A natural product, voacamine, sensitizes paclitaxel-resistant human ovarian cancer cells
Autor: | Francesca Romana Gallo, Maria Condello, Evelin Pellegrini, Stefania Meschini, Francesca Zazzeroni, Davide Vecchiotti, Giuseppina Multari |
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Rok vydání: | 2021 |
Předmět: |
Paclitaxel
Cell Survival medicine.medical_treatment Multidrug resistance Carcinoma Ovarian Epithelial Toxicology chemistry.chemical_compound Annexin P-gp substrate drugs Cell Line Tumor medicine Humans Doxorubicin Viability assay ATP Binding Cassette Transporter Subfamily B Member 1 Ovarian cancer cells Pharmacology Ovarian Neoplasms Chemotherapy Molecular Structure Chemistry Cancer medicine.disease Antineoplastic Agents Phytogenic Gene Expression Regulation Neoplastic Cell culture Drug Resistance Neoplasm Voacamine Ibogaine Colonic Neoplasms Cancer research Female Ovarian cancer medicine.drug |
Zdroj: | Toxicology and applied pharmacology. 434 |
ISSN: | 1096-0333 |
Popis: | 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. |
Databáze: | OpenAIRE |
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