Gut microbes of animals living in polluted environments are potential source of novel anticancer agents
One of the leading causes of mortality and morbidity worldwide, cancer is a major medical concern with 18.1 and 9.6 million new cancer cases and deaths respectively recorded in 2018 based on statistics from the International Agency for Research on Cancer. The number of deaths related to cancer is st...
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| Format: | Thesis |
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2020
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| Online Access: | http://eprints.sunway.edu.my/2429/ |
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| Summary: | One of the leading causes of mortality and morbidity worldwide, cancer is a major medical concern with 18.1 and 9.6 million new cancer cases and deaths respectively recorded in 2018 based on statistics from the International Agency for Research on Cancer. The number of deaths related to cancer is still on the rise, despite the various treatment options available. Thus, there is an urgent need for the development of novel anticancer agents. Previous work has shown that animals such as crocodiles that, thrive in polluted environments, and still benefit from prolonged lifespan, may possess mechanisms shielding them from cancer. This could be due to their immune system, or their gut microbiota. Various previous work has shown that the host benefits from their gut microbiota. Here we assessed the gut bacteria of various animals ranging from vertebrates to invertebrates procured from their natural habitat, for their potential anticancer effects. The gut bacteria of the selected animals were isolated, identified and subjected to conditioned media preparation. The anticancer potential of the prepared conditioned media were assessed through 4 assays, namely: growth inhibition, MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cell viability, lactate dehydrogenase cytotoxicity and cell survival assays using a panel of cell lines: Henrietta Lacks cervical adenocarcinoma cells, human breast adenocarcinoma cells, human prostate cancer cells, and normal human skin cells. Furthermore, liquid chromatography-mass spectrometry was employed to identify the molecules present. A plethora of bacteria were isolated from the gut of dissected animals. Moreover, conditioned media prepared from gut bacteria of the crocodile, water monitor lizard, python, bullfrog, pigeon, tilapia, tarantula, and scorpion exhibited anticancer activity. Selected conditioned media exhibited apoptosis-like effect in cells. Of note, the results indicated the presence of several molecules with previously reported antitumour activity, namely: Butylidene-7-hydroxyphthalide, C75, Dihydroxymelphalan, Enigmol, Estrone 16-oxime, Gingerol, L,L-Cyclo(leucylprolyl), PD 98059, Proglumide, S-Allyl-L-cysteine and U-0126. Furthermore, several hundred potentially novel molecules from vertebrates and invertebrates respectively, were depicted, which are of great interest for future research. Thus, the gut microbiota of selected animals can be considered as a great niche of antitumour molecules, however further in vitro and in vivo studies are needed to realise these expectations. |
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