Oncol Rep. 2016 Sep;36(3):1457-66. doi: 10.3892/or.2016.4914. Epub 2016 Jul 5.
1School of Life Sciences, The Chinese University of Hong Kong, NT, Hong Kong, SAR, P.R. China.
Abstract
Current treatment strategies for lung cancer
cause undesirable side‑effects. Integrated medicine with a curative
approach has become a common approach to the treatment strategy. Recent
studies suggest that American alligator blood is effective in reducing colorectal cancer
cell viability in vitro, but the mechanism remains unclear. In the
present study, we aimed to study the anticancer activity of crocodile
blood extracts on lung cancer
cell line A549 and investigate the possible mechanisms involved.
In vitro studies were utilized to investigate the effects on the cancer
cells after incubation with the blood extracts. The active fraction
that showed more efficacy in inhibiting cell growth was characterized in
the supernatant (S2) from whole blood extracts. High performance liquid
chromatography (HPLC) analysis revealed that S2 contained more polar
moiety from whole blood. S2 induced DNA fragmentation. Cell cycle arrest
in the G1/M phase was demonstrated and mitochondrial membrane
permeability was disrupted. An increase in the generation of reactive
oxygen species (ROS) and increased activities of caspase-3 and caspase-7
were detected. Furthermore, release of cytochrome c, upregulation of
expression of Bax, p53, p21, Bid, cleaved forms of the caspase family
and PARP along with downregulation of Bcl-2, PCNA, MDM2, caspase‑8, wild
types of caspase family proteins and PARP were recorded after treatment
with S2 fractions. Moreover, the PI3K/AKT survival pathway was
downregulated by S2 fractions in the lung cancer cell line.