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Cell-centric view of apoptosis and apoptotic cell death-inducing antitumoral strategies.

Apraiz A, Boyano MD, Asumendi A - Cancers (Basel) (2011)

Bottom Line: In this context, an extensive description of pathway-connections is necessary in order to point out the main regulatory molecules as well as to select the most appropriate therapeutic targets.In fact, tumor cell plasticity represents a major challenge in chemotherapy and improvement on anticancer therapies seems to rely on appropriate drug combinations.An overview of the current status regarding apoptotic pathways as well as available chemotherapeutic compounds provides a new perspective of possible future anticancer strategies.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology and Histology, School of Medicine and Dentistry, University of the Basque Country, 48940, Leioa (Bizkaia), Spain. aintzane.asumendi@ehu.es.

ABSTRACT
Programmed cell death and especially apoptotic cell death, occurs under physiological conditions and is also desirable under pathological circumstances. However, the more we learn about cellular signaling cascades, the less plausible it becomes to find restricted and well-limited signaling pathways. In this context, an extensive description of pathway-connections is necessary in order to point out the main regulatory molecules as well as to select the most appropriate therapeutic targets. On the other hand, irregularities in programmed cell death pathways often lead to tumor development and cancer-related mortality is projected to continue increasing despite the effort to develop more active and selective antitumoral compounds. In fact, tumor cell plasticity represents a major challenge in chemotherapy and improvement on anticancer therapies seems to rely on appropriate drug combinations. An overview of the current status regarding apoptotic pathways as well as available chemotherapeutic compounds provides a new perspective of possible future anticancer strategies.

No MeSH data available.


Related in: MedlinePlus

Comparison of the classical (left side) and novel models (right side) of the mitochondrial permeability transition pore (PTP). The role of hexokinase (HK), peripheral-type benzoazepine receptor (PBR) and mitochondrial phosphate carrier (PiC) in the mitochondrial transition pore formation/function are still controversial [27,31].
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f3-cancers-03-01042: Comparison of the classical (left side) and novel models (right side) of the mitochondrial permeability transition pore (PTP). The role of hexokinase (HK), peripheral-type benzoazepine receptor (PBR) and mitochondrial phosphate carrier (PiC) in the mitochondrial transition pore formation/function are still controversial [27,31].

Mentions: According to the classically accepted, though controversial, model, mitochondrial permeability transition (MPT) is based on opening of the PTP protein complex. Classical (vs. newly proposed) PTP (Figure 3) is a protein complex formed by the voltage-dependent anion channel (VDAC) located in the mitochondrial OM, the adenine nucleotide translocator (ANT) in the mitochondrial IM, cyclophilin D (CypD) in the mitochondrial matrix, and several other proteins at contact sites between the mitochondrial outer and inner membranes [26,27]. Despite the fact that most of the data are from in vitro studies, cytosolic Ca2+, low ATP, and reactive oxygen species (ROS) are the most accepted inducers of PTP opening, whereas cyclosporin A reverts the opening in most cases by sequestering CyD in the mitochondrial matrix [27]. Current data, however, indicate that VDAC is dispensable for MPT-mediated cell death [28]; on the other hand, CyD is gaining importance in mitochondria-mediated cell death and especially, in ischaemia/reperfusion-mediated cardiac injury [29,30]. Nevertheless, recent studies indicate that CyD is not a common mediator in mitochondrial-mediated apoptosis and may be primarily involved in ROS or Ca2+ overload-induced necrotic cell death [30].


Cell-centric view of apoptosis and apoptotic cell death-inducing antitumoral strategies.

Apraiz A, Boyano MD, Asumendi A - Cancers (Basel) (2011)

Comparison of the classical (left side) and novel models (right side) of the mitochondrial permeability transition pore (PTP). The role of hexokinase (HK), peripheral-type benzoazepine receptor (PBR) and mitochondrial phosphate carrier (PiC) in the mitochondrial transition pore formation/function are still controversial [27,31].
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3756403&req=5

f3-cancers-03-01042: Comparison of the classical (left side) and novel models (right side) of the mitochondrial permeability transition pore (PTP). The role of hexokinase (HK), peripheral-type benzoazepine receptor (PBR) and mitochondrial phosphate carrier (PiC) in the mitochondrial transition pore formation/function are still controversial [27,31].
Mentions: According to the classically accepted, though controversial, model, mitochondrial permeability transition (MPT) is based on opening of the PTP protein complex. Classical (vs. newly proposed) PTP (Figure 3) is a protein complex formed by the voltage-dependent anion channel (VDAC) located in the mitochondrial OM, the adenine nucleotide translocator (ANT) in the mitochondrial IM, cyclophilin D (CypD) in the mitochondrial matrix, and several other proteins at contact sites between the mitochondrial outer and inner membranes [26,27]. Despite the fact that most of the data are from in vitro studies, cytosolic Ca2+, low ATP, and reactive oxygen species (ROS) are the most accepted inducers of PTP opening, whereas cyclosporin A reverts the opening in most cases by sequestering CyD in the mitochondrial matrix [27]. Current data, however, indicate that VDAC is dispensable for MPT-mediated cell death [28]; on the other hand, CyD is gaining importance in mitochondria-mediated cell death and especially, in ischaemia/reperfusion-mediated cardiac injury [29,30]. Nevertheless, recent studies indicate that CyD is not a common mediator in mitochondrial-mediated apoptosis and may be primarily involved in ROS or Ca2+ overload-induced necrotic cell death [30].

Bottom Line: In this context, an extensive description of pathway-connections is necessary in order to point out the main regulatory molecules as well as to select the most appropriate therapeutic targets.In fact, tumor cell plasticity represents a major challenge in chemotherapy and improvement on anticancer therapies seems to rely on appropriate drug combinations.An overview of the current status regarding apoptotic pathways as well as available chemotherapeutic compounds provides a new perspective of possible future anticancer strategies.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology and Histology, School of Medicine and Dentistry, University of the Basque Country, 48940, Leioa (Bizkaia), Spain. aintzane.asumendi@ehu.es.

ABSTRACT
Programmed cell death and especially apoptotic cell death, occurs under physiological conditions and is also desirable under pathological circumstances. However, the more we learn about cellular signaling cascades, the less plausible it becomes to find restricted and well-limited signaling pathways. In this context, an extensive description of pathway-connections is necessary in order to point out the main regulatory molecules as well as to select the most appropriate therapeutic targets. On the other hand, irregularities in programmed cell death pathways often lead to tumor development and cancer-related mortality is projected to continue increasing despite the effort to develop more active and selective antitumoral compounds. In fact, tumor cell plasticity represents a major challenge in chemotherapy and improvement on anticancer therapies seems to rely on appropriate drug combinations. An overview of the current status regarding apoptotic pathways as well as available chemotherapeutic compounds provides a new perspective of possible future anticancer strategies.

No MeSH data available.


Related in: MedlinePlus