Solamargine, a bioactive steroidal alkaloid isolated from Solanum aculeastrum induces non-selective cytotoxicity and P-glycoprotein inhibition
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 extr...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-05-01
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| Series: | BMC Complementary and Alternative Medicine |
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| Online Access: | http://link.springer.com/article/10.1186/s12906-018-2208-7 |
| _version_ | 1819277678658715648 |
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| author | Trevor Burger Tsholofelo Mokoka Gerda Fouché Paul Steenkamp Vanessa Steenkamp Werner Cordier |
| author_facet | Trevor Burger Tsholofelo Mokoka Gerda Fouché Paul Steenkamp Vanessa Steenkamp Werner Cordier |
| author_sort | Trevor Burger |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-23T23:59:56Z |
| format | Article |
| id | doaj.art-ffd8662493d1443b8a5bb34ffabbb212 |
| institution | Directory Open Access Journal |
| issn | 1472-6882 |
| language | English |
| last_indexed | 2024-12-23T23:59:56Z |
| publishDate | 2018-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Complementary and Alternative Medicine |
| spelling | doaj.art-ffd8662493d1443b8a5bb34ffabbb2122022-12-21T17:25:09ZengBMCBMC Complementary and Alternative Medicine1472-68822018-05-0118111110.1186/s12906-018-2208-7Solamargine, a bioactive steroidal alkaloid isolated from Solanum aculeastrum induces non-selective cytotoxicity and P-glycoprotein inhibitionTrevor Burger0Tsholofelo Mokoka1Gerda Fouché2Paul Steenkamp3Vanessa Steenkamp4Werner Cordier5Department of Pharmacology, School of Medicine, Faculty of Health Sciences, University of PretoriaBiosciences Division, Council of Scientific and Industrial ResearchBiosciences Division, Council of Scientific and Industrial ResearchBiosciences Division, Council of Scientific and Industrial ResearchDepartment of Pharmacology, School of Medicine, Faculty of Health Sciences, University of PretoriaDepartment of Pharmacology, School of Medicine, Faculty of Health Sciences, University of PretoriaAbstract 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.http://link.springer.com/article/10.1186/s12906-018-2208-7CancerP-glycoproteinSolanum aculeastrumSolamargineSolasonineSteroidal alkaloids |
| spellingShingle | Trevor Burger Tsholofelo Mokoka Gerda Fouché Paul Steenkamp Vanessa Steenkamp Werner Cordier Solamargine, a bioactive steroidal alkaloid isolated from Solanum aculeastrum induces non-selective cytotoxicity and P-glycoprotein inhibition BMC Complementary and Alternative Medicine Cancer P-glycoprotein Solanum aculeastrum Solamargine Solasonine Steroidal alkaloids |
| title | Solamargine, a bioactive steroidal alkaloid isolated from Solanum aculeastrum induces non-selective cytotoxicity and P-glycoprotein inhibition |
| title_full | Solamargine, a bioactive steroidal alkaloid isolated from Solanum aculeastrum induces non-selective cytotoxicity and P-glycoprotein inhibition |
| title_fullStr | Solamargine, a bioactive steroidal alkaloid isolated from Solanum aculeastrum induces non-selective cytotoxicity and P-glycoprotein inhibition |
| title_full_unstemmed | Solamargine, a bioactive steroidal alkaloid isolated from Solanum aculeastrum induces non-selective cytotoxicity and P-glycoprotein inhibition |
| title_short | Solamargine, a bioactive steroidal alkaloid isolated from Solanum aculeastrum induces non-selective cytotoxicity and P-glycoprotein inhibition |
| title_sort | solamargine a bioactive steroidal alkaloid isolated from solanum aculeastrum induces non selective cytotoxicity and p glycoprotein inhibition |
| topic | Cancer P-glycoprotein Solanum aculeastrum Solamargine Solasonine Steroidal alkaloids |
| url | http://link.springer.com/article/10.1186/s12906-018-2208-7 |
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