Latha Periyasamy

BDMC-A, an analog of curcumin, inhibits markers of invasion, angiogenesis, and metastasis in breast cancer cells via NF-κB pathway--A comparative study with curcumin.

Breast cancer chemoprevention has become increasingly important in India as it faces a potential breast cancer epidemic over the next decade. Curcumin, the active ingredient in turmeric is a well known chemopreventive agent that possesses various therapeutic properties including antioxidants and anti-inflammatory effects. In the present study, we have investigated the inhibitory effects of BDMC-A, an analog of curcumin, on invasion, angiogenesis and metastasis markers using in vitro with MCF-7 cells and in silico studies, hence proved that BDMC-A has more potential than curcumin. Mechanistic studies revealed that BDMC-A might have exerted its activity by inhibiting metastatic and angiogenic pathways by modulating the expression of proteins upstream to NF-κB (TGF-β, TNF-α, IL-1β and c-Src), and NF-κB signaling cascade (c-Rel, COX-2, MMP-9, VEGF, IL-8) and by upregulating TIMP-2 levels. An in silico molecular docking study with NF-κB revealed that the docking score and interaction of BDMC-A with NF-κB-DNA binding was more efficient when compared to curcumin. Our overall results showed that BDMC-A more effectively inhibited invasion, angiogenesis and metastasis markers compared to curcumin. The activity can be attributed to the presence of hydroxyl group in the ortho position in its structure. Further research are going on to prove its potential as a therapeutic agent for breast cancer.

Effects of Short Term Exposure of Atrazine on the Liver and Kidney of Normal and Diabetic Rats

The present study evaluates the effects of short term (15 days) exposure of low dose (300 μg kg−1) of atrazine (2-chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine) on antioxidant status and markers of liver and kidney damage in normal (nondiabetic) and diabetic male Wistar rats. Rats were divided into four groups: Group I as normal control, Group II as atrazine treated, Group III as diabetic control, and Group IV as atrazine treated diabetic rats. Atrazine administration resulted in increased MDA concentration as well as increased activities of SOD, CAT, and GPx in both liver and kidney of atrazine treated and atrazine treated diabetic rats. However, GSH level was decreased in both liver and kidney of atrazine treated and atrazine treated diabetic rats. Atrazine administration led to significant increase in liver damage biomarkers such as AST, ALT, and ALP as well as kidney damage biomarkers such as creatinine and urea in both normal and diabetic rats, but this increase was more pronounced in diabetic rats when compared to normal rats. In conclusion, the results of the present study demonstrate that short term exposure of atrazine at a dose of 300 μg kg−1 could potentially induce oxidative damage in liver and kidney of both normal and diabetic rats.

Targeting P-glycoprotein: Investigation of piperine analogs for overcoming drug resistance in cancer

P-glycoprotein (P-gp) is a drug transporter that effluxes chemotherapeutic drugs and is implicated in the development of resistance of cancer cells to chemotherapeutic drugs. To date, no drug has been approved to inhibit P-gp and restore chemotherapy efficacy. Moreover, majority of the reported inhibitors have high molecular weight and complex structures, making it difficult to understand the basic structural requirement for P-gp inhibition. In this study, two structurally simple, low molecular weight piperine analogs Pip1 and Pip2 were designed and found to better interact with P-gp than piperine in silico. A one step, acid-amine coupling reaction between piperic acid and 6,7-dimethoxytetrahydroisoquinoline or 2-(3,4-dimethoxyphenyl)ethylamine afforded Pip1 and Pip2, respectively. In vitro testing in drug resistant P-gp overexpressing KB (cervical) and SW480 (colon) cancer cells showed that both analogs, when co-administered with vincristine, colchicine or paclitaxel were able to reverse the resistance. Moreover, accumulation of P-gp substrate (rhodamine 123) in the resistant cells, a result of alteration of the P-gp efflux, was also observed. These investigations suggest that the natural product analog – Pip1 ((2E,4E)-5-(benzo[d][1,3]dioxol-5-yl)-1-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1 H)-yl)penta-2,4-dien-1-one) – is superior to piperine and could inhibit P-gp function. Further studies are required to explore the full potential of Pip1 in treating drug resistant cancer.

In Silico and In Vitro Investigation of the Piperineʼs Male Contraceptive Effect: Docking and Molecular Dynamics Simulation Studies in Androgen-Binding Protein and Androgen Receptor

Understanding the molecular mechanism of action of traditional medicines is an important step towards developing marketable drugs from them. Piperine, an active constituent present in the Piper species, is used extensively in Ayurvedic medicines (practiced on the Indian subcontinent). Among others, piperine is known to possess a male contraceptive effect; however, the molecular mechanism of action for this effect is not very clear. In this regard, detailed docking and molecular dynamics simulation studies of piperine with the androgen-binding protein and androgen receptors were carried out. Androgen receptors control male sexual behavior and fertility, while the androgen-binding protein binds testosterone and maintains its concentration at optimal levels to stimulate spermatogenesis in the testis. It was found that piperine docks to the androgen-binding protein, similar to dihydrotestosterone, and to androgen receptors, similar to cyproterone acetate (antagonist). Also, the piperine-androgen-binding protein and piperine-androgen receptors interactions were found to be stable throughout 30 ns of molecular dynamics simulation. Further, two independent simulations for 10 ns each also confirmed the stability of these interactions. Detailed analysis of the piperine-androgen-binding protein interactions shows that piperine interacts with Ser42 of the androgen-binding protein and could block the binding with its natural ligands dihydrotestosterone/testosterone. Moreover, piperine interacts with Thr577 of the androgen receptors in a manner similar to the antagonist cyproterone acetate. Based on the in silico results, piperine was tested in the MDA-kb2 cell line using the luciferase reporter gene assay and was found to antagonize the effect of dihydrotestosterone at nanomolar concentrations. Further detailed biochemical experiments could help to develop piperine as an effective male contraceptive agent in the future.

Antibacterial applications of α-Fe2O3/Co3O4 nanocomposites and study of their structural, optical, magnetic and cytotoxic characteristics

Owing to their multiple mechanisms of bactericidal activity, inorganic metal oxides and hybrid metal oxide nanocomposites may serve as a new class of effective disinfectants. Among metal oxide nanoparticles, iron oxide nanoparticles exhibit minimal or no cytotoxicity to human cells with very efficient bactericidal properties over a wide spectrum of bacteria. This paper presents the very first report on antibacterial properties of novel nanocomposites of iron oxide and cobalt oxide nanoparticles against pathogenic bacterial strains B. subtilis, S. aureus, E.coli and S. typhi. The enhanced bactericidal activity of the Fe/Co oxide nanocomposite was the result of synergistic effect of iron oxide and cobalt oxide nanoparticles. The nanocomposites were synthesized using co-precipitation route with increasing cobalt content in the sample and further characterized using XRD, TEM, Raman and VSM to investigate structural, optical and magnetic properties of the prepared nanocomposites, respectively. Also, the prepared nanocomposites were highly biocompatible and found non-toxic to human cell line MCF7.

One-pot microwave-assisted in situ reduction of Ag+ and Au3+ ions by Citrus limon extract and their carbon-dots based nanohybrids: a potential nano-bioprobe for cancer cellular imaging

In the present study, we demonstrate a rapid, in situ reduction of metal (Ag+ and Au3+) ions and subsequent carbonization of Citrus limon (lemon) extract to synthesize highly luminescent carbon-dots (C-dots) and their metal nanohybrids (MCNs) using one-pot microwave (MW) assisted technique within 6 min. In principle, L-ascorbic acid, citric acid and flavonoids reduce metal ions into corresponding metal nanoparticles followed by carbonization of carbohydrates in the lemon extract along with externally added ethylenediamine (EDA) to form EDA-functionalized C-dots based nanohybrids. The synthesized pristine C-dots, Ag/C-dot and Au/C-dot nanohybrids (<5 nm) colloidal solution exhibited bright photoluminescence (PL) at ∼515 nm with significant quantum yield (QY) of 48.3%, 46.2%, 62.2% and PL emission lifetime of 3.6 ns, 9.4 ns and 9.0 ns respectively. The reduced PL intensity and QY for Ag/C-dot nanohybrids could be due to fluorescence resonance energy transfer (FRET) while enhanced PL intensity and QY for Au/C-dot nanohybrids could be attributed to surface plasmonic resonance (SPR), when compared to pristine C-dots. These C-dots-based nanohybrids exhibited no signs of cytotoxicity in colon cancer cell lines (SW-480) and were easily internalized for fluorescence bioimaging. Thus, the MW-assisted sustainable synthesis of pristine C-dots and metal/C-dot nanohybrids derived from natural lemon extract can be exhibited as eco-friendly intense potential nano-bioprobes for cancer cellular imaging applications.

Reversible testicular toxicity of piperine on male albino rats

Background: Piperine was widely used in traditional medicine for inducing sterility and abortion. Objective: To evaluate the effect of the piperine on testis of male albino rats. Materials and Methods: Adult male rats were divided into four groups (n = 12). Group I (control): Rats were given vehicle p.o. i.e. 0.5% carboxymethyl cellulose in normal saline daily for 60 days, Group II (ED): Rats received piperine at a dose of 10 mg/kg body weight (b.w.) daily, Group III (E4D): Rats received piperine at a dose of 10 mg/kg b.w. on every 4th day, Group IV (E7D): Rats received piperine at a dose of 10 mg/kg b.w. on every 7th day. Half of the animals from each group were sacrificed after the treatment period (60 days), and the remaining were kept for drug-free withdrawal period (60 days) and then sacrificed. Results: Piperine significantly decreased the reproductive organ weights in groups ED and E4D. Piperine induced hormonal imbalance by altering the serum levels of follicle-stimulating hormone, luteinizing hormone, sex hormone binding globulin, serum, and testicular testosterone in groups ED and E4D. Furthermore, piperine decreased the activity of germ cell markers and Leydig cellular steroidogenic enzymes in the groups ED and E4D after 60 days. All the above-altered values returned to normal levels after withdrawal period. Histopathological findings also supported the above findings. Conclusion: From the above data, it can be concluded that piperine could be a good lead molecule for the development of reversible oral male contraceptive.

Effects of Atrazine on Reproductive Health of Nondiabetic and Diabetic Male Rats

The aim of the present study was to investigate the effects of low dose of atrazine on reproductive system of male Wistar rats. 16 rats were divided into four groups of four animals each. Group I (nondiabetic) and group III (diabetic) animals served as controls that received safflower oil (300 μL/kg bw/day), respectively. Group II (nondiabetic) and group IV (diabetic) animals received atrazine (300 μg/kg bw/day). Nonsignificant decrease in the activities of antioxidant and steroidogenic enzymes and sperm parameters suggests that atrazine did not produce any effect on reproductive system of rats. Histological findings also revealed that atrazine at a dose of 300 μg/kg bw did not produce any testicular toxic effects in nondiabetic and diabetic atrazine treated rats. Low dose of atrazine did not show reproductive toxicity in rats. To know the effects of atrazine in diabetic rats further studies have to be carried out with increased concentration of atrazine.

Bixin Triggers Apoptosis of Human Hep3B Hepatocellular Carcinoma Cells: An Insight to Molecular and IN SILICO Approach

Abstract Hepatocellular carcinoma (HCC) is the most common liver cancer and is known to be resistant to conventional chemotherapy. The use of herbal medicine and supplements has increased over recent decades following side effects and resistant to conventional chemotherapy. The seeds of Bixa orellana L. commonly known as annatto have recently gained scientific attention due to presence of a carotenoid bixin for its substantial anticancer properties. However, molecular mechanisms underlying bixin-induced apoptosis are still unclear. Treatment of bixin significantly decreased the number of Hep3B cells and morphological study revealed the change in cellular and nuclear morphology that trigger the events of apoptosis confirmed by annexin V/PI staining. Further DCFDA and rhodamine 123 spectrofluorimetry study showed elevation in reactive oxygen species (ROS) production and loss of mitochondrial membrane potential (MMP), respectively. ROS production caused DNA damage and apoptosis was marked by cell cycle arrest, up-regulation of Bax and FasL protein as well as cleavage of caspase-9, caspase-8 and caspase-3 protein. Docking study with pro-apoptotic molecule Bax and surface Fas ligand exhibited energetically favourable binding interaction. Collectively, these results suggest that bixin capable of modulating the extrinsic and intrinsic molecules of apoptosis indicating its potential for development of promising candidate for hepatocellular carcinoma.

Quercetin enhances stress resistance in Saccharomyces cerevisiae tel1 mutant cells to different stressors

The Saccharomyces cerevisiae TEL1 gene is an ortholog of the human ATM (Ataxia telangiectasia mutated) gene. S. cerevisiae tel1 mutant (tel1∆) lacking Tel1p, share some of the cellular defects with ATM mutation that includes prevention of oxidative damage repair, premature aging and apoptosis. In the present study, we investigated the protective effects of quercetin on the sensitivity of yeast S. cerevisiae tel1∆ cells exposed to oxidative, apoptotic and DNA damaging stress and viability of tel1∆ cells during chronological aging. Quercetin improved the stress resistance of tel1∆ cells when challenged with oxidants such as hydrogen peroxide (H2O2), menadine bisulphite (MBS) and tertiary butyl hydroperoxide (t-BHP) by scavenging reactive oxygen species (ROS). Quercetin protected the tel1∆ cells from acetic acid-induced apoptotic cell death and sensitivity against hydroxyurea. We found that quercetin attenuated ROS accumulation and apoptotic markers in tel1∆ cells and therefore an increase in cell viability during chronological aging. Our results from the S. cerevisiae model, suggest that use of quercetin as a food supplement might alleviate oxidative stress mediated DNA damage, apoptosis and age related damaging effects in AT patients and also improve health beneficial effects in humans.