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NEW RELEASE:
GHK Enhances
Mesenchymal Stem Cells
Osteogenesis
Acta Biomaterialia (2019)
Self-Assembled
Antibacterial GHK-Cu
Nanoparticles for
Wound Healing
Particle & Particle (2019)
Effect of GHK-Cu
on Stem Cells and
Relevant Genes
OBM Geriatrics
(2018)
GHK Alleviates
Neuronal Apoptosis Due
to Brain Hemorrhage
Frontiers in Neuroscience
(2018)
GHK-Cu:
Endogenous Antioxidant
International Journal of Pathophysiology and Pharmacology (2018)
Regenerative and
Protective Actions of
GHK-Cu Peptide
International Journal of
Molecular Sciences
(2018)
Skin Regenerative and
Anti-Cancer Actions
of Copper Peptides
Cosmetics
(2018)
GHK-Cu Accelerates
Scald Wound Healing
Promoting Angiogenesis
Wound Repair and
Regeneration
(2017)

GHK Peptide Inhibits
Pulmonary Fibrosis
by Suppressing TGF-β1
Frontiers in Pharmacology
(2017)
UNITED STATES PATENT:
Non-Toxic
Skin Cancer Therapy
with Copper Peptides
(2017)
The Effect of Human
Peptide GHK Relevant to
Nervous System Function
and Cognitive Decline
Brain Sciences (2017)
Effects of Tripeptide
GHK in Pain-Induced
Aggressive Behavior
Bulletin of Experimental
Biology & Medicine
(2017)
GHK-Cu Elicits
In Vitro Alterations
in Extracellular Matrix
Am Journal of Respiratory
and Critical Care Medicine

(2017)
Selected Biomarkers &
Copper Compounds
Scientific Reports

(2016)
GHK-Cu on Collagen,
Elastin, and Facial Wrinkles
Journal of Aging Science
(2016)
Tri-Peptide GHK-Cu
and Acute Lung Injury
Oncotarget
(2016)

Effect of GHK Peptide
on Pain Sensitivity
Experimental
Pharmacology
(2015)

New Data of the
Cosmeceutical
and TriPeptide GHK
SOFW Journal
(2015)
GHK Peptide as a
Natural Modulator of
Multiple Cellular Pathways
in Skin Regeneration
BioMed Research (2015)
Resetting Skin Genome
Back to Health
Naturally with GHK
Textbook of Aging Skin
(2015)
GHK-Cu May Prevent
Oxidative Stress in Skin
by Regulating Copper and
Modifying Expression of
Numerous Antioxidant Genes Cosmetics (2015)
GHK Increases
TGF-β1 in
Human Fibroblasts

Acta Poloniae
Pharmaceutica

(2014)
GHK:
The Human Skin Remodeling Peptide Induces Anti-Cancer
Expression and DNA Repair Analytical Oncology
(2014)
GHK & DNA:
Resetting the
Human Genome to Health
BioMed Research
International
(2014)
Enhanced Tropic Factor Secretion of Mesenchymal
Stem Cells with GHK
Acta Biomater
(2014)
Anxiolytic (Anti-Anxiety)
Effects of GHK Peptide
Bulletin of Experimental
Biology & Medicine
(2014)
Emphysema-Related
Lung Destruction and
its Reversal by GHK
Genome Medicine
(2012)
TriPeptide GHK Induces
Programmed Cell Death
of Neuroblastoma
Journal of Biotechnology
(2012)
Stem Cell
Recovering Effect
of GHK in Skin
Peptide Science
(2012)
Skin Penetration of
Copper Tripeptide in Vitro
Journal of International
Inflammation Research
(2010)
Possible Therapeutics
for Colorectal Cancer
Journal of Clinical and
Experimental Metastasis
(2010)
UNITED STATES PATENT:
Methods of Controlling
Differentiation and
Proliferation of Stem Cells
(2005)
Effects of
Copper Tripeptide
on Irradiated Fibroblasts
American Medical Association
(2005)
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GHK, the Human Skin Remodeling Peptide, Induces Anti-Cancer Expression of Numerous Caspase, Growth Regulatory, and DNA Repair Genes

Abstract: GHK (glycyl-L-histidyl-L-lysine) is a human plasma copper-binding peptide that declines during aging. Numerous studies have established many biological actions of GHK: it improves tissue regeneration, possesses anti-oxidant and anti-inflammatory effects, increases cellular stemness; increases decorin, angiogenesis, and nerve outgrowth. In recent studies, GHK was found to switch gene expression from a diseased state to a healthier state for certain cancers and for chronic obstructive pulmonary disease. In studies of aggressive, metastatic human colon cancer, the Broad Institute's Connectivity Map indicated that GHK, out of 1,309 bioactive molecules studied, reversed the expression of 70% of 54 genes over-expressed genes. GHK also reactivates programmed cell death in several cultured human cancer lines.

To determine GHK's potential as a cancer treatment, we analyzed the molecule's effect on the human gene expression using the Connectivity Map. GHK induces a 50% or greater change of expression in 31.2% of human genes. GHK increased gene expression in 6 of the 12 human caspase genes that activate programmed cell death. In 28 other genes, GHK altered the pattern of gene expression in a manner that would be expected to inhibit cancer growth. For DNA repair genes, there was a one-sided increase in the expression of such genes (47 UP, 5 DOWN).

A previous study found that a copper peptide plus ascorbic acid inhibited Ehrlich ascites cancer in mice. Using this method with GHK-copper gave a strong suppression of Sarcoma 180 in mice. These results support the idea that GHK may help to impede or suppress cancer growth.

GHK and DNA Repair Genes

Using NetAffx Analysis Center (http://www. affymetrix.com), the annotations for each probe set in the GeneChip HT Human Genome U133A Array were retrieved. Searching the Gene Ontology (GO) descriptions for the term DNA Repair resulted in 497 probe sets (313 genes). GHK stimulates many DNA repair genes. Gene expression is increased in 47 genes and decreased in 5 genes see Tables 5 and 6. Cell culture results also suggest that GHK activates DNA repair. Anti-cancer radiation therapy damages cellular DNA and slows cell replication. GHK-Copper at 1 nanomolar restored normal growth rates to radiation damaged cells.

Table 5: GHK is Primarily Stimulatory on DNA Repair Genes


Percent Change in Gene Expression

Genes UP


Genes DOWN

50% - 100%

41

4

100% - 150%

2

1

150% - 200%

1

0

200% - 250%

2

0

250% - 300%

1

0




Table 6: Most Affected DNA Repair Genes


UP

Gene Title


Percent Change
in Gene Expression

1

poly (ADP-ribose) polymerase family, member 3, PARP3

253

2

polymerase (DNA directed), mu, POLM

225

3

MRE11 meiotic recombination 11 homolog A MRE11A

212

4

RAD50 homolog (S. cerevisiae), RAD50

175

5

eyes absent homolog 3 (Drosophila), EYA3

128

6

retinoic acid receptor, alpha, RARA

123

DOWN

 

 

1

cholinergic receptor, nicotinic, alpha 4, CHRNA4

-105

 

 


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