The Implication of Chemotypic Variation on the Anti-Oxidant and Anti-Cancer Activities of Sutherlandia frutescens (L.) R.Br. (Fabaceae) from Different Geographic Locations

Abstract

Extracts of Sutherlandia frutescens (cancer bush) exhibit considerable qualitative and quantitative chemical variability depending on their natural wild origins. The purpose of this study was thus to determine bioactivity of extracts from different regions using in vitro antioxidant and anti-cancer assays. Extracts of the species are complex and are predominantly composed of a species-specific set of triterpene saponins (cycloartanol glycosides), the sutherlandiosides, and flavonoids (quercetin and kaempferol glycosides), the sutherlandins. For the Folin-Ciocalteu phenolics test values of 93.311 to 125.330 mg GAE/g DE were obtained. The flavonoids ranged from 54.831 to 66.073 mg CE/g DE using the aluminum chloride assay. Extracts from different sites were also assayed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH•) radical scavenging method and ferric reducing anti-oxidant power (FRAP) methods. This was followed by an in vitro Cell Titer-Glo viability assay of various ecotypes using the DLD-1 colon cancer cell line. All test extracts displayed anti-oxidant activity through the DPPH• radical scavenging mechanism, with IC50 values ranging from 3.171 to 7.707 µg·mL−1. However, the degree of anti-oxidant effects differed on a chemotypic basis with coastal plants from Gansbaai and Pearly Beach (Western Cape) exhibiting superior activity whereas the Victoria West inland group from the Northern Cape, consistently showed the weakest anti-oxidant activity for both the DPPH• and FRAP methods. All extracts showed cytotoxicity on DLD-1 colon cancer cells at the test concentration of 200 µg·mL−1 but Sutherlandia plants from Colesburg (Northern Cape) exhibited the highest anti-cancer activity. These findings confirm that S. frutescens specimens display variability in their bioactive capacities based on their natural location, illustrating the importance of choosing relevant ecotypes for medicinal purposes.

In Vitro Cytotoxic Activity of African Plants: A Review

“…Other studies revealed IC 50 values higher than 100 µg/mL. For example, in the study of Zoyane et al (2020) [ 15 ] with S. frutescens extracts produced from plants growing at different geographic localities in South Africa, IC 50 values confirmed the relatively higher potency of plants from Colesburg, Zastron, and Gansbaai 1 (158.7, 172.7, and 176.7 µg/mL, respectively) [ 15 ]. Furthermore, in the study of Izuegbuna et al (2019) [ 17 ], the acetone-dried extract of O. stricta showed mild cytotoxicity (IC 50 = 110.1 µg/mL), and Unuofin et al (2018) [ 18 ] showed IC 50 values for aqueous and ethanol extracts of K. africana > 200 µg/mL.…”

“…Different assays were performed to evaluate the cytotoxicity effects of the studied African plant extracts, including a crystal violet cell antiproliferation assay [ 29 ], resazurin reduction assay [ 20 , 21 , 22 , 25 , 34 ], or tetrazolium-based colorimetric cell proliferation assays such as MTT [ 14 , 16 , 17 , 19 , 23 , 26 , 28 , 29 , 30 , 31 , 33 ], MTS [ 32 ] and WST-1 [ 13 ]. There were studies where cell numbers were determined using Hoechst 33342/Propidium Iodide (PI) staining [ 12 , 18 ], trypan blue [ 24 ], or were based on the quantification of Adenosin Triphosphate (ATP), signaling the presence of metabolically active cells [ 15 , 27 ].…”

“…The diverse biological properties of plant extracts can also be due to its chemical composition variability. Regarding the studies performed with plants from South Africa, for Zonyane et al (2020) [ 15 ], it is clear that anticancer activity shown for extracts of S. frutescensare is not necessarily strongly correlated to the flavonoids. Some other important chemicals found in that extract include sutherlandins isomers, triterpenoids, and cycloartenol glycosides (sutherlandiosides) [ 15 ].…”

“…Regarding the studies performed with plants from South Africa, for Zonyane et al (2020) [ 15 ], it is clear that anticancer activity shown for extracts of S. frutescensare is not necessarily strongly correlated to the flavonoids. Some other important chemicals found in that extract include sutherlandins isomers, triterpenoids, and cycloartenol glycosides (sutherlandiosides) [ 15 ]. In the study performed by Izuegbuna et al (2019), polyphenols (phenols, flavonoids, flavonols, proanthocyanidins, tannins) were the major compounds found in the several O. stricta extracts.…”

Anticancer Potential of Sutherlandia frutescens and Xysmalobium undulatum in LS180 Colorectal Cancer Mini-Tumors

“…Although a previous study in Caco-2 cells cultured in 2D demonstrated induction of apoptosis following treatment for 48 h, but the study used an ethanolic extract [ 30 ]. Cytotoxicity of S. frutescence was also confirmed in DLD-1 colon cancer cells cultured in 2D, with IC 50 values between 150 and 180 µg·mL −1 [ 31 ]. Furthermore, unlike paclitaxel, treatment with S. frutescens does not appear to induce gene expression of the CYP3A4 and CYP2D6 enzymes but rather maybe inhibits expression.…”