期刊
PHYTOCHEMISTRY
卷 203, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.phytochem.2022.113354
关键词
Momordica balsamina; Cucurbitaceae; African pumpkin; Cucurbitane-type triterpenoids; Multidrug resistance; P-glycoprotein
资金
- Fundacao para a Ciencia e a Tecnologia (FCT) , Portugal [PTDC/MED-QUI/30591/2017]
- Bilateral Portuguese-Hungarian Science & Technology Cooperation (FCT/NKFIH) [2019/2020]
- Szeged Foundation for Cancer Research
- National NMR Network (PTNMR) [022161]
- FEDER through COMPETE
- FCT through PIDDAC [REDE/1501/REM/2005]
Compounds extracted from Momordica balsamina have shown potential as multidrug resistance (MDR) reversers and have synergistic effects with doxorubicin.
Aiming at overcoming multidrug resistance (MDR) in cancer, we have been studying Momordica balsamina, a vegetable known as African pumpkin. Five undescribed cucurbitane-type triterpenoids (balsaminaepoxide, bal-saminatriol, balsaminoic acid, balsaminal, and balsaminol G) along with five known cucurbitacins were isolated from the methanol extract of Momordica balsamina aerial parts, whose structures were elucidated by spectro-scopic data, mainly 1D and 2D NMR experiments. Compounds were evaluated for their ability as P-glycoprotein (P-gp/ABCB1) inhibitors in multidrug resistant human ABCB1-transfected mouse lymphoma cells (L5178Y, MDR) and resistant human colon adenocarcinoma cells (COLO 320), using the rhodamine-123 exclusion test, by flow cytometry. Several compounds, which were found to be non-cytotoxic, strongly inhibited P-gp efflux ac-tivity in a dose-dependent manner in both cell models. In MRD mouse lymphoma cells, balsaminol G and kar-avilagenin B were the most active, while in resistant colon adenocarcinoma cells, the strongest inhibitory activity was found for balsaminaepoxide, balsaminatriol and karavilagenin C, being several-fold more active than the positive control verapamil. In chemosensitivity assays, in a model of combination chemotherapy, selected compounds showed to interact synergistically with doxorubicin, thus substantiating their potential as MDR re-versers. The strongest synergistic interaction was found for balsaminal and balsaminol G.
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