Anti-
cancer peptides (ACPs) are small cationic and hydrophobic
peptides that are more toxic to
cancer cells than normal cells. ACPs kill
cancer cells by causing irreparable membrane damage and cell lysis, or by inducing apoptosis. Direct-acting ACPs do not bind to a unique receptor, but are rather attracted to several different molecules on the surface of
cancer cells. Here we report that an amidated
wasp venom peptide,
Mastoparan, exhibited potent anti-
cancer activities toward
leukemia (IC50~8-9.2μM), myeloma (IC50~11μM), and
breast cancer cells (IC50~20-24μM), including multidrug resistant and slow growing
cancer cells. Importantly, the potency and mechanism of
cancer cell killing was related to the amidation of the C-terminal carboxyl group.
Mastoparan was less toxic to normal cells than it was to
cancer cells (e.g., IC50 to PBMC=48μM).
Mastoparan killed
cancer cells by a lytic mechanism. Moreover,
Mastoparan enhanced
etoposide-induced cell death in vitro. Our data also suggest that
Mastoparan and
gemcitabine work synergistically in a mouse model of mammary
carcinoma. Collectively, these data demonstrate that
Mastoparan is a broad-spectrum, direct-acting ACP that warrants additional study as a new therapeutic agent for the treatment of various
cancers.