This information is for the use of medical researchers and persons interested in health sciences. It must be emphasized that GHK and other copper binding peptides have not been tested on human cancers and are not approved for such uses.

 

In 2010, Hong et al, using the the Broad Institute's Connectivity Map, predicted that GHK, at a low and non-toxic level, would reverse many of the effects of aggressive, metastatic human colon cancer on 40 critical cancer-spreading genes.

 

The gene test used GHK without copper but it is likely that much of the GHK was converted to GHK-copper because of the extremely high affinity of GHK for copper. Part of this effect may have been due to GHK-copper's effect on increasing the protein Decorin (named because it "decorates" the collagen strands). Decorin has a perplexing mixture of effects: Regeneration of muscles and nerves, reduction of scarring, and inhibition of tumor growth and cancer metastasis in animals.

 

The authors of this study searched for substances that could reverse expression of those genes involved in human colon cancer metastasis. To determine gene expression of human normal and cancerous cells, they measured RNA produced by cells. To find substances that can reverse expression of those genes involved in metastasis, they used very reliable database developed at the Broad Institute (Massachusetts Institute of Technology and Harvard) of 7000 genome wide expression profiles after treatment of 4 human cell lines with 1309 bioactive substances. Only two substances, GHK at 1 micromolar and securenine (an alkaloid) at 18 micromolar from the choice of 1309 were able to quiet down the genes involved in tumor spreading. The authors also mention low toxicity of GHK and the low concentration that produces desired effect.

 

Below is the abstact for this article:

 

A 'metastasis-prone' signature for early-stage mismatch-repair proficient sporadic colorectal cancer patients and its implications for possible therapeutics.

 

Hong Y, Downey T, Eu KW, Koh PK, Cheah PY.

 

Abstract

 

Metastasis is the major cause of cancer mortality. We aimed to find a metastasis-prone signature for early stage mismatch-repair proficient sporadic colorectal cancer (CRC) patients for better prognosis and informed use of adjuvant chemotherapy. The genome-wide expression profiles of 82 age-, ethnicity- and tissue-matched patients and healthy controls were analyzed using the Affymetrix U133 Plus 2 array. Metastasis-negative patients have 5 years or more of follow-up. A 10 x 10 two-level nested cross-validation design was used with several families of classification models to identify the optimal predictor for metastasis. The best classification model yielded a 54 gene-set (74 probe sets) with an estimated prediction accuracy of 71%. The specificity, sensitivity, negative and positive predictive values of the signature are 0.88, 0.58, 0.84 and 0.65, respectively, indicating that the gene-set can improve prognosis for early stage sporadic CRC patients. These 54 genes, including node molecules YWHAB, MAP3K5, LMNA, APP, GNAQ, F3, NFATC2, and TGM2, integrate multiple bio-functions in various compartments into an intricate molecular network, suggesting that cell-wide perturbations are involved in metastasis transformation. Further, querying the ;Connectivity Map' with a subset (70%) of these genes shows that Gly-His-Lys and securinine could reverse the differential expressions of these genes significantly, suggesting that they have combinatorial therapeutic effect on the metastasis-prone patients. These two perturbagens promote wound-healing, extracellular matrix remodeling and macrophage activation thus highlighting the importance of these pathways in metastasis suppression for early-stage CRC.

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