Bharat Aggarwal

Bharat Aggarwal
University of Texas MD Anderson Cancer Center | MD Anderson · Department of Experimental Therapeutics

About

737
Publications
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127,574
Citations

Publications

Publications (737)
Chapter
It has been established that chronic inflammation plays a critical role in chronic diseases including cancers. Inflammation regulates various steps of neoplasia and is crucial in the tumor microenvironment. In the tumor microenvironment, proinflammatory gene products mediate various undesirable pathological processes including apoptosis suppression...
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Background: Tumor microenvironment (TME) has a pivotal impact on tumor progression, and epithelial-mesenchymal transition (EMT) is an extremely crucial initial event in the metastatic process in colorectal cancer (CRC) that is not yet fully understood. Calebin A (an ingredient in Curcuma longa ) has been shown to repress CRC tumor growth. However,...
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Background Cytokine storm is the exaggerated immune response often observed in viral infections. It is also intimately linked with the progression of COVID-19 disease as well as associated complications and mortality. Therefore, targeting the cytokine storm might help in reducing COVID-19-associated health complications. The number of COVID-associa...
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It has been established that inflammation plays an important role in bone formation and bone loss. Although a lot is known about the role of TNF-α in bone health, very little is understood about TNF-β, also called lymphotoxin. In this report, we examine the effect of TNF-β on osteogenic differentiation of mesenchymal stem cells (MSCs) and its modul...
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Objective: The majority of chemotherapeutic agents stimulate NF-κB signaling that mediates cell survival, proliferation and metastasis. The natural turmeric non-curcuminoid derivate Calebin A has been shown to suppress cell growth, invasion and colony formation in colorectal cancer cells (CRC) by suppression of NF-κB signaling. Therefore, we hypot...
Article
Most chronic diseases, caused by lifestyle factors, appear to be linked to inflammation. Inflammation is activated mechanistically, and nuclear factor-κB (NF-κB) is a significant mediator. NF-κB, one of the most studied transcription factors, was first identified in the nucleus of B lymphocytes almost three decades ago. This protein has a key funct...
Article
Introduction: Since ancient times, turmeric has been used in several folklore remedies against various ailments. The principle component of turmeric is curcumin and its efficacy has been advocated in in vitro, in vivo and clinical studies for different chronic diseases. However, some studies suggest that curcumin bioavailability is a major problem....
Article
Impact statement: The success rate for cancer drugs which enter into phase 1 clinical trials is utterly less. Why the vast majority of drugs fail is not understood but suggests that pre-clinical studies are not adequate for human diseases. In 1975, as per the Tufts Center for the Study of Drug Development, pharmaceutical industries expended 100 mi...
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Objective: Tumor necrosis factor-beta (TNF-β), as an inflammatory mediator that has been shown to promote tumorigenesis, induces NF-κB. Natural multi-targeted agent resveratrol in turn shows anti-inflammatory and anti-cancer properties. Epithelial-to-mesenchymal transition (EMT) allows cancer cells to turn into a motile state with invasive capaciti...
Article
In the original version of this article (1), images of experimental controls in Figs. 2B, 2C, and 3A are the same as those in Figs. 4B, 4C, and 3A, respectively, in a previously published article (2). The authors explained that the experiments were intentionally designed so that the same controls could be used to test different experimental conditi...
Article
Impact statement: The mechanism by which natural products such as resveratrol suppresses TNF-β-promoted tumor cell proliferation, invasion, and colony formation is unknown. In this study, we explored for the first time the effect of resveratrol on the proinflammatory cytokine TNF-β-, compared to TNF-α-stimulated proliferative and pro-inflammatory...
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Increasing evidence from diverse sources during the past several years has indicated that long-term, low level, chronic inflammation mediates several chronic diseases including cancer, arthritis, obesity, diabetes, cardiovascular diseases, and neurological diseases. The inflammatory molecules and transcription factors, adhesion molecules, AP-1, che...
Article
Extensive research during last 2 decades has revealed that most drugs discovered today, although costs billions of dollars for discovery, and yet they are highly ineffective in their clinical response. For instance, the European Medicines Agency has approved 68 anti-cancer drugs, and out of which 39 has reached the market level with no indication o...
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Objective: Resveratrol, a safe and multitargeted natural agent, has been linked with inhibition of survival and invasion of tumor cells. Tumor Necrosis Factor-β (TNF-β) (Lymphotoxin α) is known as an inflammatory cytokine, however, the underlying mechanisms for its pro-carcinogenic effects and whether resveratrol can suppress these effects in the t...
Article
Bone loss or osteoporosis, is a slow-progressing disease that results from dysregulation of pro-inflammatory cytokines. The FDA has approved number of drugs for bone loss prevention, nonetheless all are expensive and have multiple side effects. The nutraceuticals identified from dietary agents such as butein, cardamonin, coronarin D curcumin, diosg...
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Extensive research within the last several decades has revealed that the major risk factors for most chronic diseases are infections, obesity, alcohol, tobacco, radiation, environmental pollutants, and diet. It is now well established that these factors induce chronic diseases through induction of inflammation. However, inflammation could be either...
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Extensive research within last two decades has indicated that curcumin extracted from turmeric (Curcuma longa), exhibits anticancer potential, in part through the modulation of inflammatory pathways. However, the residual antitumor activity of curcumin-free turmeric (CFT) relative to curcumin or turmeric is not well-understood. In the present study...
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While Lymphotoxin α (TNF-β), a product of lymphocytes, is known to play a pivotal role in inflammatory joint environment, resveratrol has been shown to possess anti-inflammatory and chondroprotective effects via activation of the histondeacetylase Sirt1. Whether TNF-β induction of inflammatory pathways in primary human chondrocytes (PCH) can be mod...
Article
Curcumin, a component of a spice native to India, was first isolated in 1815 by Vogel and Pelletier from the rhizomes of Curcuma longa (turmeric) and, subsequently, the chemical structure of curcumin as diferuloylmethane was reported by Milobedzka et al. [(1910) 43., 2163-2170].Since then, this polyphenol has been shown to exhibit antioxidant, anti...
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Although it is widely accepted that better food habits do play important role in cancer prevention and treatment, how dietary agents mediate their effects remains poorly understood. More than thousand different polyphenols have been identified from dietary plants. In this review, we discuss the underlying mechanism by which dietary agents can modul...
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Background: While the anti-inflammatory and anticancer potential of curcumin, which is derived from turmeric (Curcuma longa), has been studied extensively, very little is known about Calebin A, another novel compound from the same source. Purpose: To determine whether Calebin A exhibits anti-inflammatory and anticancer potential. Methods: We e...
Article
Background: For centuries, agents derived from natural sources (mother nature), especially plants have been the primary source of medicine. Neem, also referred to as Azadirachta indica is one such plant that has been so named because it provides freedom from all diseases, and used for thousands of years in Indian and African continents. Different...
Chapter
Curcumin is a polyphenol derived from the rhizomes of the turmeric (golden spice) that has been used in Ayurveda and traditional Chinese medicine since ancient times. Curcumin is a highly pleiotropic molecule; its safety and efficacy has been demonstrated in cell-based studies and in animal models. The pharmacokinetics, safety, and efficacy of curc...
Article
Curcumin, a yellow pigment in the Indian spice Turmeric (Curcuma longa), which is chemically known as diferuloylmethane, was first isolated exactly two centuries ago in 1815 by two German Scientists, Vogel and Pelletier. However, according to the pubmed database, the first study on its biological activity as an antibacterial agent was published in...
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Cancer is primarily an "old-age" disease that has an "age-old" history. The overall incidence of cancer is much higher in Western countries, but is rapidly growing in Eastern countries perhaps due to change in life-style. Almost three million studies published to date indicate that cancer is a hyperproliferative disorder that arises from dysregulat...
Article
Background: Colorectal cancer (CRC) is one of the most common malignancies worldwide and even develops resistance to chemotherapeutic agents over time. As a result survival for patients with CRC remains poor. Method: We investigated both in vitro and in vivo effects of γ-tocotrienol (γ-T3) alone and in combination with capecitabine. Apoptosis an...
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This article has been retracted by the publisher. Fig. 1B was assembled from a composite of many images. The actin immunoblot from Fig. 2A, right, was reused in Fig. 4A, left. Parts of the actin immunoblot from Fig. 2C, left panel, had been reused in supplemental Fig. 1A. The actin immunoblot from Figs. 2E and 4B, left panels; and supplemental Fig....
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This article has been retracted by the publisher. An investigation at MD Anderson determined that image of control HCT116 cells treated with TRAIL and the image of cells transfected with CHOP siRNA and treated with TRAIL in Fig. 5C were reused. Additionally, the Journal determined that the actin immunoblot in Fig. 2A was reused as the actin immunob...
Article
Novel drug development leading to final approval by the US FDA can cost as much as two billion dollars. Why the cost of novel drug discovery is so expensive is unclear, but high failure rates at the preclinical and clinical stages are major reasons. Although therapies targeting a given cell signaling pathway or a protein have become prominent in dr...
Article
Background: Tumor necrosis factor-α (TNF-α) is a key inflammatory mediator and its reduction is a therapeutic target in several inflammatory diseases. Curcumin, a bioactive polyphenol from turmeric, has been shown in several preclinical studies to block TNF-α effectively. However, clinical evidence has not been fully conclusive. Objective: The a...
Article
The development of chemoresistance in human pancreatic cancer is one reason for the poor survival rate for patients with this cancer. Because multiple gene products are linked with chemoresistance, we investigated the ability of ursolic acid (UA) to sensitize pancreatic cancer cells to gemcitabine, a standard drug used for the treatment of pancreat...
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Escaping from cell death is one of the adaptations that enable cancer cells to stave off anticancer therapies. The key players in avoiding apoptosis are collectively known as survival proteins. Survival proteins comprise the Bcl-2, inhibitor of apoptosis (IAP), and heat shock protein (HSP) families. The aberrant expression of these proteins is asso...
Article
Osteoporosis is a bone disease that is exacerbated by aging and age-associated chronic diseases such as cancer. Cancer-induced bone loss is usually treated with bisphosphonates or denosumab, an antibody against receptor activator of nuclear factor (NF)-κB ligand (RANKL). Because these drugs are expensive and have numerous side effects and high rate...
Book
This comprehensive volume focuses on anti-inflammatory nutraceuticals and their role in various chronic diseases. Food and Drug Administration (FDA) approved drugs such as steroids, non-steroidal anti-inflammatory drugs (NSAIDS), statins and metformin have been shown to modulate inflammatory pathways, but their long-term intake has been associated...
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Considering that as many as 80 % of the anticancer drugs have their roots in natural products derived from traditional medicine, we examined compounds other than curcumin from turmeric (Curcuma longa) that could exhibit anticancer potential. Present study describes the isolation and characterization of another turmeric-derived compound, β-sesquiphe...
Chapter
Cancer is primarily an “old-age disease” that has an “age-old” history. The overall incidence of cancer is much higher in Western countries than in Eastern countries for reasons that are not understood. Almost three million studies published to date indicate that cancer is a hyperproliferative disorder that arises from dysregulation of multiple cel...
Article
Oncogene is one of the world’s leading cancer journals. It is published weekly and covers all aspects of the structure and function of Oncogenes.
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Full-text available
Curcumin (diferuloylmethane), a golden pigment from turmeric, has been linked with antioxidant, anti-inflammatory, anticancer, antiviral, antibacterial, and antidiabetic properties. Most of the these activities have been assigned to methoxy, hydroxyl, α,β-unsaturated carbonyl moiety or to diketone groups present in curcumin. One of the major metabo...
Article
Whether it is chronic myeloid leukemia, ALK-expressing malignancies, or HER2-positive breast cancer, targeted-therapies for treatment of human cancers have shown great promise. However, as they hit a single molecule expressed in neoplastic cells, their use is frequently associated with development of resistance. In cancer cells many signaling pathw...
Article
Selective killing of cancer cells is one of the major goals of cancer therapy. Although chemotherapeutic agents are being used for cancer treatment, they lack selectivity toward tumor cells. Among the six different death receptors (DRs) identified to date, DR4 and DR5 are selectively expressed on cancer cells. Therefore, unlike chemotherapeutic age...
Article
Chronic infections, obesity, alcohol, tobacco, radiation, environmental pollutants, and high-calorie diet have been recognized as major risk factors for the most chronic diseases including cancer. All these risk factors are linked to chronic diseases through inflammation. While acute inflammation that persists for short-term mediates host defense a...
Article
Recently two different reports appeared in prominent journals suggesting a mechanism by which piperlonguimine, a pyridine alkaloid, mediates anticancer effects. In the current report, we describe another novel mechanism by which this alkaloid mediates its anticellular effects. We found that piperlonguimine blocked both constitutive and inducible NF...
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In a search of new compounds active against cancer, synthesis of a series of C-5 curcumin analogues was carried out. The new compounds demonstrated good cytotoxicity against chronic myeloid leukemia (KBM5) and colon cancer (HCT116) cell lines. Further, these compounds were found to have better potential to inhibit TNF- α -induced NF- κ B activation...
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A series of C5-curcumin bearing morpholine based dithiocarbamates was synthesized. Molinspiration and Osiris software were used for theoretical prediction of physico-chemical properties of these molecules and the majority of the hybrids showed theoretical physico-chemical properties similar or better than curcumin. These hybrids (4a-4v) were evalua...
Article
Human tumor necrosis factor (TNF), first isolated by our group as an anticancer agent, has been now shown to be a primary mediator of inflammation. Till today 19 different members of the TNF superfamily which interact with 29 different receptors, have been identified. Most members of this family exhibit pro-inflammatory activities, in part through...
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Full-text available
Curcumin (diferuloylmethane) is a yellow pigment present in the spice turmeric (Curcuma longa) that has been associated with antioxidant, anti-inflammatory, anticancer, antiviral, and antibacterial activities as indicated by over 6,000 citations. In addition, over one hundred clinical studies have been carried out with curcumin. One of the major pr...