Microalgal metabolites as anti-cancer/anti-oxidant agents reduce cytotoxicity of elevated silver nanoparticle levels against non-cancerous vero cells

Abstract

Heavy metal pollution has become a major concern globally as it contaminates eco-system, water networks and as finely suspended particles in air. In this study, the effects of elevated silver nanoparticle (AgNPs) levels as a model system of heavy metals, in the presence of microalgal crude extracts (MCEs) at different ratios, were evaluated against the non-cancerous Vero cells, and the cancerous MCF-7 and 4T1 cells. The MCEs were developed from water (W) and ethanol (ETH) as green solvents. The AgNPs-MCEs-W at the 4:1 and 5:1 ratios (v/v) after 48 and 72 h treatment, respectively, showed the IC 50 values of 83.17–95.49 and 70.79–91.20 μg/ml on Vero cells, 13.18–28.18 and 12.58–25.7 μg/ml on MCF-7; and 16.21–33.88 and 14.79–26.91 μg/ml on 4T1 cells. In comparison, the AgNPs-MCEs-ETH formulation achieved the IC 50 values of 56.23–89.12 and 63.09–91.2 μg/ml on Vero cells, 10.47–19.95 and 13.48–26.61 μg/ml on MCF-7; 14.12–50.11 and 15.13–58.88 μg/ml on 4T1 cells, respectively. After 48 and 72 h treatment, the AgNPs-MCE-CHL at the 4:1 and 5:1 ratios exhibited the IC 50 of 51.28–75.85 and 48.97–69.18 μg/ml on Vero cells, and higher cytotoxicity at 10.47–16.98 and 6.19–14.45 μg/ml against MCF-7 cells, and 15.84–31.62 and 12.58–24.54 μg/ml on 4T1 cells, respectively. The AgNPs-MCEs-W and ETH resulted in low apoptotic events in the Vero cells after 24 h, but very high early and late apoptotic events in the cancerous cells. The Liquid Chromatography-Mass Spectrometry-Electrospray Ionization (LC-MS-ESI) metabolite profiling of the MCEs exhibited 64 metabolites in negative ion and 56 metabolites in positive ion mode, belonging to different classes. The microalgal metabolites, principally the anti-oxidative components, could have reduced the toxicity of the AgNPs against Vero cells, whilst retaining the cytotoxicity against the cancerous cells.

Cytotoxicity and 1H NMR metabolomics analyses of microalgal extracts for synergistic application with Tamoxifen on breast cancer cells with reduced toxicity against Vero cells

“…However, they still have an α or β interferon receptor, such that they respond normally when complex interferon is added to the culture media ( Desmyter et al., 1968 ). Our work proved that the presence of MCEs reduced the cytotoxicity of TMX or AgNPs against the Vero cells, whilst at the same time the TMX or AgNPs-MCEs synergistic formulations improved the cytotoxicity of MCEs on MCF-7 and 4T1 cells ( Hussein et al., 2020a , b , d ). This should be of great interest in cancer therapeutics as the cytotoxicity of TMX on the normal cells has been widely reported ( Salih et al., 2017 ; Yusmazura et al., 2017 ).…”

“…The new chemo-preventive drugs against breast cancer need to consider the safety and efficacy aspects to improve the therapeutics management and reduce the high cost and pain of patients ( Steward and Brown, 2013 ). There has been an increasing interest to develop novel therapeutic strategies against cancer using drugs or cytotoxic agents based on natural compounds ( Gurunathan et al., 2013 ; Hussein et al., 2020a , b , c , d ). Natural-based products including benzylpenicillin, didemnin B, girolline, lovastatin, bryostatin 1, dolastatin 10, cryptophycins, kahalalide F and bengamide derivative are utilized in clinical trials for cancer, cognitive diseases, analgesia and allergy ( Newman and Cragg, 2004 ).…”

“…The microalgal bioactive compounds are also effective against many pathogens ( El-hack et al., 2019 ). The co-applications of microalgal metabolites with silver nanoparticles have been proven to enhance cytotoxic effects against breast cancer cells, but with reduced toxicity against the non-cancerous Vero cells ( Hussein et al., 2020a , b , d ). Combination therapy has shown good potential in the treatment of cancer where the cytotoxicity and therapeutic activity can be increased by utilizing multiple drugs with various mechanisms of action delivered to the same disease site ( Gao et al., 2015 ).…”

Genetic Engineering of Microalgae for Secondary Metabolite Production: Recent Developments, Challenges, and Future Prospects

“…Silver Nanoparticles are commonly employed in cancer treatment to induce cytotoxicity in cancer cells, but non-cancer cells are frequently damaged as well. To lessen such negative effects of nanoparticle application, combination of metabolites from microalgal crude extract could benefit theranostics ( Hussein et al, 2020 ) by limiting the damage to non-cancerous cells. Microalgal crude extracts can be made with a variety of solvents, including water, ethanol, diethylether, and others, to study their antibacterial and anticancer properties.…”

Recent Progress in Microalgal Squalene Production and Its Cosmetic Application

“…In these assays, first step is cultivation of the selected animal cell culture to obtain enough amount of them for analyzation. At this point, cell lines named Vero, 4T1, MCF-7, MCF-10A, MDA-MB-231, HepG2 or B16F10 can be used [79][80][81][82]. After that, the cell culture is treated with different concentration of squalene and incubated.…”