diagnosed cancer among women and it is the most lethal malignancy in women globally. With one million cases every year, breast cancer is the fast-growing cancer type that has a high prevalence rate in young women. The limitations and undesirable side effects of conventional therapies like chemotherapy and radiotherapy on malignant tumors necessitate the development of alternative therapeutic approaches. Gene therapy has emerged as a promising approach to cure a variety of malignant cancer types which involves the delivery of functional gene directly into the target tumor tissue. Efficient gene therapy approach relies on the effective delivery of therapeutic genes to the desired cell type. In this regard, biological and non-biological gene delivery vectors are used to protect the naked foreign DNA to mediate effective tissue entry of the desired gene of interest. In this review, the use of bacterial and viral vectors for breast cancer gene therapy was summarized.

Tinospora cordifolia extract prevents cadmium-induced oxidative stress and hepatotoxicity in experimental rats.

BACKGROUND: Cadmium (Cd) pollution is of serious concern due to its toxic effects in both humans and animals. The study investigates the protective effect of Tinospora cordifolia stem methanolic extract (TCME) on Cd induced hepatotoxicity. OBJECTIVE(S): The objective of the study was to explore the hepatoprotective effects of T. cordifolia extract. MATERIALS AND METHODS: Rats were administered orally with Cd (5 mg/kg) and TCME (100 mg/kg) for 28 days. At the end of the treatment period, serum and liver tissues homogenates were subjected to biochemical analysis. RESULTS: Cd treated rats showed increased activities of the serum marker enzymes of liver damage such as AST and ALT along with increased levels of LPO and protein carbonyl content in liver tissues. Cd treatment also leads to decreased activities of endogenous antioxidants (SOD, CAT, GSH, GPx and GST), membrane ATPases (Na+K+ATPase, Ca2+ATPase and Mg2+K+ATPase) and the tissue glycoprotein levels (hexose, fucose, hexosamine and sialic acid). Histological analysis revealed vacuolar degeneration of hepatocytes with focal necrosis upon Cd administration. TCME co-treatment restored the biochemical and histological alterations caused by Cd intoxication to near normal levels. CONCLUSION: The results of the present investigation reveal the hepatoprotective nature of T.cordifolia against Cd induced hepatotoxicity.

Neferine ameliorates cardiomyoblast apoptosis induced by doxorubicin: possible role in modulating NADPH oxidase/ROS-mediated NFκB redox signaling cascade.

Doxorubicin (DOX) mediated cardiomyopathy is a major challenge in cancer chemotherapy. Redox-cycling of doxorubicin by flavoenzymes makes the heart more vulnerable to oxidative stress leading to cardiac dysfunction. The present study evaluates the role of neferine, a bisbenzylisoquinoline alkaloid, in curbing the molecular consequences of DOX-exposure in H9c2 cardiomyoblasts. Neferine pre-treatment increased cell viability upon DOX-exposure. DOX activates NADPH oxidase subunits, (p22phox, p47phox, gp91phox) as the primary event followed by peak in [Ca2+]i accumulation by 2 h, ROS by 3 h and activated ERK1/2 and p38 MAPKinases, time dependently along with the activation and translocation of NFκB and up-regulated COX2 and TNF-α expressions. Neferine pre-treatment modulated NADPH oxidase/ROS system, inhibited MAPKinases and NFκB activation, reduced sub G1 cell population and concomitantly increased cyclin D1 expression reducing DOX-mediated apoptosis. The study demonstrates for the first time, the molecular sequential events behind DOX toxicity and the mechanism of protection offered by neferine with specific relevance to NADPH oxidase system, MAPKinases, inflammation and apoptosis in H9c2 cells. Our data suggests the use of neferine as a new approach in pharmacological interventions against cardiovascular disorders as secondary complications.

Piperine modulates isoproterenol induced myocardial ischemia through antioxidant and anti-dyslipidemic effect in male Wistar rats.

Myocardial infarction due to ischemia accounts for majority of deaths among cardiovascular disorders. Isoproterenol (ISO) induced myocardial infarction and the protection offered by piperine was investigated in the present report. Lipid profile analysis by determining the levels of cholesterol, phospholipids, triglycerides and lipoproteins in serum and heart tissues showed anti-dyslipidemic action of piperine against ISO induced myocardial injury by modulating the ISO induced altered lipid profiles, maintaining to near control values. ISO treatment increased TBARS levels, PCC, serum markers of heart, depleted antioxidant status (GSH, SOD, CAT, GPx and GST) in tissues and, total, protein- and non-protein-sulfhydryl levels in serum and heart tissues. Piperine pre-treatment decreased the levels of serum markers, lipid peroxidation and PCC with increased antioxidant status in the heart tissues of ISO administered rats. Increased levels of the glycoprotein components in serum and decreased levels in heart tissues upon ISO administration were restored to near normal levels by piperine pre-treatment. Our present reports also showed the modulatory effect of piperine on membrane bound ATPase's showing protection against ISO induced changes in membrane fluidity. The present study proved piperine as a potent therapeutic agent with its antioxidant and anti-dyslipidemic action against ISO induced myocardial infarction.

Neferine from Nelumbo nucifera modulates oxidative stress and cytokines production during hypoxia in human peripheral blood mononuclear cells.

Neferine, an alkaloid from N. nucifera has a broad range of pharmacological activity. Hypoxia mediated stress is involved in the generation of inflammatory responses and cell death. The present study evaluated the protective effect of neferine against hypoxia-induced cytotoxicity, oxidative stress and inflammatory response in human Peripheral Blood Mononuclear Cells (hPBMC). Cytotoxicity, as determined by MTT, LDH and NO assays revealed that 24h of hypoxic exposure results in 20% cell death (IC20) and compromising of cellular integrity, which was restored to near control values by pretreatment with neferine. Oxidative stress parameters such as lipid peroxidation and antioxidant enzymes indicated that neferine exerted a protective effect on hypoxia-induced oxidative stress. Hypoxia-induced Tumor Necrosis Factor-α (TNF-α), Interleukin 6 (IL-6), and Interleukin 8 (IL-8) release were significantly reduced in the neferine pretreated samples indicating its anti-inflammatory role. Our results demonstrate for the first time that neferine exerts a cytoprotective effect against hypoxia-induced oxidative stress and inflammation in hPBMC.

Tinospora cordifolia extract attenuates cadmium-induced biochemical and histological alterations in the heart of male Wistar rats.

Persistence of cadmium (Cd) in the environment causes serious ecological problems. Tinospora cordifolia is a medicinal herb used in Ayurveda for treating various metabolic disorders and toxic conditions. The present study investigates the protective effect of T. cordifolia stem methanolic extract (TCME) on a heavy metal, Cd-induced cardiotoxicity in male Wistar rats. Male albino Wistar rats were divided into four groups (n=6). The animals after treatment for 28days with Cd and TCME were analysed for biochemical and histological changes in the serum and heart tissues. Cd induced lipid peroxidation and protein carbonylation was significantly reduced by TCME. TCME also reduced the histological alterations induced by Cd treatment in the heart tissues with diminished loss of myocardial fibers. Administration of TCME effectively prevented the altered levels of serum marker enzymes (creatine kinase and lactate dehydrogenase), antioxidants, such as superoxide dismutase, catalase, glutathione, glutathione peroxidase and glutathione-S-transferase, and glycoproteins contents such as hexose, hexoseamine, fucose, and sialic acid by Cd intoxication. TCME also offered protection against the change in levels of Na+K+ATPase, Mg2+ATPase and Ca2+ATPase activities against Cd toxicity. The study suggests TCME as a potent cardioprotective agent against Cd induced toxicity.

Modulatory effect of Tinospora cordifolia extract on Cd-induced oxidative stress in Wistar rats.

BACKGROUND: Cadmium (Cd), a nonessential heavy metal, is a major environmental and public health concern. Oxidative stress plays an important role in Cd-induced kidney dysfunction. Tinospora cordifolia, a medicinal plant rich in phytochemicals, possesses antioxidant activity. The objective of the present study was to assess the protective effect of Tinospora cordifolia-stem methanolic extract (TCE) on Cd-induced nephrotoxicity in Wistar rats. METHODS: Male Wistar rats were administered ∼5 mg/kg body weight Cd orally and 100 mg/kg body weight TCE for 28 days. At the end of Cd and TCE treatment, biochemical assays were performed in serum and tissue homogenate. RESULTS: Cd-induced oxidative stress in the kidney resulted in increased levels of lipid peroxidation and protein carbonyl content with a significant decrease in cellular antioxidants, such as reduced GSH, SOD, CAT, GPX, and GST. Cd-induced nephrotoxicity was further confirmed by marked changes in the histology of the kidney and increased levels of kidney markers. Additionally, Cd-treated rats showed alterations in membrane-bound ATPase activity and decreased levels of tissue glycoproteins. Cotreatment with TCE considerably reduced the biochemical alterations in serum and renal tissue induced by Cd, and also restored ATPase activity and glycoproteins to near normal levels. CONCLUSION: Our results suggested that TCE with its antioxidant effect offered cytoprotection against Cd-induced toxicity in kidneys by restoring the altered cellular antioxidants and renal markers. TCE treatment for 28 days reversed ATPase activity and tissue glycoprotein levels. These results revealed the protective effect of TCE on Cd-induced toxicity in kidneys and oxidative stress.

Neferine prevents autophagy induced by hypoxia through activation of Akt/mTOR pathway and Nrf2 in muscle cells.

We have previously reported the prevention of Hypoxia mediated apoptosis by Neferine, an alkaloid from Nelumbo nucifera. The present study was designed to assess the role of neferine in modulation of hypoxia induced autophagy in muscle cells. Cytoprotective dose of neferine in muscle cells (Rhabdomyosarcoma cells) exposed to hypoxia was determined by MTT assay. Hypoxia induced oxidative stress in muscle cells by enhancing lipid peroxidation and depleting cellular antioxidant enzymes. The inhibition of PI3K/Akt/mTOR cell survival signaling acts as a trigger for the hypoxia induced Autophagy. Hypoxia exposure in muscle cells resulted in acidic vesicular formation, as studied by acridine orange staining which serves as an indicator of autophagosome formation. Pretreatment with neferine inhibited autophagy induction by activating Akt/mTOR pathway and down regulating Beclin 1, PI3KCIII and LC3B-II in cells exposed to hypoxia. Further, Neferine also modulated hypoxia mediated changes in the cellular antioxidant levels by Nrf2 nuclear translocation. Collectively, results of the study suggest the role of neferine in preventing hypoxia induced autophagy in muscle cells.