Crocodylus porosus: a potential source of anticancer moleculesCrocodylus porosus: a potential source of anticancer molecules

Abstract

BackgroundCancer remains a global threat resulting in significant morbidity and mortality despite advances in therapeutic interventions, suggesting urgency for identification of anticancer agents. Crocodiles thrive in polluted habitat, feed on germ-infested meat, are exposed to carcinogenic heavy metals, are the very few species to survive the catastrophic Cretaceous–Paleogene extinction event, yet have a prolonged lifespan and rarely been reported to develop cancer. Therefore, we hypothesised that animals living in polluted environments such as crocodiles possess anticancer molecules/mechanisms.MethodsCrocodylus porosus was procured, blood collected, dissected and lysates prepared from internal organs. Organ lysates and sera were tested for growth inhibition, cytotoxic effects and cell survival against HeLa, PC3 and MCF7 cells and subjected to liquid chromatography mass spectrometry. RNA transcriptome analysis and differential gene analysis were performed using Galaxy Bioinformatics.ResultsSera exhibited potent growth inhibition and cytotoxic effects against cancer cells. 80 molecules were detected from C. porosus and 19 molecules were putatively identified. Additionally, more than 100 potential anticancer peptides were identified from sera using bioinformatics based on peptide amino acid composition, binary profile, dipeptide composition and pseudo-amino acid composition. Following transcriptome analysis, 14 genes in treated HeLa cells, 51 genes in treated MCF7 cells and 2 genes in treated PC3 cells, were found to be expressed, compared with untreated controls.ConclusionAnimals residing in polluted milieus are an unexploited source for prospective pharmaceutical drugs, and could lead to identification of novel antitumour compound(s) and/or further understanding of the mechanisms of cancer resistance.

Longevity, cellular senescence and the gut microbiome: lessons to be learned from crocodiles

“…Moreover, this study elucidated the differential gene analysis of cancer cells incubated with crocodile sera. These analyses revealed that 51 genes in breast cancer cells, 14 genes in treated cervical cancer cells and 2 genes in prostate cancer cell lines were differentially expressed in comparison to untreated cells and the study revealed that these genes were typically involved in cellular communication, DNA growth and repair, respiration and others ( Jeyamogan et al., 2020 ). Nonetheless, the precise genetic mechanisms for these anti-cancer effects remain to be determined, and further research to determine the connection with the gut microbiome and its’ metabolites are currently underway ( Khan et al., 2021 ).…”

“…This was based on the longevity of crocodiles, with some living up to 100 years and our visits to numerous crocodile farms and sanctuaries as well as personal communication with veterinarians and zoologists, who indicated the absence of cancer cases in these species ( Jeyamogan et al., 2017 ). In this regard a study was conducted, whereby the anti-cancer effects of crocodile sera and various organ lysates were investigated against cervical, breast and prostate cancer cells ( Jeyamogan et al., 2020 ). Crocodile serum depicted potent growth inhibitory effects as well as cytotoxic effects against the cancer cells investigated.…”

“…Moreover, 80 molecules were elucidated as well as 19 molecules were identified from the crocodile. In addition, approximately 100 potential anticancer peptides were recognized from crocodile serum via a bioinformatics approach centered on binary profile, dipeptide and peptide amino acid composition, and pseudo-amino acid composition ( Jeyamogan et al., 2020 ). Moreover, this study elucidated the differential gene analysis of cancer cells incubated with crocodile sera.…”

“…At present there is limited understanding of the crocodile gut microbiome and for reptiles in general, although preliminary studies have isolated and identified potentially innovative as well as some already known molecules from crocodile gut bacterial metabolites which depict inhibition of cell metabolic activity or viability reduction, and cell survival inhibition in cancerous cell lines ( Khan et al., 2021 ). Furthermore, crocodile serum portrays powerful growth inhibitory effects as well as cytotoxic effects against cancer cells, and several known and unknown molecules were identified from the crocodile sera, as well as and estimated 100 potential anticancer peptides being recognized ( Jeyamogan et al., 2020 ). Further work on the microbiome and its’ associated metabolites may lead to the recognition of potential innovative therapeutic leads for clinical and pre-clinical investigations in invertebrate and animal models of ageing and/or disease ( Figure 1 ).…”

“…Crocodiles are a remarkable species, being designated as “living fossils” and have been described as anachronism ( Meyer, 1984 ; Stockdale and Benton, 2021 ). They have been around for the last 85 million years, and survived mass extinction events, such as the catastrophic Cretaceous-Tertiary extinction event ( Tokaryk, 1991 ; Jeyamogan et al., 2020 ). In fact, ancestors of the crocodile have existed since the Early Jurassic period of around 200 Million years ago, and looked very similar to the modern crocodiles ( Tykoski et al., 2002 ; Stockdale and Benton, 2021 ).…”