Therapeutic approaches to the modulation of apoptosis

Abstract

The appreciation of the role of apoptosis in the vast majority of diseases affecting humans has revolutionized the discovery and development of drugs targeting inflammation and oncology. Novel therapeutic approaches to modulate disease by regulating apoptosis are currently being tested in preclinical and clinical settings. Enthusiasm for some of these therapies is reflected in the fact that they have received U.S. Food and Drug Administration approval in record time. Approaches include the traditional use of small molecules to target specific players in the apoptosis cascade. They also include radical new approaches such as using antisense molecules to inhibit production of the Bcl-2 protein or antibodies that ligate either death receptors, such as TRAIL (tumour necrosis factor-related apoptosis-inducing ligand), or the MHC (HLA-DR), resulting in the initiation of apoptosis of target cells. Antibodies targeting cell-specific antigens are being used in conjunction with radioactive isotopes to deliver a more specific chemotherapy, particularly in the case of B-cell lymphomas. Other therapies target mitochondria, a key organelle in the apoptosis cascade. This diverse range of therapies includes photodynamic therapy, retinoic acid and arsenic trioxide, all of which induce apoptosis by generating reactive oxygen species. As our understanding of apoptosis increases, further opportunities will arise for tailor-made therapies that will result in improved clinical outcome without the devastating side effects of current interventions.

Exogenous spermidine, arsenic and β-aminobutyric acid modulate tobacco resistance to tobacco mosaic virus, and affect local and systemic glucosylsalicylic acid levels and arginine decarboxylase gene expression in tobacco leaves

“…The hormesis dose-response phenomenon, characterized by a low-dose stimulation and a high-dose inhibition of a given parameter, has been reported previously for As (Calabrese and Blain, 2004), and supports the hypothesis that this metalloid plays a role in induced resistance. Moreover, it is well documented in animal systems that, through the induction of ROS, As mediates apoptosis (Murphy et al, 2003), which has similarities with plant cell death pathways (Hofius et al, 2007). ROS are also major components of the initial plant response against invading pathogens (Torres et al, 2006).…”

Macrophage Apoptosis in Tuberculosis

“…There is active investigation and development of drugs to regulate cell death responses for therapeutic indications including cancer, cardiovascular disease, neurodegenerative diseases, and aging among others 66,67. Drugs that enhance classical apoptosis or those that inhibit the high-MOI death mode could have therapeutic value, while those with opposite effects could be detrimental to host defense in TB.…”

Inflammation pro-resolving potential of 3,4-dihydroxyacetophenone through 15-deoxy-Δ12,14-prostaglandin J2 in murine macrophages

“…As the regulative target of DHAP, 15dPGJ 2 was also partly mediated its function to inhibit TNF-alpha and enhance apoptosis. More and more researchers believe developing drugs based on endogenous mediators that are inherent to resolution might represent a new but attractive strategy in anti-inflammatory therapy [31,32] Unfortunately, such therapeutics, with the exception of those that regulate leukocyte apoptosis [33], is far from the clinic applications [9]. Thus, our results might give a clue for the future research on the pharmacologic effect of some anti-inflammatory Chinese Herbs.…”