The Divergent Effects of Ovarian Steroid Hormones in the MCF-7 Model for Luminal A Breast Cancer: Mechanistic Leads for Therapy
Abstract
:1. Introduction
2. Cellular Models
2.1. The Growth Characteristics of the MCF-7 Model
2.2. Growth Modulation by Estradiol and Progesterone
2.3. Cell Cycle Progression and Cellular Apoptosis
3. Hormone Metabolism
3.1. Cellular Metabolism of Estradiol
3.2. The Cellular Metabolism of Progesterone
4. Efficacy of Natural Products
5. Drug-Resistant Stem Cells
6. Stem Cell Targeting Agents
7. Conclusions
8. Future Prospects
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Model | Receptor Status | Subtype | References | ||
---|---|---|---|---|---|
ER | PR | HER-2 | |||
MCF-7 | + | + | − | Luminal A | [12,13] |
T47D | + | + | − | Luminal A | [12,13] |
BT474 | + | + | + | Luminal B | [12,13] |
MDA-MB-361 | + | + | + | Luminal B | [12,13] |
MCF-7 HER | + | + | + | Luminal B | [14] |
MCF-7AROM | + | + | − | Aromatase positive | [15,16] |
SKBr-3 | − | − | + | HER-2 enriched | [12,13] |
184-B5/HER | − | − | + | HER-2 enriched | [17,18] |
MDA-MB-231 | − | − | − | Triple negative | [12,13] |
End-Point Biomarker | Experimental Model | ||
---|---|---|---|
184-B5 | MCF-7 | Relative to 184-B5 | |
Population doubling (h) | 34.0 ± 1.8 | 15.2 ± 0.9 | −55.3% |
Saturation density (×105) | 22.3 ± 1.2 | 26.6 ± 1.7 | +19.3% |
G1:S + G2/M ratio | 2.3 ± 0.3 | 1.4 ± 0.4 | −39.1% |
Sub G0 population (%) | 14.8 ± 2.3 | 2.8 ± 1.4 | −81.1% |
2-OHE1:16α-OHE1 ratio | 6.4 ± 0.8 | 0.4 ± 0.2 | −93.7% |
AI colonies | 0/18 | 18/18 | +100% |
Model | Relative Cancer Risk | 2-OHE1:16α-OHE1 Ratio | Relative to Low Risk |
---|---|---|---|
TDLU reduction mammoplasty | Low | 4.8 ± 0.6 | - |
TDLU breast cancer | High | 0.3 ± 0.1 | −93.7% |
184-B5 breast epithelial cells | Low | 6.4 ± 0.8 | - |
184-B5/HER HER-2 positive | High | 0.6 ± 0.3 | −90.6% |
MCF-7 breast carcinoma | High | 0.3 ± 0.1 | −95.3% |
MMEC mouse mammary epithelial Cells | Low | 2.2 ± 0.3 | - |
MMEC-Ras Ras positive | High | 0.2 ± 0.1 | −90.9% |
MMEC-Myc Myc positive | High | 0.3 ± 0.1 | −86.4% |
Treatment | Source | Concentration | 2-OHE1:16α-OHE1 Ratio | Relative to E2 Control |
---|---|---|---|---|
E2 control | 20 nM | 0.4 ± 0.2 | - | |
E2 + EG | Leaf/stem | 20 nM + 9.0 µg/mL | 1.9 ± 0.2 | +3.7x |
E2 + LB | Bark | 20 nM + 0.5 µg/mL | 5.2 ± 0.7 | +12.0x |
E2 + CO | Fruit | 20 nM + 5.0 µg/mL | 6.8 ± 0.8 | +16.0x |
Targeted Therapy | Cellular Model | Therapeutic Alternative |
---|---|---|
SERM, SERD, AI, CDKI, HERI | Luminal A: HR+ HER-2− MCF-7 Luminal B: HR+ HER-2+ MCF-7/HER Post-menopausal: aromatase positive MCF-7 AROM | Natural phytochemicals nutritional herbs Documented human consumption Lack of detectable systemic toxicity |
Systemic toxicity, acquired tumor resistance, drug-resistant stem cell population | Luminal B: HR+ HER-2+ MCF-7/HER Post-menopausal: aromatase positive MCF-7 AROM | Inhibited proliferation. Increased 2-OHE1 |
Proliferation: increased by E2 Decreased by PRG | ||
E2 metabolites: proliferative metabolites increased, anti-proliferative metabolites decreased PRG metabolites: proliferative metabolites decreased, anti-proliferative metabolites increased | ||
TAM-R stem cells: TS increased CD44, NANOG, and OCT-4 increased | ||
Future directions: novel pharmacological inhibitors specific for RAS, PI3K, and AKT signaling pathways. Efficacy of small molecule inhibitors on developed stem cell models. Safety and efficacy in Phase 0 clinical trials | Future directions: stem cell models from therapy-resistant PDTX and PDTO. Cellular and molecular characterization of developed stem cell models | Future directions: efficacy of natural phytochemicals and nutritional herbs on PDTX- and PDTO-derived stem cell models. |
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Telang, N.T. The Divergent Effects of Ovarian Steroid Hormones in the MCF-7 Model for Luminal A Breast Cancer: Mechanistic Leads for Therapy. Int. J. Mol. Sci. 2022, 23, 4800. https://doi.org/10.3390/ijms23094800
Telang NT. The Divergent Effects of Ovarian Steroid Hormones in the MCF-7 Model for Luminal A Breast Cancer: Mechanistic Leads for Therapy. International Journal of Molecular Sciences. 2022; 23(9):4800. https://doi.org/10.3390/ijms23094800
Chicago/Turabian StyleTelang, Nitin T. 2022. "The Divergent Effects of Ovarian Steroid Hormones in the MCF-7 Model for Luminal A Breast Cancer: Mechanistic Leads for Therapy" International Journal of Molecular Sciences 23, no. 9: 4800. https://doi.org/10.3390/ijms23094800