BackgroundPrevious reports showed that the Steroidal Glycoalkaloid Solamargine inhibited proliferation of non-melanoma skin cancer cells. However, Solamargine was not tested systematically on different types of melanoma cells and was not simultaneously tested on normal cells either. In this study we aimed to investigate the effect of Solamargine and the mechanism involved in inhibiting the growth of different types of melanoma cells.MethodsSolamargine effect was tested on normal cells and on another three melanoma cell lines. Vertical growth phase metastatic and primary melanoma cell lines WM239 and WM115, respectively and the radial growth phase benign melanoma cells WM35 were used. The half inhibitory concentration IC50 of Solamargine was determined using Alamarblue assay. The cellular and subcellular changes were assessed using light and Transmission Electron Microscope, respectively. The percentage of cells undergoing apoptosis and necrosis were measured using Flow cytometry. The different protein expression was detected and measured using western blotting. The efficacy of Solamargine was determined by performing the clonogenic assay. The data collected was analyzed statistically on the means of the triplicate of at least three independent repeated experiments using one-way ANOVA test for parametric data and Kruskal–Wallis for non-parametric data. Differences were considered significant when the P values were less than 0.05.ResultsHereby, we demonstrate that Solamargine rapidly, selectively and effectively inhibited the growth of metastatic and primary melanoma cells WM239 and WM115 respectively, with minimum effect on normal and benign WM35 cells. Solamargine caused cellular necrosis to the two malignant melanoma cell lines (WM115, WM239), by rapid induction of lysosomal membrane permeabilization as confirmed by cathepsin B upregulation which triggered the extrinsic mitochondrial death pathway represented by the release of cytochrome c and upregulation of TNFR1. Solamargine disrupted the intrinsic apoptosis pathway as revealed by the down regulation of hILP/XIAP, resulting in caspase-3 cleavage, upregulation of Bcl-xL, and Bcl2, and down regulation of Apaf-1 and Bax in WM115 and WM239 cells only. Solamargine showed high efficacy in vitro particularly against the vertical growth phase melanoma cells.ConclusionOur findings suggest that Solamargine is a promising anti-malignant melanoma drug which warrants further attention.Electronic supplementary materialThe online version of this article (doi:10.1186/s12935-016-0287-4) contains supplementary material, which is available to authorized users.
Please cite this article in press as: S.S. Al Sinani, et al. Variations in the cytotoxic glycoalkaloids solamargine and solasonine in different parts of the Solanum incanum plant during its growth and development in Oman, J. Taibah Univ. Sci. (2015), http://dx. AbstractIn addition to several important traditional medicine applications of Solanum incanum, the plant is a rich source of important cytotoxic glycoalkaloids, such as solamargine and solasonine. Because S. incanum is a potential source of compounds for steroid synthesis, it is worthwhile to study the content of these important glycoalkaloids during plant developmental stages. Therefore, an attempt has been made to quantitatively estimate solasonine and solamargine content using an optimized isolation process and a newly developed and validated HPTLC method using different parts of S. incanum plants at different developmental stages and comparing changes in the whole-plant GAs profile during the growth and development of S. incanum plants in Oman. Solamargine and solasonine produced well-separated compact bands with R f values of 0.26 and 0.14, respectively, on silica gel HPTLC plates using chloroform:methanol:5% ammonia (7:3:0.5, v/v/v) after visualization using anisaldehyde sulphuric acid reagent. The chromatograms were scanned at 530 nm wavelength and the simultaneous method was linear (r 2 ≥ 0.9962) in concentrations ranging from 50 to 2000 ng/spot for both of the drugs. The validated method was applied to analyse solamargine and solasonine in small, young, immature and mature leaves as well as stem and root parts up to the 40th week of plants' growth, and showed a rich concentration of glycoalkaloids with large variations at different stages of plant development. Hence, this study highlights the importance of developmental stages of particular organs and the overall age of the plant when harvesting for these GAs from S. incanum plants.
In addition to its traditional medicinal importance, Solanum incanum (thorn apple) is also a rich source of important cytotoxic glycoalkaloids such as solamargine and solasonine. The effect of salinity stress on solamargine and solasonine production by Solanum incanum plants grown in soil has been investigated. Salinity stress has been applied by adding NaCl to the soil, in concentrations: 0.0 (control), 75, 150, and 225 mM for 8 weeks. HPTLC method was used for analysis of solamargine and solasonine in leaves, stem and roots. A positive correlation was observed between 150 mM NaCl salinity and production of solamargine and solasonine in leaves. In roots, solamargine content was not affected by NaCl treatment, whereas solasonine content increased with a short-term salinity treatment. However, salinity seems to reduce the production of solamargine and solasonine in the roots of Solanum incanum. The possibility of using NaCl as an efficient and economical elicitor of glycoalkaloid production in Solanum incanum plants is rejected on the basis of the results obtained.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.