Biological Activity of Oleanolic Acid Derivatives HIMOXOL and Br-HIMOLID in Breast Cancer Cells Is Mediated by ER and EGFR
Abstract
:1. Introduction
2. Results
2.1. Optimization of Receptor Blocker Concentration
2.2. Contribution of ER and EGFR to the Response of MCF7 and MDA-MB-231 Cells to OA or Its Derivatives
2.3. Contribution of ER and EGFR to the Genotoxic Effect of OA or Its Derivatives in MCF7 and MDA-MB-231 Cells
2.4. Contribution of ER and EGFR to the Cell Cycle Distribution in MCF7/ER+/− and MDA-MB-231/EGFR+/− Breast Cancer Cells Exposed to OA or Its Derivatives
2.5. Evaluation and Verification of Autophagy Pathway
2.6. Contribution of ER and EGFR to Migration Potential of OA and Its Derivatives in Breast Cancer Cells
2.7. Contribution of OA and Its Derivatives to the Adhesion and Migration of ER− and EGFR− Deprived Breast Cancer Cells
3. Discussion
3.1. OA Derivatives in Cancer Targeting
3.2. The Mechanistic Aspect of OA and Its Derivatives
4. Materials and Methods
4.1. Compounds and Reagents
4.2. Cell Line and Cell Culture
4.2.1. ER Inhibition with Fulvestrant
4.2.2. EGFR Inhibition with Gefitinib
4.3. Viability Assay
4.4. Colony-Formation Assay
4.5. Cell Cycle Analysis by Flow Cytometry
4.6. Immunodetection
4.7. Wound Healing Assay
4.8. Statistical Analysis
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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MCF7 IC50 [µM] | MDA-MB-231 IC50 [µM] | ||||
---|---|---|---|---|---|
Receptor Status | ER+ | ER− | EGFR+ | EGFR− | |
Compound | |||||
OA | 12.7 ± 0.45 | 31.71 ± 2.98 ** | >50 | 22.47 ± 2.49 ** | |
HIMOXOL | 3.22 ± 0.42 | 1.63 ± 0.1 ** | 21 | 1.72 ± 0.08 *** | |
Br-HIMOLID | 6.58 ± 0.74 | 3.53 ± 0.4 ** | >50 | 3.44 ± 0.19 *** |
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Lisiak, N.; Dzikowska, P.; Wisniewska, U.; Kaczmarek, M.; Bednarczyk-Cwynar, B.; Zaprutko, L.; Rubis, B. Biological Activity of Oleanolic Acid Derivatives HIMOXOL and Br-HIMOLID in Breast Cancer Cells Is Mediated by ER and EGFR. Int. J. Mol. Sci. 2023, 24, 5099. https://doi.org/10.3390/ijms24065099
Lisiak N, Dzikowska P, Wisniewska U, Kaczmarek M, Bednarczyk-Cwynar B, Zaprutko L, Rubis B. Biological Activity of Oleanolic Acid Derivatives HIMOXOL and Br-HIMOLID in Breast Cancer Cells Is Mediated by ER and EGFR. International Journal of Molecular Sciences. 2023; 24(6):5099. https://doi.org/10.3390/ijms24065099
Chicago/Turabian StyleLisiak, Natalia, Patrycja Dzikowska, Urszula Wisniewska, Mariusz Kaczmarek, Barbara Bednarczyk-Cwynar, Lucjusz Zaprutko, and Blazej Rubis. 2023. "Biological Activity of Oleanolic Acid Derivatives HIMOXOL and Br-HIMOLID in Breast Cancer Cells Is Mediated by ER and EGFR" International Journal of Molecular Sciences 24, no. 6: 5099. https://doi.org/10.3390/ijms24065099