Papers by Anupam Bishayee
Journal of Carcinogenesis & Mutagenesis, 2010
Silymarin and hepatocellular carcinoma
Anti-Cancer Drugs, 2015
The blessed milk thistle (Silybum marianum L.), a flowering plant native to Mediterranean Europe,... more The blessed milk thistle (Silybum marianum L.), a flowering plant native to Mediterranean Europe, has been consumed and extensively used as a cure for various chronic liver ailments over several centuries. Milk thistle extract, known as silymarin, is a complex mixture of seven major flavonolignans and one flavonoid. The phytoconstituents of silymarin owe their therapeutic and hepatoprotective effects to their strong antioxidant and anti-inflammatory properties. Primary liver cancer, also known as hepatocellular carcinoma (HCC), occurs in a milieu of oxidative stress and inflammation. The etiology of HCC includes chronic infection with hepatitis B and C viruses, cirrhosis, and exposure to dietary and environmental hepatocarcinogens. Current therapeutic options for HCC, including surgical resection and liver transplantation, have limited benefits and are essentially ineffective. Chemoprevention, using phytochemicals with potent antioxidant and anti-inflammatory properties, represents a fascinating strategy, which has been a subject of intense investigation in the recent years. In this review, we explore the potential role of silymarin as a chemopreventive and therapeutic agent for HCC. The review systematically evaluates the preclinical in-vitro and in-vivo studies investigating the effects of silymarin and its constituents on HCC. The biochemical mechanisms involved in the anti-liver-cancer effects of silymarin have been presented. The current status of clinical studies evaluating the potential of role of silymarin in liver cancer, especially that caused by hepatitis C virus, has also been examined. Potential challenges and future directions of research involved in the 'bench-to-bedside' transition of silymarin phytoconstituents for the chemoprevention and treatment of HCC have also been discussed.
Assessing health conditions and medication use among the homeless community in Long Beach, California
Journal of Research in Pharmacy Practice, 2014
Persons experiencing homelessness are a vulnerable population and are at increased risk for morbi... more Persons experiencing homelessness are a vulnerable population and are at increased risk for morbidity and all-cause mortality compared to the general population. This study sought to evaluate medication use, regular physician visits, and identify health conditions among the homeless population of Long Beach, California. Two "brown bag" medication review events were held at homeless shelters in the Long Beach area. Demographic information, medication use, and comorbid disease states were obtained through surveys. Three-fourths of the cohort (95 participants) consisted of males, and the average age of participants was 48 years. Psychiatric disorders and cardiovascular disease were the most common disease states reported at 32% and 46%, respectively and so were medications used in treating these chronic diseases. Medication adherence was found to be a significant problem in this population, where more than 30% of patients were nonadherent to medications for chronic diseases. Furthermore, foot problems, hearing and vision difficulties constitute the most commonly overlooked health problems within the homeless population. Based on this and other similar finding, we must accept that the homeless represent a vulnerable population, and that because of this fact, more programs should be focused at improving availability and access to health care among the homeless. Regarding the high number of reported health problems in the study, more studies are needed and more studies should incorporate screening for foot, hearing, and vision issues, both to increase awareness and to provide an opportunity for devising possible solutions to these highly preventable conditions.
Breast Cancer Prevention with a Novel Oleanane Triterpenoid: Preclinical Evidence and Anti-inflammatory Mechanisms
Planta Medica, 2013
International Journal of Molecular Sciences, 2015
Trianthema portulacastrum, a medicinal and dietary plant, has gained substantial importance due t... more Trianthema portulacastrum, a medicinal and dietary plant, has gained substantial importance due to its various pharmacological properties, including anti-inflammatory and anticarcinogenic activities. We have recently reported that a characterized T. portulacastrum extract (TPE) affords a considerable chemoprevention of 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary tumorigenesis though the underlying mechanisms are not completely understood. The objective of this study was to investigate anti-inflammatory mechanisms of TPE during DMBA mammary carcinogenesis in rats by monitoring cyclooxygenase-2 (COX-2), heat shock protein 90 (HSP90), nuclear factor-kappaB (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2). Mammary tumors were harvested from our previous study in which TPE (50-200 mg/kg) was found to inhibit mammary tumorigenesis in a dose-response manner. The expressions of intratumor COX-2, HSP90, NF-κB, inhibitory kappaB-alpha (IκBα) and Nrf2 were determined by immunohistochemistry. TPE downregulated the expression of COX-2 and HSP90, blocked the degradation of IκBα, hampered the translocation of NF-κB from cytosol to nucleus and upregulated the expression and nuclear translocation of Nrf2 during DMBA mammary carcinogenesis. These results in conjunction with our previous findings suggest that TPE prevents OPEN ACCESS DMBA-induced breast neoplasia by anti-inflammatory mechanisms mediated through simultaneous and differential modulation of two interconnected molecular circuits, namely NF-κB and Nrf2 signaling pathways.
Biological Trace Element Research, 1995
The influence of vanadium, an important dietary micronutrient, was evaluated on the cytosolic red... more The influence of vanadium, an important dietary micronutrient, was evaluated on the cytosolic reduced glutathione (GSH) content and glutathione S-transferase (GST) activity in several rat target tissues. Supplementation of drinking water with vanadium at the level of 0.2 or 0.5 ppm for 4, 8, or 12 wk was found to increase the GSH level with a concomitant elevation in GST activity in the liver followed by small intestine mucosa, large intestine mucosa, and kidney. The results were almost dose-dependent and mostly pronounced with 0.5 ppm vanadium after 12 wk of its continuous supplementation. Neither the GSH level nor GST activity was significantly altered in forestomach and lung following vanadium supplementation throughout the study. The levels of vanadium that were found to increase the content of GSH and activity of GST in the liver, intestine, and kidney did not exert any toxic manifestation as evidenced from water and food consumption as well as the growth responses of the experimental animals. Moreover, these doses of vanadium did not impair either hepatic or renal functions as they did not alter the serum activities of glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), sorbitol dehydrogenase (SDH), as well as serum urea and creatinine level. All these results clearly indicate that vanadium under the doses employed in our study has a significant inducing role on GSH content with a concurrent elevation in GST activity in the liver and specific extrahepatic tissues without any apparent sign of cytotoxicity. This attribute of vanadium may have a greater importance in terms of biotransformation and detoxification of xenobiotics, 276 Bishayee and Chatterjee including carcinogens. In addition, since the ability to afford an increment in the endogenous GSH-GST pool by anticarcinogenic natural substances has been found to correlate with their activity to inhibit neoplastic transformation, the trace element vanadium may be considered as a novel anticancer agent.
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 2014
Please cite this article in press as: A. Bishayee, A. Mandal, Trianthema portulacastrum Linn. exe... more Please cite this article in press as: A. Bishayee, A. Mandal, Trianthema portulacastrum Linn. exerts chemoprevention of 7,12-dimethylbenz(a)anthracene-induced mammary tumorigenesis in rats, Mutat. Res.: Fundam. Mol. Mech. Mutagen. (2014), http://dx.
Pomegranate-Derived Constituents as Inducers of Cell Death: Implications in Cancer Prevention and Therapy
Natural compounds as inducers of cell death, 2012
Suppression of inflammatory cascade is implicated in methyl amooranin-mediated inhibition of experimental mammary carcinogenesis
Molecular Carcinogenesis, 2013
Breast cancer represents the second leading cause of cancer-related deaths among women worldwide ... more Breast cancer represents the second leading cause of cancer-related deaths among women worldwide and preventive therapy could reverse or delay the devastating impact of this disease. Methyl-amooranin (methyl-25-hydroxy-3-oxoolean-12-en-28-oate, AMR-Me), a novel synthetic oleanane triterpenoid, reduced the incidence and burden of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumors in rats through antiproliferative and proapoptotic effects. Since chronic inflammation plays an important role in the pathogenesis of breast cancer and several synthetic oleanane compounds are known potent anti-inflammatory agents, we aim to investigate anti-inflammatory mechanisms of AMR-Me by monitoring various proinflammatory and stress markers, such as cyclooxygenase-2 (COX-2) and heat shock protein 90 (HSP90), and nuclear factor-κB (NF-κB) signaling during DMBA mammary tumorigenesis in rats. Mammary tumors were harvested from a chemopreventive study in which AMR-Me (0.8-1.6 mg/kg) was found to inhibit mammary carcinogenesis in a dose-response manner. The expressions of COX-2, HSP90, NF-κB, and inhibitory κB-α (IκB-α) were determined by immunohistochemistry and reverse transcription-polymerase chain reaction. AMR-Me downregulated the expression of intratumor COX-2 and HSP90, suppressed the degradation of IκB-α, and reduced the translocation of NF-κB from cytosol to nucleus. Our present study provides the first in vivo evidence that NF-κB-evoked inflammatory cascade is a major target of AMR-Me in breast cancer. Our current results together with our previous findings suggest that disruption of NF-κB signaling contributes to anti-inflammatory, antiproliferative, and apoptosis-inducing mechanisms involved in AMR-Me-mediated chemoprevention of rat mammary carcinogenesis. These encouraging mechanistic results coupled with a safety profile should facilitate the clinical development of AMR-Me as breast cancer chemopreventive drug.
Oleanane triterpenoids in the prevention and therapy of breast cancer: current evidence and future perspectives
Phytochemistry Reviews, 2014
Breast cancer is one of the most frequently diagnosed cancers and major cause of death in women i... more Breast cancer is one of the most frequently diagnosed cancers and major cause of death in women in the world. Emerging evidence underscores the value of dietary and non-dietary phytochemicals, including triterpenoids, in the prevention and treatment of breast cancer. Oleanolic acid, an oleanane-type pentacyclic triterpenoid, is present in a large number of dietary and medicinal plants. Oleanolic acid and its derivatives exhibit several promising pharmacological activities, including antioxidant, anti-inflammatory, hepatoprotective, cardioprotective, antipruritic, spasmolytic, antiallergic, antimicrobial and antiviral effects. Numerous studies indicate that oleanolic acid and other oleanane triterpenoids modulate multiple intracellular signaling pathways and exert chemopreventive and antitumor activities in various in vitro and in vivo model systems. A series of novel synthetic oleanane triterpenoids have been prepared by chemical modifications of oleanolic acid and some of these compounds are considered to be the most potent anti-inflammatory and anticarcinogenic triterpenoids. Accumulating studies provide extensive evidence that synthetic oleanane derivatives inhibit proliferation and induce apoptosis of various cancer cells in vitro and demonstrate cancer preventive or antitumor efficacy in animal models of blood, breast, colon, connective tissue, liver, lung, pancreas, prostate and skin cancer. This review critically examines the potential role of oleanolic acid, oleanane triterpenoids and related synthetic compounds in the chemoprevention and treatment of mammary neoplasia. Both in vitro and in vivo studies on these agents and related molecular mechanisms are presented. Several challenges and future directions of research to translate already available impressive preclinical knowledge to clinical practice of breast cancer prevention and therapy are also presented.
Modulation of the Nrf2 Signaling Pathway by Chemopreventive Dietary Phytoconstituents
Nutrition, Diet and Cancer, 2012
Effects of Human Placental Extract on Brain Monoamines and Monoamine Oxidase Activity in Rats
The Tohoku Journal of Experimental Medicine, 1995
Human placental extract, an agent clinically used world-wide in a number of physiological anomali... more Human placental extract, an agent clinically used world-wide in a number of physiological anomalies, has been claimed to be effective in children of slow learners. Since the monoaminergic neurotransmitter systems in the brain play an important role in the processes of learning and memory, we examined the effects of human placental extract on the levels of norepinephrine, dopamine and serotonine in rat brain as an attempt to evaluate the possible underlying biochemical mechanism of action of the extract. We also determined the changes of brain monoamine oxidase (MAO) activity following placental extract treatment. The results showed that subchronic (5, 10, 15 or 20) administration of placental extract (2-4 ml/kg/day) had the effect of increasing all the monoamines and decreasing the MAO activity which could be the possible mode of action of the extract in slow learners.
1α, 25-Dihydroxyvitamin D3 inhibits hepatic chromosomal aberrations, DNA strand breaks and specific DNA adducts during rat hepatocarcinogenesis
Experientia, 2001
The possible promoting effect of streptozotocin (STZ; 65 mg/kg body weight, intraperitoneal)-indu... more The possible promoting effect of streptozotocin (STZ; 65 mg/kg body weight, intraperitoneal)-induced diabetes during 2-acetylaminofluorene (2-AAF; 0.04% in basal diet)-initiated hepatocarcinogenesis and modulatory effect of 1α,25-dihydroxyvitamin D3 (VD3; 0.3 μg/0.1 ml in propylene glycol, per os) were investigated by monitoring chromosomal aberrations (CAs), DNA strand breaks and specific DNA adducts in rat liver. VD3 treatment (twice a week) was started 4 weeks before the 2-AAF regimen and continued throughout the study. Aberrant metaphase chromosomes were counted from the regenerating hepatocytes 15, 30 or 45 weeks after STZ injection, while DNA strand break and adduct assays were performed 45 days post-STZ treatment. Dietary exposure to 2-AAF elicited a substantial increase in CAs and elevated the extent of DNA strand breaks and formation of N-(deoxyguanosin-8-yl)-2-aminofluorene. A promoting effect of STZ was evident from CAs coupled with DNA strand break analysis. VD3 treatment substantially reducted 2-AAF+STZ-induced CAs as well as DNA strand breaks and adducts. Thus, VD3 appears to be effective in suppressing liver-specific early chromosomal as well as DNA damage during the process of rat hepatocarcinogenesis initiated with 2-AAF and promoted by STZ contributing to its promise as a cancer chemotherapeutic agent.
Radioprotection against Lethal Damage Caused by Chronic Irradiation with Radionuclides In Vitro
Radiation Research, 1998
To examine the capacity of chemical protectors to mitigate damage caused by chronic irradiation b... more To examine the capacity of chemical protectors to mitigate damage caused by chronic irradiation by incorporated radionuclides in vitro, cells must be maintained in the presence of the protector during the course of the irradiation. Such long exposures to chemical protectors at concentrations high enough to afford protection usually results in extreme chemotoxicity. To overcome this problem, experimental conditions were developed to allow Chinese hamster V79 cells to be maintained in 5% DMSO for prolonged periods (up to 72 h) with no observable chemotoxicity. Under these conditions, the capacity of DMSO to protect against damage to V79 cells caused by unbound 32P and 3H2O and DNA-incorporated (131)IdU, [3H]dThd and 125IdU was examined. The dose modification factors for 32P, 3H2O, (131)IdU, [3H]dThd and 125IdU were 2.6+/-0.5, 2.3+/-0.3, 1.0+/-0.1, 1.16+/-0.07 and 1.07+/-0.02, respectively. These results show that 5% DMSO is capable of protecting cultured V79 cells against lethal damage caused by beta particles emitted by unbound 32P and 3H2O, whereas little or no protection is afforded against damage caused by beta particles emitted by DNA-incorporated (131)I and 3H or low-energy Auger electrons emitted by DNA-incorporated 125I.
Cancer Preventive and Curative Attributes of Plants of the Cactaceae Family: A Review
Planta Medica, 2013
The ever-increasing occurrence of cancer and the severe side effects and limited efficacy of curr... more The ever-increasing occurrence of cancer and the severe side effects and limited efficacy of current cancer chemotherapy based on chemical drugs shift the attention toward drugs of plant origin. The Cactaceae family comprises more than 1500 species, but until recently only a few of them have been tested for their chemopreventive and anticancer attributes, leaving a wide unexplored area still waiting for researchers to investigate. Considering this fact, and also the promising results obtained with the relatively few plants of this family already tested, it should justly be expected that some plants of the Cactaceae family yet unexplored might possess outstanding anticancer attributes, exceeding those displayed by the plants already tested. This review presents in vitro and in vivo experimental evidence on cancer chemopreventive and therapeutic potential of bioactive phytoconstituents and extracts derived from cactus plants. It also examines the underlying biochemical and molecular mechanisms involved in the antineoplastic effects of plants of the Cactaceae family. Current limitation and future directions of research towards effective use of cacti to develop efficient and side effect-free future cancer-preventive and anticancer drugs are also discussed.
Protective Effects of Mikania cordata Root Extract Against Physical and Chemical Factors-Induced Gastric Erosions in Experimental Animals
Planta Medica, 1994
The effect of the methanolic fraction of Mikania cordata (Burm., B. L. Robinson) root extract was... more The effect of the methanolic fraction of Mikania cordata (Burm., B. L. Robinson) root extract was investigated for its possible ulceroprotective activity in male Sprague-Dawley rats. Oral administration of this extract (50, 100, or 150 mg/kg) significantly prevented the occurrence of water immersion stress-induced gastric ulcers in a dose-responsive manner. The extract also dose-dependently inhibited gastric ulcers induced by ethanol, aspirin, and phenylbutazone. The ED50 values of the extract in the above four ulcer models were found to be 95.1, 109.7, 125.5, and 136.2 mg/kg, respectively. The volume, acidity, and peptic activity of the gastric juice in pylorous-ligated rats were not altered upon administration of the extract (100 or 150 mg/kg) but it significantly and dose-dependently promoted the gastric mucus secretion in normal as well as stress- and ethanol-induced ulcerated animals. Based on these results, we conclude that M. cordata root extract possesses antiulcer activity and that the observed activity may be due to the modulation of defensive factors through an improvement of gastric cytoprotection.
Cancer Preventive and Curative Attributes of Plants of the Cactaceae Family: A Review
Planta Medica, 2013
The ever-increasing occurrence of cancer and the severe side effects and limited efficacy of curr... more The ever-increasing occurrence of cancer and the severe side effects and limited efficacy of current cancer chemotherapy based on chemical drugs shift the attention toward drugs of plant origin. The Cactaceae family comprises more than 1500 species, but until recently only a few of them have been tested for their chemopreventive and anticancer attributes, leaving a wide unexplored area still waiting for researchers to investigate. Considering this fact, and also the promising results obtained with the relatively few plants of this family already tested, it should justly be expected that some plants of the Cactaceae family yet unexplored might possess outstanding anticancer attributes, exceeding those displayed by the plants already tested. This review presents in vitro and in vivo experimental evidence on cancer chemopreventive and therapeutic potential of bioactive phytoconstituents and extracts derived from cactus plants. It also examines the underlying biochemical and molecular mechanisms involved in the antineoplastic effects of plants of the Cactaceae family. Current limitation and future directions of research towards effective use of cacti to develop efficient and side effect-free future cancer-preventive and anticancer drugs are also discussed.
Anticancer Potential of Aloes: Antioxidant, Antiproliferative, and Immunostimulatory Attributes
Planta Medica, 2012
Aloe is a genus of medicinal plants with a notable history of medical use. Basic research over th... more Aloe is a genus of medicinal plants with a notable history of medical use. Basic research over the past couple of decades has begun to reveal the extent of Aloe's pharmaceutical potential, particularly against neoplastic disease. This review looks at Aloe, both the genus and the folk medicine, often being called informally "aloes", and delineates their chemistry and anticancer pharmacognosy. Structures of key compounds are provided, and their pharmacological activities reviewed. Particular attention is given to their free radical scavenging, antiproliferative, and immunostimulatory properties. This review highlights major research directions on aloes, reflecting the enormous potential of natural sources, and of the genus Aloe in particular, in preventing and treating cancer.
Phytotherapy Research, 1994
Cymnema syluestre R. Br. leaf extract (25-100 mgkg) when orally administered to experimentally in... more Cymnema syluestre R. Br. leaf extract (25-100 mgkg) when orally administered to experimentally induced hyperlipidaemic rats for 2 weeks, reduced the elevated serum triglyceride (TG), total cholesterol (TC), very lowdensity lipoprotein (VLDL)-and low-density lipoprotein (LDL)-cholesterol in a dose-dependent manner. The decreased serum high-density lipoprotein (HDL)-cholesterol and antiatherogenic index (AAI) in hyperlipidaemia were also reversed towards normalization. The ability of this extract (at 100 mg/kg) to lower TG and TC in Serum and its antiatherosclerotic potential were almost similar to that of a standard lipid lowering agent-clofibrate.
Phytotherapy Research, 1997
The efficacy of an ethanol extract of Trianthema portulacastrum as a hepatoprotective agent was i... more The efficacy of an ethanol extract of Trianthema portulacastrum as a hepatoprotective agent was investigated against carbon tetrachloride (CCl 4 )-induced chronic liver injury in mice. The CCl 4 was administered per os (p.o.) three times a week for 5 weeks. Daily administration (p.o.) of T. portulacastrum plant extract at 100 or 150 mg/kg was started 2 weeks before the commencement of CCl 4 treatment and it continued during the entire period of the treatment. The extract dose-dependently decreased the activities of serum glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, lactate dehydrogenase, alkaline phosphatase, glutamate dehydrogenase and sorbitol dehydrogenase as well as serum levels of bilirubin and urea which were otherwise significantly elevated with the chronic CCl 4 regimen alone. There was a substantial increase in the activities of plasma membrane enzymes ␥-glutamyl transpeptidase and 5Ј-nucleotidase and lysosomal enzymes acid phosphatase and acid ribonuclease in hepatic tissue following CCl 4 treatment. These changes were reversed towards normalization with the extract in a dose-dependent manner. The extract also restored CCl 4 -induced inhibition of hepatic microsomal enzyme glucose-6-phosphatase. The activities of mitochondrial succinate dehydrogenase and adenosine 5Ј-triphosphatase which were significantly attenuated by CCl 4 administration remained unaltered following the extract therapy. Results of this study provide evidence that the extract possesses a marked liver protective action which is comparable to that of silymarin, a standard hepatoprotective drug. The probable mechanism by which this plant exerts cytoprotection has also been discussed.
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Papers by Anupam Bishayee