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mitocans as Novel Agents for Anticancer Therapy: An Overview

International Journal of Clinical Medicine 2011年第4期2卷 515-529页

作者： Vandana Panda Prashant Khambat Sachin Patil 不详

Many conventional anticancer drugs have an associated lack of safety by their toxicity. Relatively faster mutations in tumor cells pose a significant obstacle in treatment of cancer. Recently, “mitocans” have emerged as a novel class of anticancer agents selectively targeting tumor cells and thus, are much less toxic than conventional anticancer chemotherapeutic agents. mitocans are drugs that act directly on mitochondria within the cell, thus causing changes in energy metabolism of the cell. Amongst these mitocans, α-Tocopheryl succinate or vitamin E analogs are studied very well by researchers. This review discusses mitochondrial drug targeting strategies and a variety of novel mitochondrial drug targets of mitocans, such as electron transport chain, mitochondrial permeability transition, Bcl-2 family proteins and mitochondrial DNA. The purpose of this review is to focus on the various classes of mitocans, the mechanisms by which these drugs specifically act on tumor cells and their applications in cancer chemotherapeutics.

关键词： mitocans Mitochondria Cancer Apoptosis Membrane Permeabilization Energy Metabolism

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NSAID celecoxib: a potent mitochondrial pro-oxidant cytotoxic agent sensitizing metastatic cancers and cancer stem cells to chemotherapy

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Journal of Cancer Metastasis and Treatment 2018年第1期4卷 571-596页

作者： Stephen John Ralph Sam Nozuhur Rafael Moreno-Sanchez Sara Rodriguez-Enriquez Rhys Pritchard School of Medical Science Griffith UniversitySouthport 4222Gold CoastAustralia Departmento de Bioquímica Instituto Nacional de CardiologiaTlalpan 14080Mexico

Intermittent hypoxia within tumor microenvironments causes pro-oxidative stress impairing oxidative phos-phorylation(OxPhos)and increases mitochondrial production of reactive oxygen species(ROS).In primary tu-mors this provokes metabolic reprogramming of both tumor cells and cancer stem cells and emergence of highly metastatic cancer *** reprogramming is initiated by activating nuclear respiratory factors and hypoxia-inducible factors in response to changes in oxygen and ROS ***,hypoxia-induced pro-oxidative stress drives invasion and ***,it is also the Achilles’heel of metastatic cancer cells because pro-oxi-dative agents further overload the mitochondria and intracellular milieu with excessive ROS to trigger apoptosis,whereas antioxidant agents promote their survival and tumor *** lies the metastatic tumor cell sensitivity to non-steroidal anti-inflammatory drugs(NSAIDs)and we and others have shown that the NSAID celecoxib exerts powerful pro-oxidative anticancer effects by directly targeting mitochondria to increase ROS production and trigger cancer cell death,including metastatic cancer cells and cancer stem *** review highlights the considerable benefits from appropriate NSAID use in humans against post-diagnosis metastatic tumors and the need to further develop their use as adjuvant therapy for advanced stage metastatic disease where they are already showing significantly improved clinical outcomes.

关键词： Non-steroidal anti-inflammatory drug celecoxib metastasis anticancer mitocans chemosensitizing cancer stem cells therapy

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