Background:
Cancer contributes to significant morbidity and mortality despite advances in treatment
and supportive care. There is a need for the identification of effective anticancer agents. Reptiles such as tortoise,
python, and water monitor lizards are exposed to heavy metals, tolerate high levels of radiation, feed on
rotten/germ-infested feed, thrive in unsanitary habitat and yet have prolonged lifespans. Such species are rarely
reported to develop cancer, suggesting the presence of anticancer molecules/mechanisms.
Methods:
Here, we tested effects from sera of Asian water monitor lizard (Varanus salvator), python (Malayopython
reticulatus) and tortoise (Cuora kamaroma amboinensis) against cancer cells. Sera were collected and
cytotoxicity assays were performed using prostate cancer cells (PC3), Henrietta Lacks cervical adenocarcinoma
cells (HeLa) and human breast adenocarcinoma cells (MCF7), as well as human keratinized skin cells (Hacat),
by measuring lactate dehydrogenase release as an indicator for cell death. Growth inhibition assays were performed
to determine the effects on cancer cell proliferation. Liquid chromatography mass spectrometry was
performed for molecular identification.
Results:
The findings revealed that reptilian sera, but not bovine serum, abolished viability of Hela, PC3 and
MCF7 cells. Samples were subjected to liquid chromatography mass spectrometry, which detected 57 molecules
from V. salvator, 81 molecules from Malayopython reticulatus and 33 molecules from C. kamaroma amboinensis
and putatively identified 9 molecules from V. salvator, 20 molecules from Malayopython reticulatus and 9 molecules
from C. kamaroma amboinensis when matched against METLIN database. Based on peptide amino acid composition,
binary profile, dipeptide composition and pseudo-amino acid composition, 123 potential Anticancer
Peptides (ACPs) were identified from 883 peptides from V. salvator, 306 potential ACPs from 1074 peptides
from Malayopython reticulatus and 235 potential ACPs from 885 peptides from C. kamaroma amboinensis.
Conclusion:
To our knowledge, for the first time, we reported comprehensive analyses of selected reptiles’ sera
using liquid chromatography mass spectrometry, leading to the identification of potentially novel anticancer
agents. We hope that the discovery of molecules from these animals will pave the way for the rational development
of new anticancer agents.
Homing: a case-study on the spatial memory of the Asian water monitor lizard Varanus salvator in the Kinabatangan floodplain