Molecular Markers that Can Be Utilized in Diet and Dietary Supplement Research




Prostate and other cancers have a multitude of potential markers that can be used in laboratory and clinical studies of diet and dietary supplement interventions. More overt clinical markers include imaging tests, biopsy samples, prostate-specific antigen kinetics, and urinary testing. Many molecular markers are currently available, including antiapoptotic and apoptotic proteins, cell adhesion molecules, cell cycle compounds, growth factors, angiogenic markers, and proliferative and inflammatory signals. Protein kinases and transcription factors should also be considered for diversity. Testing of numerous molecular markers has become critical in gaining preliminary insight into the potential impact of a novel diet and supplemental agents.


So many markers and so little time and financing should be the new adage. Prostate and other cancers have a multitude of potential markers that can be used in studies, including those that test diet and dietary supplement interventions. More overt clinical markers include imaging tests, biopsy results, and prostate-specific antigen kinetics. However, because it is not realistic to follow men in clinical trials for decades on nutritional interventions, researchers are relying on numerous molecular markers to access the potential impact of interventions on urological and other cancers. This article briefly reviews some of the diverse markers that may be considered by a researcher for use in a clinical study.


Antiapoptotic proteins


When affected favorably by diet and dietary supplements or another intervention, there should be a downregulation of antiapoptotic proteins, because upregulation or overexpression of these proteins promotes cancer cell survival, resistance to conventional treatments, and progression. Examples of common antiapoptotic proteins used in studies include Bcl-2 (B-cell lymphoma 2), Bcl-XL, Bfl1/A1, c-FLIP (cellular FLICE inhibitory pathway) that contains multiple apoptosis inhibitors, cIAP (cellular inhibitor of apoptosis), survivin, TRAF1 (tumor necrosis factor receptor–associated factor), and XIAP (X-linked inhibitor of apoptosis).




Apoptotic proteins


These proteins need to be upregulated or hyperactivated in diet and supplement studies, because potentially more apoptosis of unhealthy or malignant cells would occur if the intervention had a positive impact. Examples of apoptotic proteins include Bax, caspase (2, 3, 7, 9, and so forth), and PARP (poly(ADP-ribose) polymerase 1).




Apoptotic proteins


These proteins need to be upregulated or hyperactivated in diet and supplement studies, because potentially more apoptosis of unhealthy or malignant cells would occur if the intervention had a positive impact. Examples of apoptotic proteins include Bax, caspase (2, 3, 7, 9, and so forth), and PARP (poly(ADP-ribose) polymerase 1).




Cell adhesion molecules


Cell adhesion molecules (CAMs) and integrins are needed for the maintenance of the epithelium. An abnormality or insult in epithelial cell adhesion can lead to invasive and metastatic behavior whereby cells invade the basement membrane and access the stroma. Loss of adhesion molecules is more characteristic of aggressiveness, but so is the overexpression of some of these molecules. Moreover, effective interventions appear to maintain or restore CAMs in some instances. Multiple CAMs exist, including ELAM (endothelial leukocyte adhesion molecule), ICAM-1 (intercellular cell adhesion molecule 1), VCAM (vascular cellular adhesion molecule), cadherins, and integrins.




Cell cycle proteins


Cell cycle proteins are switches that allow the cell cycle or replication to continue, cease, or even discontinue. An intervention that favorably affects the cell cycle is of enormous interest. Several commonly tested cell cycle proteins include CDK (cyclin-dependent kinase), cyclins, p21, p27, and p57.




Growth factors/angiogenesis/proliferation/inflammatory compounds


Agents such as celecoxib that can downregulate growth factors or markers of inflammation may have anticancer activity. The potential benefits or lack of benefit of fish oil has been studied via COX-2 (cyclooxygenase-2), IL (interleukin)-6, and TNF-α (tumor necrosis factor α) pathways.


Reductions or downregulation of growth factors appears to be a favorable sign for a diet or dietary intervention. Some examples of compounds in this category include COX-2, EGF (epidermal growth factor), erythropoietin and receptor, Ki67, FGF (fibroblast growth factor), IGF (insulin-like growth factor), IL-1, IL-6, IL-8, PDGF (platelet-derived growth factor), TGF-β (transforming growth factor β), TNF-α, and VEGF (vascular endothelial growth factor).




Miscellaneous


Protein kinases are enzymes that assist in modifying other proteins via phosphorylation and in some cases increasing aggressiveness. For example, upregulation of phosphorylated Akt may increase drug resistance, and similar concerns occur with HER-2 expression. Transcription factors such as NF-κB (nuclear factor κB) affect signaling that can lead to inflammation and cancer progression.




Summary


Urological cancers have a multitude of potential molecular markers that can be used in laboratory and clinical studies of diet and dietary supplement interventions ( Table 1 ). The decision as to which markers to use is difficult, but enough multiple diet and dietary supplement studies have been conducted over the past decade to allow researchers to compare results. Antiapoptotic and apoptotic proteins, CAMs, cell cycle compounds, growth factors, angiogenic markers, and proliferative and inflammatory signals have all been used in the past. Protein kinases and transcription factors should also be considered to gain a more diverse perspective. Testing with numerous molecular markers has become critical in gaining preliminary insight into the potential impact of a novel diet and supplemental agents.



Table 1

Molecular markers that could be used in diet and dietary supplement studies and cancer

























Marker for Study Examples
I. Antiapoptotic proteins (downregulation suggests a beneficial impact by an intervention) Bcl-2
Bcl-XL
Bfl1/A1
c-FLIP
cIAP
Survivin
TRAF1
XIAP
II. Apoptotic proteins (upregulation suggests a beneficial impact by an intervention) Bax
Caspase (2, 3, 7, 9, etc)
PARP
III. Cell adhesion molecules (upregulation of some and downregulation of others suggests a beneficial impact by an intervention) Cadherins
ELAM
ICAM-1
Integrins
VCAM
IV. Cell cycle proteins (upregulation of some and downregulation of others suggests a beneficial impact by an intervention) CDK
Cyclins
p21
p27
p57
V. Growth factors (down-regulation suggests a beneficial impact by an intervention) COX-2
EGF
Erythropoietin
Ki67
FGF
IGF
IL-1, IL-6, IL-8
PDGF
TGF-β
TNF
VEGF
VI. Miscellaneous(downregulation suggests a beneficial impact by an intervention, but there are exceptions) Protein kinases (Akt, HER2)
Transcription factors (NF-κB)



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Mar 11, 2017 | Posted by in UROLOGY | Comments Off on Molecular Markers that Can Be Utilized in Diet and Dietary Supplement Research

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