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A natural product, voacamine, sensitizes paclitaxel-resistant human ovarian cancer cells.
Pellegrini, Evelin; Multari, Giuseppina; Gallo, Francesca Romana; Vecchiotti, Davide; Zazzeroni, Francesca; Condello, Maria; Meschini, Stefania.
Afiliación
  • Pellegrini E; National Center for Drug Research and Evaluation, National Institute of Health, 00161 Rome, Italy.
  • Multari G; National Center for Drug Research and Evaluation, National Institute of Health, 00161 Rome, Italy.
  • Gallo FR; National Center for Drug Research and Evaluation, National Institute of Health, 00161 Rome, Italy.
  • Vecchiotti D; Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, 67100 L'Aquila, Italy.
  • Zazzeroni F; Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, 67100 L'Aquila, Italy.
  • Condello M; National Center for Drug Research and Evaluation, National Institute of Health, 00161 Rome, Italy.. Electronic address: maria.condello@iss.it.
  • Meschini S; National Center for Drug Research and Evaluation, National Institute of Health, 00161 Rome, Italy.. Electronic address: stefania.meschini@iss.it.
Toxicol Appl Pharmacol ; 434: 115816, 2022 01 01.
Article en En | MEDLINE | ID: mdl-34856211
Most women with ovarian cancer are treated with chemotherapy before or after surgery. Unfortunately, chemotherapy treatment can cause negative side effects and the onset of multidrug resistance (MDR). The aim of this study is to evaluate the chemosensitizing effect of a natural compound, voacamine (VOA), in ovarian (A2780 DX) and colon (LoVo DX) cancer drug-resistant cell lines which overexpress P-glycoprotein (P-gp), in combination with paclitaxel (PTX), or doxorubicin (DOX) or 5-fluorouracil (5-FU). VOA, a bisindole alkaloid extracted from Peschiera fuchsiaefolia, has already been shown to be effective in enhancing the effect of doxorubicin, because it interferes with the P-gp function. Ovarian cancer cytotoxicity test shows that single treatments with VOA, DOX and PTX do not modify cell viability, while pretreatment with VOA, and then PTX or DOX for 72 h, induces a decrease. In colon cancer, since 5-FU is not a-substrate for P-gp, VOA has no sensitizing effect while in VOA + DOX there is a decrease in viability. Annexin V/PI test, cell cycle analysis, activation of cleaved PARP1 confirm that VOA plus PTX induce apoptotic cell death. Confocal microscopy observations show the different localization of NF-kB after treatment with VOA + PTX, confirming the inhibition of nuclear translocation induced by VOA pretreatment. Our data show the specific effect of VOA which only works on drugs known to be substrates of P-gp.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Paclitaxel / Resistencia a Antineoplásicos / Ibogaína / Antineoplásicos Fitogénicos Límite: Female / Humans Idioma: En Revista: Toxicol Appl Pharmacol Año: 2022 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Paclitaxel / Resistencia a Antineoplásicos / Ibogaína / Antineoplásicos Fitogénicos Límite: Female / Humans Idioma: En Revista: Toxicol Appl Pharmacol Año: 2022 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos