Varinder Kaur

Phytoconstituents as apoptosis inducing agents: strategy to combat cancer.

Advancement in the field of cancer molecular biology has aided researchers to develop various new chemopreventive agents which can target cancer cells exclusively. Cancer chemopreventive agents have proficiency to inhibit, reverse and delay process of carcinogenesis during its early and later course. Chemopreventive agents can act as antioxidative, antimutagenic/antigenotoxic, anti-inflammatory agents or via aiming various molecular targets in a cell to induce cell death. Apoptosis is a kind of cell death which shows various cellular morphological alterations such as cell shrinkage, blebbing of membrane, chromatin condensation, DNA fragmentation, formation of apoptotic bodies etc. Nowadays, apoptosis is being one of the new approaches for the identification and development of novel anticancer therapies. For centuries, plants are known to play part in daily routine from providing food to management of human health. In the last two decades, diverse phytochemicals and various botanical formulations have been characterized as agents that possess potential to execute cancer cells via inducing apoptosis. Data obtained from the research carried out globally pointed out that natural products are the potential candidates which have capability to combat cancer. In the present review, we surveyed literature on natural products which throws light on the mechanism through which these phytochemicals induce apoptosis in cancer cells.

Sonochemical synthesis, characterization, antimicrobial activity and textile dyeing behavior of nano-sized cobalt(III) complexes.

Using ultrasonic irradiations, nano-sized cobalt(III) coordination complexes, [Co(NH3)6]Cl3·2H2O (A), [Co(en)3]Cl3·3H2O (B) (en-ethylenediamine) and [Co(dien)2]Cl3·3.5H2O (C) (dien-diethylenetriamine) were synthesized. These complexes were characterized by spectroscopic studies like IR, UV/Visible and NMR. Morphology of these complexes was determined by SEM and particle size with the help of TEM & Zeta-sizer. The comparative thermal stability along with phase difference between nano structures and their respective bulk complexes has been studied by thermal gravimetric analysis (TGA) and X-ray powder diffraction (XRD) study respectively. The dyeing behavior of nano-sized Co(III) complexes and their respective bulks has also been studied (using both exhaust and pad dyeing methods) on cotton and wool fabrics and results shown rationalized dyeing behavior. All these complexes were further tested for antimicrobial activity (against B. subtilis, E. coli, K. pneumoniae, F. oxysporum and A. alternate) and it was observed that nano sized complexes enhanced the activity further.

Pharmacotherapeutic potential of phytochemicals: Implications in cancer chemoprevention and future perspectives

Cancer is a leading cause of disease burden throughout the world. Many cancers develop as a result of exposure to both lifestyle and environmental factors that are potentially modifiable. In the last few years, much of the scientific attention has drawn to the discovery of new and effective chemopreventive agents from natural sources. A multitude of phytoconstituents have been explored for their potential to prevent the occurrence of carcinogenesis both in vitro and in vivo by means of diverse cellular and molecular approaches. Key focus of this review is to highlight some significant and new information about different molecular aspects of chemopreventive ability of plant based phytochemicals in terms of their inhibitory potential on cancer growth. In addition, information regarding certain limiting factors such as whole animal physiology, tumour microenvironment and bioavailability of active components of phytoconstituents used in pre/clinical trials are further explored. This review would further assist the scientific community involved in designing efficacious chemopreventive approaches using these phytochemicals in treating cancer.

Inhibitory Activities of Butanol Fraction from Butea monosperma (Lam.) Taub. Bark Against Free Radicals, Genotoxins and Cancer Cells

The present study was undertaken to investigate antioxidant, antigenotoxic, and antiproliferative activity of butanol fraction (Bmbu) from bark of medicinal plant Butea monosperma. Antioxidant potency of Bmbu was examined by various in vitro assays. It was also investigated for antigenotoxic activity using Escherichia coli. PQ37 employing SOS chromotest. Further, cytotoxic and apoptosis inducing activity of Bmbu was evaluated in MCF‐7 breast cancer cells. Bmbu showed potent free radical scavenging ability in ABTS assay (IC50 56.70 μg/ml) and anti‐lipid peroxidation ability (IC50 40.39 μg/ml). 4NQO and H2O2 induced genotoxicity was suppressed by Bmbu in SOS chromotest by 74.26% and 82.02% respectively. It also inhibited the growth of MCF‐7 cells with GI50 value of 158.71 μg/ml. Induction of apoptosis in MCF‐7 cells by Bmbu treatment was deciphered using confocal microscopy, flow cytometry, and neutral comet assay. Bmbu treatment increased cell population in sub‐G1 phase (69.6%) indicating apoptotic cells. Further, Bmbu treatment resulted in increased reactive oxygen species generation and decreased mitochondrial membrane potential indicating involvement of mitochondrial dependent pathway of apoptosis. HPLC profiling showed the presence of polyphenols such as ellagic acid, catechin, quercetin, and gallic acid as its major constituents. Consequently, it is suggested that the phytoconstituents from this plant may be further exploited for development of novel drug formulation with possible therapeutic implication.

Hepatoprotective activity of Butea monosperma bark against thioacetamide-induced liver injury in rats.

For thousands of years, the plant-based natural products have been a source of curative agents for various ailments. Butea monosperma (Fabaceae) has an important place in Indian traditional system of medicine for curing number of disorders. The present study deals with evaluation of hepatoprotective properties of ethyl acetate fraction (Beac) from B. monosperma bark in rat model. In preliminary antioxidant studies, Beac demonstrated pronounced superoxide scavenging (IC50 88.85μg/ml) and anti-lipid peroxidation (IC50 131.66μg/ml) potential. In animal studies, Beac showed protective effect against thioacetamide-induced pathophysiology in liver of male Wistar rats. The levels of different parameters related to hepatic functions were altered by thioacetamide treatment (300mg/g bw) in rats. The pre-treatment of rats with Beac (50, 100 and 200mg/kg bw) was able to normalize the biochemical markers viz. serum bilirubin, SGOT, SGPT, albumin and ALP along with liver antioxidative molecules viz. SOD, CAT, GSH and GR. Results of histopathological and colorimetric studies revealed that Beac treatment also restored the markers of fibrosis i.e. collagen and hydroxyproline towards normal level. Beac considerably inhibited thioacetamide-induced expression of p-PI3K, p-Akt and p-mTOR in hepatocytes as revealed from immunohistochemical studies. This finding is the first evidence of inhibitory action of B. monosperma bark on these pro-carcinogenic proteins. HRMS analysis revealed the presence of quercetin, buteaspermin B and ononin in Beac fraction of Butea monosperma. From the results, it can be concluded that B. monosperma bark is a rich source of phytochemicals with in vitro and in vivo protective activities which deserves further mechanistic studies for its use as a hepatoprotective agent in the prevention of hepatic inflammation and its related malignancies.

Butea monosperma (Lam.) Taub. Bark fractions protect against free radicals and induce apoptosis in MCF-7 breast cancer cells via cell-cycle arrest and ROS-mediated pathway

Abstract Butea monosperma (Lam.) Taub. is an ethnomedicinal tree of remedial value in the treatment of diabetes, bone fractures, and liver and neurological disorders. However, the information available on DNA-protective and anti-proliferative potential of bark of this tree is scarce. In the present study, the extract/fractions obtained from bark of B. monosperma were evaluated for antioxidant, DNA-protective, and anti-proliferative activities, along with their phytochemical profiling for identifying major constituents present in them. Different extract/fractions, namely, Bmth (methanol), Bhex (hexane), Bchl (chloroform), and Beac (ethyl acetate), were prepared and evaluated for antioxidant activity using in vitro assays. Extract/fractions were also evaluated for anti-proliferative and apoptotic activity in human breast carcinoma cell line MCF-7, using in vitro assays, namely, MTT, clonogenic, and neutral comet assay, along with confocal microscopy and flow cytometry. Among all extract/fractions, a pronounced antioxidant activity was exhibited by Bchl and Beac fractions, in DPPH· (EC50 213.2 and 161.5 µg/mL, respectively), ABTS+· (EC50 139.3 and 44.1 µg/mL, respectively), and reducing power assay (EC50 86.7 and 84.5 µg/mL, respectively). Both fractions protected plasmid DNA against hydroxyl radical induced damage in plasmid nicking assay. Bchl and Beac were also observed to inhibit the growth of MCF-7 cells (GI50 203.7 and 246.5 µg/mL, respectively). Both fractions induced apoptosis in MCF-7 cells, by arresting the cell cycle in G1 and sub-G1 phase, respectively, enhancing ROS levels, decreasing mitochondrial membrane potential, and inducing double-strand DNA breaks. HPLC analysis revealed high kaempferol content in Bchl, and catechin, epicatechin, and gallic acid in Beac.

DNA Topoisomerase II: Promising Target for Anticancer Drugs

Topoisomerase II inhibitors are being researched as targets for the generation of antineoplastic drugs because inhibition of topoisomerase II by theses drugs leads to cell death. Inhibitors bind with topoisomerase molecule thus making the enzyme nonfunctional and converting it into a cellular toxin that fragments the genome. Cancer cells divide more rapidly than normal cells. Thus, cancer cells would be killed preferably instead of normal cells by topoisomerase inhibitors. The inhibitors which decrease the overall activity of this enzyme are called catalytic inhibitors and that increase the level of topoisomerase–DNA-cleaved complexes are called poisons. Topoisomerase poisons are further divided into intercalating and non-intercalating. Phytochemicals have proven to be rich sources of topoisomerase II inhibitors and widely used as anticancer drugs, whereas some are components of human diet and known to act as chemopreventive agents. The present review explains the role of both categories of topoisomerase II inhibitors, viz., catalytic inhibitors and poisons, and their role in cancer chemoprevention.