Abstract
Medicinal plants indicated for chronic diseases usually have good safety margins as they are intended for lifelong treatments. We hypothesized that they may provide patients with baseline protection to cancers and multidrug resistance-reversing phytochemicals resulting in successful prevention and/or adjuvant treatment of chemotherapy-resistant cancers. We selected 27 popular herbal infusions widely used in Nigeria for diabetes and studied their effects on a panel of liver (HepG2), colon (Caco2), and skin (B16-F10) cancer cells. Cytotoxicity was measured using the SRB staining assay. The 2D antimigratory effect was evaluated using an Oris™ platform. The P-glycoprotein (P-gp) efflux activity was evaluated using Rh-123 as a fluorescent probe. The inhibition of tyrosinase-mediated melanogenesis was evaluated by colorimetric enzymatic assays. Our results show that melanoma cell proliferation was strongly inhibited by Anogeissus leiocarpus (Combretaceae), Bridelia ferruginea (Phyllanthaceae), D. ogea (Leguminosae), and Syzygium guineense (Myrtaceae) extracts (GI50 = 50 µg/ml). Alstonia boonei (Apocynaceae), Gongronema latifolium (Asclepiadaceae), and Strophanthus hispidus (Apocynaceae) were preferentially toxic against Caco2 (GI50 = 50, 5 and 35 µg/ml, respectively). The most active extracts against different drug resistance mechanisms were B. ferruginea (inhibition of P-gp efflux, and impairing tyrosinase activity) and X. americana (inhibition of P-gp efflux). A. leiocarpus, Kaya senegalensis (Meliaceae), S. guineense, and Terminalia avicennioides (Combretaceae) significantly inhibited B16-F10 cell migration. Lupeol, ursolic acid, quercitrin, epicatechin, gallic acid, and ellagic acid were dereplicated by HPLC and HPTLC as their bioactive phytochemicals. In conclusion, the above in-vitro activities of herbal infusions regularly consumed by Nigerian diabetic patients may either act as a baseline chemoprotection or as sensitizing agents.
Highlights
Natural products are both the base of traditional medicine and important sources of lead molecules in drug discovery (Thomford et al, 2018)
In line with the topic of this special issue, we studied the cytotoxicity of the aqueous plant extracts toward a panel of liver (HepG2), colon (Caco2) and skin (B16-F10) cancer cells as well as their effects upon selected mechanisms of drug resistance in cancer cells, namely, the efflux of xenobiotics by Pgp (Ozben, 2006), and the ability to inhibit tyrosinase-mediated melanogenesis and melanoma migration capacity (Pinon et al, 2011)
Rather than calculating exact values, we classified the Growth Inhibition 50% (GI50) between standard doses and applied the threshold proposed by Suffness and Pezzuto (1999), which establishes that crude extracts showing an GI50 ≤ 100 μg/ml can be considered to be cytotoxic and selected for further studies, whereas the most promising ones are those with an GI50 lower than 30 μg/ml
Summary
Natural products are both the base of traditional medicine and important sources of lead molecules in drug discovery (Thomford et al, 2018). It is known that many herbal extracts (traditional medicines) act as chemosensitizers or resistance modulators (Tinoush et al, 2020). A key aspect of their activity is their ability to modulate multiple survival pathways with very low toxicity (Aung et al, 2017). The choice of synthetic drugs against MDR is very limited (Dallavalle et al, 2020). The search for new natural product addressing this gap offers potential new avenues. Our research groups is actively screening and testing for candidates from natural sources that can modulate the function, or expression, of disease-linked ABC transporters (Syed and Coumar, 2016)
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