King cobra (
Ophiophagus hannah) venom L-amino acid oxidase (
OH-LAAO), a heat stable
enzyme, has been shown to exhibit very potent anti-proliferative activity against human breast and lung tumorigenic cells but not in their non-tumorigenic counterparts. We further examine its in vitro and in vivo anti-
tumor activity in a human prostate
adenocarcinoma (PC-3) model.
OH-LAAO demonstrated potent cytotoxicity against PC-3 cells with IC50 of 0.05 µg/mL after 72 h incubation in vitro. It induced apoptosis as evidenced with an increase in
caspase-3/7 cleavages and an increase in
annexin V-stained cells. To examine its in vivo anti-
tumor activity, we treated PC-3
tumor xenograft implanted subcutaneously in immunodeficient NU/NU (nude) mice with 1 µg/g
OH-LAAO given intraperitoneally (i.p.). After 8 weeks of treatment,
OH-LAAO treated PC-3
tumors were markedly inhibited, when compared to the control group (P <0.05). TUNEL staining analysis on the
tumor sections showed a significantly increase of apoptotic cells in the LAAO-treated animals. Histological examinations of the vital organs in these two groups showed no significant differences with normal tissues, indicating no obvious tissue damage. The treatment also did not cause any significant changes on the
body weight of the mice during the duration of the study. These observations suggest that
OH-LAAO cytotoxic effects may be specific to
tumor xenografts and less to normal organs. Given its potent anti-
tumor activities shown in vitro as well as in vivo, the
king cobra venom LAAO can potentially be developed to treat
prostate cancer and other solid
tumors.