Voacamine: Alkaloid with its essential dimeric units to reverse tumor multidrug resistance.
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| Abstract |
Search for natural substances in association with conventional chemotherapeutic drugs with a chemiosensitizing action easily accessible to the tumor mass has encouraged our studies on voacamine (VOA) and its monomeric units, voacangine and vobasine. Our previous results showed that VOA sensitized multidrug resistant (MDR) osteosarcoma cells (U-2 OS/DX) to doxorubicin (DOX) cytotoxicity. VOA, extracted by Peschiera fuchsiaefolia plant, is a bisindole alkaloid consisting of an Iboga skeleton (voacangine) directly linked to a 2-acyl indole unit (vobasine). High-performance thin-layer chromatography densitometry demonstrated the purity of VOA, voacangine and vobasine samples. Flow cytometry analysis showed that VOA, voacangine and vobasine enhanced DOX accumulation of U-2 OS/DX cells, in equally way, whereas VOA reduced more efficiently DOX efflux. Optical microscopy and clonogenic assay confirmed that VOA was more effective than voacangine and vobasine in enhancing DOX cytotoxic effect. These results showed that monomers linked together are necessary to modulate resistant phenotype of osteosarcoma cells. To complete the study, we evaluated the effect of three compounds on microtubules by confocal microscopy, suggesting that only the whole molecule depolymerizes the microtubules blocking so DOX efflux-mediated by vesicles.
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| Authors | Maria Condello, Evelin Pellegrini, Giuseppina Multari, Francesca Romana Gallo, Stefania Meschini |
| Journal | Toxicology in vitro : an international journal published in association with BIBRA (Toxicol In Vitro) Vol. 65 Pg. 104819 (Jun 2020) ISSN: 1879-3177 [Electronic] England |
| PMID | 32135239 (Publication Type: Journal Article) |
| Copyright | Copyright © 2020 Elsevier Ltd. All rights reserved. |
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