[Host defense peptides and peptidomimetics as new weapons for cancer treatment].
Host defence peptides (HDP) produced by almost all species of living organisms and widely recognized as antimicrobial antibiotics have also proved to be capable of killing a wide variety of cancer cells. In this respect they have many advantages over conventional cytotoxic chemotherapeutic agents. They seem to kill cancer cells by effects on plasma membranes and/or the membranes of mitochondria. They are often effective against multidrug-resistant cells. They have a broad spectrum of activity in that their killing effects are not restricted to particular kinds of cancer. Above all they commonly have few side effects in that they do not have the same detrimental effects on normal cells as they do on cancer cells. It has been demonstrated that HDP can be used as effective adjuvants to conventional chemotherapeutic agents. In addition they have effects on neo-angiogenesis which is important in relation to tumour growth. HDP have been shown to be powerful immunomodulators in a number of circumstances and in this respect they are believed to be instrumental in strengthening immunological host defence against cancer cells. Importantly it has also been shown that certain HDP have the capability to alter the capacity of cells to import Ca ions by affecting the location and thus function of calreticulin. Such changes it has been argued are significant in facilitating the killing of tumour cells by immunogical means. HDP constitute a novel class of anticancer agents for which, as we develop better knowledge of their pharmacokinetic profiles and learn better how to tailor their administration, hold high promise to augment or even replace the currently available cytotoxic anticancer chemotherapeutic agents most of which owe their efficacy to their capacity to bind to and damage target cell DNA.
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Semmelweis Egyetem, AOK I. sz. Patológiai és Kísérleti Rákkutató Intézet, 1085 Budapest, Ulloi út 26. lapkar@t-online.hu
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D010455:Peptides / Q000494:pharmacology* / Q000627:therapeutic use*
D000903:Antibiotics, Antineoplastic; D023181:Antimicrobial Cationic Peptides; D000970:Antineoplastic Agents; D007155:Immunologic Factors; D010455:Peptides