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Decrease of ABCB1 protein expression and increase of G1 phase arrest induced by oleanolic acid in human
Didi Wang1, Jincai Wang2, Juan Zhang2
1Key Laboratory of Microecology-immune Regulatory Network and Related Diseases, School of Basic Medicine, Jiamusi University, Jiamusi, Heilongjiang 154000, P.R. China.
Experimental and Therapeutic Medicine
|May 31, 2021
Summary
Oleanolic acid (OA) enhances sensitivity in multidrug-resistant cancer cells by reducing ABCB1 expression and inducing G1 phase arrest. This natural compound shows potential for cancer therapy by overcoming drug resistance.
Area of Science:
- Natural Product Chemistry
- Cancer Biology
- Pharmacology
Background:
- Oleanolic acid (OA) is a plant-derived compound with diverse biological activities.
- The precise mechanism of OA action in human tumor cells, particularly in overcoming drug resistance, is not fully understood.
- Caveolin-1 overexpression was previously linked to OA sensitivity in leukemia cells.
Purpose of the Study:
- To investigate the effects of Oleanolic acid (OA) on drug-resistant human breast cancer (MCF-7/DOX) and leukemia (HL-60/HAR) cell lines.
- To evaluate the role of caveolin-1 in OA sensitivity in resistant breast cancer cells.
- To determine the impact of OA on cell cycle progression, apoptosis, and drug resistance mechanisms, specifically ABCB1 expression.
Main Methods:
- Cell viability assays (CCK-8) to assess drug sensitivity.
- Western blotting to measure protein expression levels.
- Flow cytometry for cell cycle analysis and apoptosis assays (Annexin V/PI staining).
- Rhodamine 123 accumulation assay to evaluate ABCB1 substrate activity.
Main Results:
- Oleanolic acid (OA) demonstrated increased sensitivity in harringtonine-resistant HL-60/HAR cells compared to parental HL-60 cells.
- Doxorubicin-resistant MCF-7/DOX cells showed similar OA susceptibility regardless of caveolin-1 expression levels.
- OA treatment induced G1 phase arrest in both resistant cell lines and promoted apoptosis, although not through classical caspase-3/PARP-1 cleavage.
- OA treatment decreased ATP-binding cassette subfamily B member 1 (ABCB1) protein expression in a concentration-dependent manner in resistant cells and was not an ABCB1 substrate.
Conclusions:
- Oleanolic acid (OA) exhibits potential in combating multidrug resistance in cancer cells.
- OA's efficacy may stem from its ability to downregulate ABCB1 protein expression and induce G1 cell cycle arrest.
- Further research into OA as a therapeutic agent for resistant cancers is warranted.
Keywords:
ATP-binding cassette subfamily B member 1caveolin-1cell cyclemultidrug resistance in tumoroleanolic acidMore Related Videos
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