Abstract |
The collateral sensitivity effect is among the most promising strategies for overcoming multidrug resistance in cancer. In this work, 28 cucurbitane-type triterpenoids (1: -28: ), previously isolated from the African medicinal plant Momordica balsamina and its derivatives, were evaluated for their collateral sensitivity effect on three different human cancer entities, gastric (EPG85-257), pancreatic (EPP85-181), and colon (HT-29), each with two different multidrug-resistant variants. One was selected for its resistance to daunorubicin (EPG85-257RDB, EPP85-181RDB, HT-29RDB) and the other was selected for its resistance to mitoxantrone (EPG85-257RNOV, EPP85-181RNOV, HT-29RNOV). On gastric cell lines, the best results were obtained for compounds 3: and 10: , which exhibited a collateral sensitivity effect together with high antiproliferative activity. In turn, on colon cancer cell lines, the best multidrug resistance-selective antiproliferative effects were observed for derivatives 11, 13: , and 15: , which showed collateral sensitivity effects against both resistant variants. Compounds 11: and 3: were also the most selective against the multidrug resistance pancreatic cells lines. Some compounds, such 6, 10, 11: and 15: , were previously found to be strong P-glycoprotein modulators, thus highlighting their potential as promising leads for overcoming multidrug resistance in cancer cells.
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Authors | Cátia Ramalhete, Silva Mulhovo, Hermann Lage, Maria-José U Ferreira |
Journal | Planta medica
(Planta Med)
Vol. 84
Issue 18
Pg. 1372-1379
(Dec 2018)
ISSN: 1439-0221 [Electronic] Germany |
PMID | 29996165
(Publication Type: Journal Article)
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Copyright | Georg Thieme Verlag KG Stuttgart · New York. |
Chemical References |
- Antineoplastic Agents, Phytogenic
- Triterpenes
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Topics |
- Antineoplastic Agents, Phytogenic
(chemistry, pharmacology)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Drug Resistance, Multiple
(drug effects)
- Drug Resistance, Neoplasm
(drug effects)
- Drug Screening Assays, Antitumor
- Humans
- Inhibitory Concentration 50
- Momordica
(chemistry)
- Plant Components, Aerial
(chemistry)
- Triterpenes
(chemistry, pharmacology)
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