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Kashef, Kimia,Radhakrishnan, Rangasudhagar,Lee, Clement M.,Reddy, E. Premkumar,Dhanasekaran, Danny N. Elsevier 2011 Neoplasia Vol.13 No.4
<P>The activated mutants of the 관-subunits of G proteins G(12) and G(13) have been designated as the gep oncogenes owing to their ability to stimulate diverse oncogenic signaling pathways that lead to neoplastic transformation of fibroblast cell lines and tumorigenesis in nude mice models. Studies from our laboratory as well as others have shown that the growth-promoting activities of G관(12) and G관(13) involve potent activation of c-Jun N-terminal kinases (JNKs). Our previous studies have indicated that the JNK-interacting leucine zipper protein (JLP), a scaffold protein involved in the structural and functional organization of the JNK/p38 mitogen-activated protein kinase module, tethers G관(12) and G관(13) to the JNK signaling module. In the present study, in addition to demonstrating the physical association between JLP and G관(12), we show that this interaction is enhanced by the receptor- or mutation-mediated activation of G관(12). We also establish that JLP interacts with G관(12) through the C-terminal domain that has been previously identified to be involved in binding to G관(13). Furthermore, using this C-terminal domain as a competitively inhibitor of JLP that can disrupt G관(12)-JLP interaction, we demonstrate that JLP is required for the stimulation of JNK by G관(12). Our results also indicate that such JLP interaction is required for G관(12) as well as G관(13)-mediated neoplastic transformation of JLP. These studies demonstrate for the first time a functional role for JLP in the gep oncogene-regulated neoplastic signaling pathway.</P>
Chemopreventive and Anticancer Effects of Thymoquinone: Cellular and Molecular Targets
Rohini Gomathinayagam,Ji Hee Ha,Muralidharan Jayaraman,송용상,Ciro Isidoro,Danny N. Dhanasekaran 대한암예방학회 2020 Journal of cancer prevention Vol.25 No.3
Thymoquinone (TQ) is a bioactive component derived from the seeds of Nigella sativa that are commonly as black cumin. Evidences indicate that the medicinal properties of TQ have been recognized for more than 2000 years. TQ has been shown to possess potent chemopreventive properties that include anti-inflammatory and anti-neoplastic activities. Recent studies have unraveled the multiple mechanisms through which TQ exerts its chemopreventive and anticancer activity in different cancer cells in a contextual manner. The present review aims to provide a brief compendium on the molecular mechanisms through which TQ inhibits signaling pathways underlying cancer genesis, progression, and metastasis.
Calorie Restriction for Cancer Prevention and Therapy: Mechanisms, Expectations, and Efficacy
Chiara Vidoni,Alessandra Ferraresi,Andrea Esposito,Chinmay Maheshwari,Danny N. Dhanasekaran,Vincenzo Mollace,Ciro Isidoro 대한암예방학회 2021 Journal of cancer prevention Vol.26 No.4
Cancer is one of the most frequently diagnosed diseases, and despite the continuous efforts in searching for new and more effective treatments, its morbidity and mortality remain a significant health problem worldwide. Calorie restriction, a dietary manipulation that consists in a reduction of the calorie intake, is gaining attention as a potential adjuvant intervention for preventing and/ or fighting cancer. Several forms of energy reduction intake, which includes caloric restriction tout-court, dietary restrictions, and intermittent fasting, are being explored for their ability to prevent or slow down cancer progression. Additionally, another anti-cancer approach being under investigation relies on the use of nutraceuticals known as “Caloric Restriction Mimetics” that can provide caloric restriction-mediated benefits without subjecting the patients to a strict diet. Preclinical in vitro and in vivo studies consistently show that diet modifiers reducing the calorie have impact on tumor microenvironment and cancer metabolism, resulting in reduced growth and progression of cancer. Preliminary clinical studies show that patients subjected to a reduced nutrient/energy intake experience improved outcomes from chemo- and radiotherapy while better tolerating the side effects. Here, we review the state of the art on the therapeutic potential of calorie restriction and of caloric restriction mimetics in preventing or retarding tumor development by modulating a subset of cellular processes. The most recent clinical progresses with caloric restriction mimetics in the clinical practice are also discussed.