“Mitochondria are emerging as idealized targets for anti-cancer drugs. One reason for this is that although these organelles are inherent to all cells, drugs are being developed that selectively target the mitochondria of malignant cells without adversely affecting those of normal cells. Such anticancer drugs destabilize cancer cell mitochondria and these compounds are referred to as mitocans, classified into several groups according to their mode of action and the location or nature of their specific drug targets. Many mitocans selectively interfere with the bioenergetic functions of cancer cell mitochondria, causing major disruptions often associated with ensuing overloads in ROS production leading to the induction of the intrinsic apoptotic pathway. This in-depth review describes the bases for the bioenergetic differences found between normal and cancer cell mitochondria, focusing on those essential changes occurring during malignancy that clinically may provide the most effective targets for mitocan development. A common theme emerging is that mitochondrially mediated ROS activation as a trigger for apoptosis offers a powerful basis for cancer therapy. Continued research in this area is likely to identify increasing numbers of novel agents that should prove highly effective against a variety of cancers with preferential toxicity towards malignant tissue, circumventing tumor resistance to the other more established therapeutic anti-cancer approaches”. Follow the links:
Bioenergetic pathways in tumor mitochondria as targets for cancer therapy and the importance of the ROS-induced apoptotic trigger
Choosing between glycolysis and oxidative phosphorylation: A tumor’s dilemma?
Targeting Cell Metabolism In Chronic Lymphocytic Leukaemia (CLL); A Viable Therapeutic Approach?
Stalling the Engine of Resistance: Targeting Cancer Metabolism to Overcome Therapeutic Resistance
Is Cancer a Metabolic Disease?
Cancer as a Metabolic Disease
Targeting mitochondria for cancer therapy
Mitochondrial permeability transition pore as a selective target for anti-cancer therapy
Mitochondrial uncoupling and the reprograming of intermediary metabolism in leukemia cells
Mitocans as Novel Agents for Anticancer Therapy: An Overview
Apoptosis: from biology to therapeutic targeting
Metabolic targets in the cross hairs
- Tagged Apoptosis, BCL2, BH3 Mimetic, Cancer, CLL, DCA, Glutathione, Methyl Jasmonate, mitochondrial permeability transition, Natural, PEITC, Reactive Oxygen Species
Methyl Jasmonate is a plant stress hormone that has significant anti-cancer properties. So how does MJ work? Let me count the ways. It arrests cell cycle, inhibiting cell growth and proliferation; causes cell death through the intrinsic/extrinsic pro-apoptotic, p53-independent apoptotic, and non-apoptotic (necrosis) pathways; detaches hexokinase from the voltage-dependent anion channel, dissociating glycolytic and mitochondrial functions, decreasing the mitochondrial membrane potential, favoring cytochrome c release and ATP depletion, activating pro-apoptotic and inactivating anti-apoptotic proteins; induces reactive oxygen species mediated responses; stimulates MAPK-stress signaling and redifferentiation in leukemia cells; inhibits overexpressed pro-inflammatory enzymes in cancer cells such as aldo-keto reductase 1 and 5-lipoxygenase; inhibits cell migration and shows antiangiogenic and anti-metastatic activities. The complete lack of toxicity to normal cells and the rapidity by which MJ causes damage to cancer cells, turns MJ into a promising anticancer agent that can be used alone or in combination with other agents.
Follow the links for the relevant research:
MJ modes of action
Methyl Jasmonate: Putative Mechanisms of Action on Cancer Cells Cycle, Metabolism, and Apoptosis
Jasmonates: Novel Anticancer Agents Acting Directly and Selectively on Human Cancer Cell Mitochondria