Abstract
Antimicrobial peptides (AMPs) are part of the innate immune defense mechanism of many organisms. Although AMPs have been essentially studied and developed as potential alternatives for fighting infectious diseases, their use as anticancer peptides (ACPs) in cancer therapy either alone or in combination with other conventional drugs has been regarded as a therapeutic strategy to explore. As human cancer remains a cause of high morbidity and mortality worldwide, an urgent need of new, selective, and more efficient drugs is evident. Even though ACPs are expected to be selective toward tumor cells without impairing the normal body physiological functions, the development of a selective ACP has been a challenge. It is not yet possible to predict antitumor activity based on ACPs structures. ACPs are unique molecules when compared to the actual chemotherapeutic arsenal available for cancer treatment and display a variety of modes of action which in some types of cancer seem to co-exist. Regardless the debate surrounding the definition of structure-activity relationships for ACPs, great effort has been invested in ACP design and the challenge of improving effective killing of tumor cells remains. As detailed studies on ACPs mechanisms of action are crucial for optimizing drug development, in this review we provide an overview of the literature concerning peptides' structure, modes of action, selectivity, and efficacy and also summarize some of the many ACPs studied and/or developed for targeting different solid and hematologic malignancies with special emphasis on the first group. Strategies described for drug development and for increasing peptide selectivity toward specific cells while reducing toxicity are also discussed.
Highlights
LEADING ANTIMICROBIAL PEPTIDES INTO ANTICANCER THERAPY Inappropriate and irrational use of antibiotics has induced the worldwide emergence and spreading of resistant microorganisms
Antimicrobial peptides constitute a mechanism of immune defense with low antigenicity (Iwasaki et al, 2009) that can be found in innumerous eukaryotic organisms of different species (Reddy et al, 2004)
The results showed a selective cytotoxic activity dependent on the negative charge of the cancer cell membrane and PS, providing direct proof of PS role in the anticancer activity (Iwasaki et al, 2009)
Summary
LEADING ANTIMICROBIAL PEPTIDES INTO ANTICANCER THERAPY Inappropriate and irrational use of antibiotics has induced the worldwide emergence and spreading of resistant microorganisms. Prostate, uterine cervix, liver and lung are some of the targeted tumors for the development of ACPs. Some of these peptides defy the malignant cells by apoptotic or necrotic mechanisms after damaging cellular membranes, others by intracellular targets and it is possible that one single peptide presents more than one mode of anticancer activity.
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