Introduction
Cancer is a multifactorial and complex disease, which presents different
clinical outcomes depending on the affected tissue and the genetic
background of the patient (Luo, Solimini,
& Elledge, 2009). Tumor cells express a variety of molecular targets
involved in cancer progression and exhibit a deregulation in normal
growth, proliferation and survival, among other vital functions
(Hanahan & Weinberg, 2011). Because of
its complexity, the huge variety of molecular targets involved and the
high variability in therapeutic response, cancer has become a health
problem worldwide and one the sickness most difficult to treat in the
21st century.
Commonly, traditional chemotherapeutical drugs target tumor cells by
disrupting necessary cell products, such as DNA, RNA, or proteins
(Huang et al., 2014). However,
chemotherapy is also insufficient and highly toxic, because it does not
specifically target tumor cells, causing many side effects in patients
(Amit & Hochberg, 2010). Additionally,
multidrug resistance (MDR) is the main reason by which chemotherapy
fails to cure patients (Huang et al.,
2014). Under these limitations, therapeutical strategies based on
peptides are receiving increased attention.
There are several advantages of peptides, such as the small size, easy
synthesis and modification, tumor penetrating ability and a good
biocompatibility (Wu et al., 2014). A
growing number of studies indicate that peptides may be beneficial for
drug discovery and development. Peptides offer minimal immunogenicity,
excellent tissue penetrability, low-cost manufacturability, and
relatively easy of modify to enhance in vivo stability and
biological activity, properties which make them ideal candidates for
cancer treatment (Yavari, Mahjub,
Saidijam, Raigani, & Soleimani, 2018).
Peptides have also demonstrated to play a role in cancer therapy,
including early diagnosis, prognostic predictors, and directly in the
treatment of cancer patients. Unlike other therapies, peptides seem to
be more effective due to their specificity. Recently, some peptide-based
treatments against cancer, such as peptide vaccines, have attracted
increased attention. Anticancer activity of different peptides is
attributed to a variety of mechanisms that restrict tumor growth.
(Borghouts, Kunz, & Groner, 2005).
CIGB-552 is a synthetic peptide “first-in-class” that increases the
level of the intracellular protein COMMD1 (Copper Metabolism Mur 1
Domain containing protein1) and inhibits the anti-apoptotic genes
regulated by Nuclear Factor κB (NF-κB). CIGB-552 leads to the selective
degradation of RelA, an NF-κB subunit, and induces apoptosis in multiple
types of tumor cells in the absence of toxicity to normal cells. In
addition, CIGB-552 inhibits the transcriptional activity of NF-κB
induced by TNF-α and IL-1β in human colon cancer cells. The mechanism of
action of CIGB-552 assumes a new-targeted anticancer therapy to regulate
oncogenic-inflammatory activity of NF-κB in cancer cells, providing
selectivity and specificity. This novel peptide has a potential
application against solid tumors and inflammation-associated cancer
including colorectal, breast and lung cancer, lymphomas and others.