Cytotoxic membrane disruption via lytic
peptides is a well-recognized mechanism of immune surveillance for antifungal and antibacterial host protection. Naturally occurring lytic
peptides were shown to exhibit antitumor activity as well. Peptidyl membrane-interactive molecules (MIMs) are synthetic lytic
peptides specifically designed to maximize antitumor activity. We tested nine novel Peptidyl MIMs for activity against four
androgen-insensitive
prostate-cancer cell lines using a standard microculture tetrazolium (MTT) assay. Five Peptidyl MIMs known to form alpha-helical secondary structures were active against prostate
carcinoma and were chosen for further study. Three
peptides configured in beta-pleated sheets were noticeably less effective. Concentrations lethal to 50% of the
prostate-cancer cell lines treated (D50 values) with the five chosen Peptidyl MIMs ranged from 0.6 to 1.8 microM. For comparison, two alpha-helically structured
peptides,
D2A21 and DP1E, were tested on several other
cancer types: breast (n = 2), colon (n = 2). bladder, cervical and lung
carcinomas (n = 1 each). Resulting LD50 values obtained in
breast carcinoma cells were significantly higher (P < 0.05) than those observed in
prostate cancer cells. LD50 values recorded for
D2A21 and DP1E in cervical, colon, bladder, and
lung cancer lines were similar to those obtained in
prostate cancer cells. As compared with
cisplatin, a standard chemotherapeutic
drug, the LD50 values recorded for
D2A21 were significantly lower (P < 0.04) in
prostate-cancer cell lines, suggesting the therapeutic efficacy of Peptidyl MIMs. These data demonstrate for the first time the cytotoxic potential of Peptidyl MIMs against
prostate cancer cells and suggest a dependence on a specific secondary alpha-helical structure of the
peptide.