Jayaraj Ravindran

Bio: Jayaraj Ravindran is an academic researcher from University of Texas MD Anderson Cancer Center. The author has contributed to research in topics: Apoptosis & Downregulation and upregulation. The author has an hindex of 14, co-authored 19 publications receiving 2037 citations.

Curcumin and cancer cells: how many ways can curry kill tumor cells selectively?

Abstract: Cancer is a hyperproliferative disorder that is usually treated by chemotherapeutic agents that are toxic not only to tumor cells but also to normal cells, so these agents produce major side effects. In addition, these agents are highly expensive and thus not affordable for most. Moreover, such agents cannot be used for cancer prevention. Traditional medicines are generally free of the deleterious side effects and usually inexpensive. Curcumin, a component of turmeric (Curcuma longa), is one such agent that is safe, affordable, and efficacious. How curcumin kills tumor cells is the focus of this review. We show that curcumin modulates growth of tumor cells through regulation of multiple cell signaling pathways including cell proliferation pathway (cyclin D1, c-myc), cell survival pathway (Bcl-2, Bcl-xL, cFLIP, XIAP, c-IAP1), caspase activation pathway (caspase-8, 3, 9), tumor suppressor pathway (p53, p21) death receptor pathway (DR4, DR5), mitochondrial pathways, and protein kinase pathway (JNK, Akt, and AMPK). How curcumin selectively kills tumor cells, and not normal cells, is also described in detail.

NF-κB and cancer: how intimate is this relationship

Abstract: NF-κB, a transcription factor first discovered in 1986, is now known to be closely connected to the process of tumorogenesis based on a multiplicity of evidence. (1) NF-κB is activated in response to tobacco, stress, dietary agents, obesity, alcohol, infectious agents, irradiation, and environmental stimuli that account for as much as 95% of all cancers. (2) The transcription factor has been linked with transformation of cells. (3) It is constitutively active in most tumor cells. (4) It has also been linked with the survival of cancer stem cells, an early progenitor cell that has acquired self-renewal potential. (5) NF-κB regulates the expression of most anti-apoptotic gene products associated with the survival of the tumor. (6) It also regulates the gene products linked with proliferation of tumors. (7) The transcription factor controls the expression of gene products linked with invasion, angiogenesis, and metastasis of cancer. (8) While most carcinogens activate NF-κB, most chemopreventive agents suppress its activation. These observations suggest that NF-κB is intimately intertwined with cancer growth and metastasis. The mechanism that leads to constitutive activation of NF-κB in hematological, gastrointestinal, genitourinary, gynecological, thoracic head and neck, breast, and skin cancers, and the ways NF-κB is activated are the topics of discussion in this review.

γ-Tocotrienol Inhibits Pancreatic Tumors and Sensitizes Them to Gemcitabine Treatment by Modulating the Inflammatory Microenvironment

Abstract: Pancreatic cancers generally respond poorly to chemotherapy, prompting a need to identify agents that could sensitize tumors to treatment. In this study, we investigated the response of human pancreatic cells to γ-tocotrienol (γ-T3), a novel, unsaturated form of vitamin E found in palm oil and rice bran oil, to determine whether it could potentiate the effects of gemcitabine, a standard of care in clinical treatment of pancreatic cancer. γ-T3 inhibited the in vitro proliferation of pancreatic cancer cell lines with variable p53 status and potentiated gemcitabine-induced apoptosis. These effects correlated with an inhibition of NF-κB activation by γ-T3 and a suppression of key cellular regulators including cyclin D1, c-Myc, cyclooxygenase-2 (COX-2), Bcl-2, cellular inhibitor of apoptosis protein, survivin, vascular endothelial growth factor (VEGF), ICAM-1, and CXCR4. In an orthotopic nude mouse model of human pancreatic cancer, p.o. administration of γ-T3 inhibited tumor growth and enhanced the antitumor properties of gemcitabine. Immunohistochemical analysis indicated a correlation between tumor growth inhibition and reduced expression of Ki-67, COX-2, matrix metalloproteinase-9 (MMP-9), NF-κB p65, and VEGF in the tissue. Combination treatment also downregulated NF-κB activity along with the NF-κB-regulated gene products, such as cyclin D1, c-Myc, VEGF, MMP-9, and CXCR4. Consistent with an enhancement of tumor apoptosis, caspase activation was observed in tumor tissues. Overall, our findings suggest that γ-T3 can inhibit the growth of human pancreatic tumors and sensitize them to gemcitabine by suppressing NF-κB-mediated inflammatory pathways linked to tumorigenesis.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

Bright Side of Lignin Depolymerization: Toward New Platform Chemicals

Abstract: Lignin, a major component of lignocellulose, is the largest source of aromatic building blocks on the planet and harbors great potential to serve as starting material for the production of biobased products. Despite the initial challenges associated with the robust and irregular structure of lignin, the valorization of this intriguing aromatic biopolymer has come a long way: recently, many creative strategies emerged that deliver defined products via catalytic or biocatalytic depolymerization in good yields. The purpose of this review is to provide insight into these novel approaches and the potential application of such emerging new structures for the synthesis of biobased polymers or pharmacologically active molecules. Existing strategies for functionalization or defunctionalization of lignin-based compounds are also summarized. Following the whole value chain from raw lignocellulose through depolymerization to application whenever possible, specific lignin-based compounds emerge that could be in the fu...

Selective killing of cancer cells by a small molecule targeting the stress response to ROS

Abstract: A chemical screen has identified a small molecule, piperlongumine (PL), as a compound that induces selective killing of cancer cells. Piperlongumine acts by increasing reactive oxygen species (ROS) levels in cancer cells. Although it is active against a number of tumour models in vivo irrespective of p53 status, it does not affect normal tissues, including rapidly proliferating non-tumour cells. This work suggests a novel strategy for eradicating cancer cells by targeting the ROS stress-response pathway, but further work will be needed to identify determinants of piperlongumine sensitivity in a wider range of cancers. Malignant transformation, driven by gain-of-function mutations in oncogenes and loss-of-function mutations in tumour suppressor genes, results in cell deregulation that is frequently associated with enhanced cellular stress (for example, oxidative, replicative, metabolic and proteotoxic stress, and DNA damage)1. Adaptation to this stress phenotype is required for cancer cells to survive, and consequently cancer cells may become dependent upon non-oncogenes that do not ordinarily perform such a vital function in normal cells. Thus, targeting these non-oncogene dependencies in the context of a transformed genotype may result in a synthetic lethal interaction and the selective death of cancer cells2. Here we used a cell-based small-molecule screening and quantitative proteomics approach that resulted in the unbiased identification of a small molecule that selectively kills cancer cells but not normal cells. Piperlongumine increases the level of reactive oxygen species (ROS) and apoptotic cell death in both cancer cells and normal cells engineered to have a cancer genotype, irrespective of p53 status, but it has little effect on either rapidly or slowly dividing primary normal cells. Significant antitumour effects are observed in piperlongumine-treated mouse xenograft tumour models, with no apparent toxicity in normal mice. Moreover, piperlongumine potently inhibits the growth of spontaneously formed malignant breast tumours and their associated metastases in mice. Our results demonstrate the ability of a small molecule to induce apoptosis selectively in cells that have a cancer genotype, by targeting a non-oncogene co-dependency acquired through the expression of the cancer genotype in response to transformation-induced oxidative stress3,4,5.