Enhancement of Doxorubicin Efficacy by Bacopaside II in Triple-Negative Breast Cancer Cells
Sima Kianpour Rad1,2, Kenny K L Yeo1,2, Runhao Li1,2
1Solid Tumour Group, Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Central Adelaide Local Health Network, Woodville South, Adelaide, SA 5011, Australia.
Background:
Triple-negative breast cancer (TNBC) is an aggressive subtype with limited treatment options and high resistance to chemotherapy. Doxorubicin is commonly used, but its efficacy is limited by variable sensitivity and resistance. Bacopaside II, a saponin compound, has shown anti-cancer potential. This study evaluates the effects of doxorubicin and bacopaside II, both individually and in combination, across TNBC subtypes to explore mechanisms of resistance and enhanced drug efficacy.
Methods:
The growth-inhibitory effects of doxorubicin and bacopaside II were assessed in four TNBC cell lines. IC50 values were determined using dose-response assays, and doxorubicin accumulation was measured via spectral flow cytometry. ATP-binding cassette (ABC) transporter expression (ABCB1, ABCC1, ABCC3, and ABCG2) was analyzed for correlations with drug sensitivity. In silico docking assessed the binding affinity of bacopaside II to ABC transporters. A 3D culture model simulated drug-resistant TNBC, and combination effects were evaluated with live-cell imaging.
Results:
Doxorubicin sensitivity varied across TNBC molecular subtypes, correlating to intracellular accumulation. Bacopaside II inhibited growth across subtypes, inducing apoptosis in sensitive cells and necrosis in resistant cells. Bacopaside II increased doxorubicin accumulation, independent of P-glycoprotein (ABCB1), possibly through interactions with other ABC transporters. In drug-resistant 3D cultures, bacopaside II maintained efficacy and enhanced doxorubicin accumulation, counteracting ABC transporter-mediated resistance. The doxorubicin and bacopaside II combination showed synergistic growth inhibition.
Conclusions:
Bacopaside II enhances doxorubicin efficacy in TNBC by increasing drug accumulation and overcoming ABC transporter-mediated resistance, suggesting its potential as an adjuvant in TNBC treatment. These findings support further investigation of bacopaside II, particularly for resistant TNBC subtypes.
Insights
Bacopaside II enhances doxorubicin treatment for triple-negative breast cancer (TNBC) by increasing drug accumulation and overcoming resistance. This suggests its potential as an adjuvant therapy for TNBC.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Triple-negative breast cancer (TNBC) is aggressive, with limited chemotherapy options and high drug resistance.
- Doxorubicin efficacy in TNBC is hampered by variable sensitivity and resistance mechanisms.
- Bacopaside II, a natural saponin, exhibits anti-cancer properties warranting investigation.
Purpose of the Study:
- To evaluate the individual and combined effects of doxorubicin and bacopaside II on TNBC cell lines.
- To explore the mechanisms underlying drug resistance in TNBC.
- To assess bacopaside II's potential to enhance doxorubicin efficacy and overcome resistance.
Main Methods:
- Assessed growth inhibition and IC50 values of doxorubicin and bacopaside II in four TNBC cell lines.
- Measured doxorubicin accumulation and analyzed ATP-binding cassette (ABC) transporter expression (ABCB1, ABCC1, ABCC3, ABCG2).
- Utilized in silico docking, a 3D culture model of drug-resistant TNBC, and live-cell imaging for combination studies.
Main Results:
- Doxorubicin sensitivity varied among TNBC subtypes, correlating with intracellular drug accumulation.
- Bacopaside II inhibited TNBC growth, inducing apoptosis or necrosis depending on cell sensitivity, and increased doxorubicin accumulation.
- Bacopaside II counteracted ABC transporter-mediated resistance in 3D cultures, showing synergistic growth inhibition with doxorubicin.
Conclusions:
- Bacopaside II enhances doxorubicin efficacy in TNBC by increasing drug accumulation and overcoming ABC transporter-mediated resistance.
- Bacopaside II shows potential as an adjuvant therapy for TNBC, especially for resistant subtypes.
- Further research into bacopaside II for TNBC treatment is warranted.
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