King cobra (
Ophiophagus hannah) venom L-amino acid oxidase (LAAO), a heat-stable
enzyme, is an extremely potent antiproliferative agent against
cancer cells when compared with LAAO isolated from other
snake venoms.
King cobra venom LAAO was shown to exhibit very strong antiproliferative activities against MCF-7 (human breast
adenocarcinoma) and A549 (human
lung adenocarcinoma) cells, with an IC50 value of 0.04±0.00 and 0.05±0.00 μg/mL, respectively, after 72-hr treatment. In comparison, its cytotoxicity was about 3-4 times lower when tested against human non-tumourigenic breast (184B5) and lung (NL 20) cells, suggesting selective antitumour activity. Furthermore, its potency in MCF-7 and A549 cell lines was greater than the effects of
doxorubicin, a clinically established
cancer chemotherapeutic agent, which showed an IC50 value of 0.18±0.03 and 0.63±0.21 μg/mL, respectively, against the two cell lines. The selective cytotoxic action of the LAAO was confirmed by
phycoerythrin (PE)
annexin V/7-amino-
actinomycin (AAD) apoptotic assay, in which a significant increase in apoptotic cells was observed in LAAO-treated tumour cells than in their non-tumourigenic counterparts. The ability of LAAO to induce apoptosis in tumour cells was further demonstrated using
caspase-3/7 and DNA fragmentation assays. We also determined that this
enzyme may target oxidative stress in its killing of tumour cells, as its cytotoxicity was significantly reduced in the presence of
catalase (a H2O2 scavenger). In view of its heat stability and selective and potent cytotoxic action on
cancer cells,
king cobra venom LAAO can be potentially developed for treating solid tumours.