GHK, the Human Skin Remodeling Peptide, Induces Anti-Cancer Expression of Numerous Caspase, Growth Regulatory, and DNA Repair Genes
Pages 79-87
Loren Pickart, Jessica M. Vasquez-Soltero, Francoise D. Pickart and John Majnarich
DOI: http://dx.doi.org/10.6000/1927-7229.2014.03.02.2
Published: 30 April 2014

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.

Keywords: Copper peptides, cancer therapy, cancer inhibition, sarcoma, connectivity map.

‘Hygienic’ Lymphocytes Convey Increased Cancer Risk
Pages 113-121
Tatiana Levkovich, Theofilos Poutahidis, Kelsey Cappelle, Mark B. Smith, Allison Perrotta, Eric J. Alm and Susan E. Erdman
DOI: http://dx.doi.org/10.6000/1927-7229.2014.03.03.1
Published: 12 August 2014

Abstract: Risk of developing inflammation-associated cancers has increased in industrialized countries during the past 30 years. One possible explanation is societal hygiene practices with use of antibiotics and Caesarian births that provide too few early life exposures of beneficial microbes. Building upon a ‘hygiene hypothesis’ model whereby prior microbial exposures lead to beneficial changes in CD4+ lymphocytes, here we use an adoptive cell transfer model and find that too few prior microbe exposures alternatively result in increased inflammation-associated cancer growth in susceptible recipient mice. Specifically, purified CD4+ lymphocytes collected from ‘restricted flora’ donors increases multiplicity and features of malignancy in intestinal polyps of recipient Apc^Min/+ mice, coincident with increased inflammatory cell infiltrates and instability of the intestinal microbiota. We conclude that while a competent immune system serves to maintain intestinal homeostasis and good health, under hygienic rearing conditions CD4+ lymphocytes instead exacerbate inflammation-associated tumorigenesis, subsequently contributing to more frequent cancers in industrialized societies.