The use of small
antimicrobial peptides or
bacteriocins, like
nisin, to treat
cancer is a new approach that holds great promise.
Nisin exemplifies this new approach because it has been used safely in humans for many years as a food preservative, and recent laboratory studies support its anti-
tumor potential in
head and neck cancer. Previously, we showed that
nisin (2.5%, low content) has antitumor potential in
head and neck squamous cell carcinoma (
HNSCC) in vitro and in vivo. The current studies explored a naturally occurring variant of
nisin (
nisin ZP; 95%, high content) for its antitumor effects in vitro and in vivo.
Nisin ZP induced the greatest level of apoptosis in
HNSCC cells compared to low content
nisin.
HNSCC cells treated with increasing concentrations of
nisin ZP exhibited increasing levels of apoptosis and decreasing levels of cell proliferation, clonogenic capacity, and sphere formation.
Nisin ZP induced apoptosis through a
calpain-dependent pathway in
HNSCC cells but not in human oral keratinocytes.
Nisin ZP also induced apoptosis dose-dependently in human umbilical vein endothelial cells (HUVEC) with concomitant decreases in vascular sprout formation in vitro and reduced intratumoral microvessel density in vivo.
Nisin ZP reduced
tumorigenesis in vivo and long-term treatment with
nisin ZP extended survival. In addition,
nisin treated mice exhibited normal organ histology with no evidence of
inflammation,
fibrosis or
necrosis. In summary,
nisin ZP exhibits greater antitumor effects than low content
nisin, and thus has the potential to serve as a novel therapeutic for
HNSCC.