This month’s featured article is from the lab of Yide Qin of Anhui Medical University in Hefei, China. The article was published 24 March 2016 in the journal BMC Cancer. This study investigates the anti-cancer function and mechanisms of action of a milk-derived anti-cancer fusion peptide (ACFP). The authors built off of previous research into 2 milk peptides, LfcinB and PGPIPN. Acting alone, both of these peptides exhibited anti-cancer activity; however, they were not stable and had other properties that did not make them amenable to clinical use. By fusing regions of these 2 peptides, the authors created a molecule with structural stability and strong anti-cancer activity.
Primary ovarian cell lines were established from over 50 cancer patients, and importantly, ACFP significantly decreased the viability of these cells in a dose-dependent manner. The decrease in viability was further shown to be related to an increase in apoptosis brought on by ACFP treatment. To understand signaling pathways underlying these responses, the authors used Phalanx Biotech’s Human OneArray Whole Genome Microarray. ACFP treatment caused a potent transcriptomic response in the ovarian cancer cells. Pathway analysis of the differentially expressed genes revealed pathways involved in apoptosis, cell cycle, chemokine signaling and various metabolic pathways.
Next, the authors sought to validate their microarray data with qPCR, where they targeted genes involved in apoptosis and cell cycle regulation. These targets included bcl-x, bax, akt, caspase-3, and cyclinB1. The qPCR results were consistent with the microarray data – the genes showed changes in expression following ACFP treatment, sometimes in a dose- and/or time-dependent manner. Lastly, the authors showed that some of these same targets also showed changes on the protein level.
In conclusion, this study clearly demonstrated the anti-cancer activity of ACFP and the cellular signaling pathways underlying this activity. Given these results, ACFP certainly seems like a promising therapeutic for the treatment of ovarian cancer.
Zhou J et al. The milk-derived fusion peptide, ACFP, suppresses the growth of primary human ovarian cancer cells by regulating apoptotic gene expression and signaling pathways (2016). BMC Cancer 16: 246.