Abstract
Background: Solanum aculeastrum fruits are used by some cancer sufferers as a form of alternative treatment.
Scientific literature is scarce concerning its anticancer activity, and thus the aim of the study was to assess the in
vitro anticancer and P-glycoprotein inhibitory potential of extracts of S. aculeastrum fruits. Furthermore, assessment
of the combinational effect with doxorubicin was also done.
Methods: The crude extract was prepared by ultrasonic maceration. Liquid-liquid extraction yielded one aqueous
and two organic fractions. Bioactive constituents were isolated from the aqueous fraction by means of column
chromatography, solid phase extraction and preparative thin-layer chromatography. Confirmation of bioactive
constituent identity was done by nuclear magnetic resonance and ultra-performance liquid chromatography mass
spectrometry. The crude extract and fractions were assessed for cytotoxicity and P-glycoprotein inhibition in both
cancerous and non-cancerous cell lines using the sulforhodamine B and rhodamine-123 assays, respectively.
Results: Both the crude extract and aqueous fraction was cytotoxic to all cell lines, with the SH-SY5Y
neuroblastoma cell line being most susceptible to exposure (IC50 = 10.72 μg/mL [crude], 17.21 μg/mL [aqueous]).
Dose-dependent P-glycoprotein inhibition was observed for the crude extract (5.9 to 18.9-fold at 100 μg/mL) and
aqueous fraction (2.9 to 21.2 at 100 μg/mL). The steroidal alkaloids solamargine and solanine were identified. While
solanine was not bioactive, solamargine displayed an IC50 of 15.62 μg/mL, and 9.1-fold P-glycoprotein inhibition at
100 μg/mL against the SH-SY5Y cell line. Additive effects were noted for combinations of doxorubicin against the
SH-SY5Y cell line.
Conclusions: The crude extract and aqueous fraction displayed potent non-selective cytotoxicity and noteworthy
P-glycoprotein inhibition. These effects were attributed to solamargine. P-glycoprotein inhibitory activity was only
present at concentrations higher than those inducing cytotoxicity, and thus does not appear to be the likely
mechanism for the enhancement of doxorubicin’s cytotoxicity. Preliminary results suggest that non-selective
cytotoxicity may hinder drug development, however, further assessment of the mode of cell death is necessary to
determine the route forward.