Enhancement of Doxorubicin Efficacy by Bacopaside II in Triple-Negative Breast Cancer Cells
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 pot...
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2025-01-01
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| Online Access: | https://www.mdpi.com/2218-273X/15/1/55 |
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| author | Sima Kianpour Rad Kenny K. L. Yeo Runhao Li Fangmeinuo Wu Saifei Liu Saeed Nourmohammadi William M. Murphy Yoko Tomita Timothy J. Price Wendy V. Ingman Amanda R. Townsend Eric Smith |
| author_facet | Sima Kianpour Rad Kenny K. L. Yeo Runhao Li Fangmeinuo Wu Saifei Liu Saeed Nourmohammadi William M. Murphy Yoko Tomita Timothy J. Price Wendy V. Ingman Amanda R. Townsend Eric Smith |
| author_sort | Sima Kianpour Rad |
| collection | DOAJ |
| description | 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 (<i>ABCB1</i>, <i>ABCC1</i>, <i>ABCC3</i>, and <i>ABCG2</i>) 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 (<i>ABCB1</i>), 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. |
| format | Article |
| id | doaj-art-16a8860a137142699a504cfd1a899c90 |
| institution | Kabale University |
| issn | 2218-273X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
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| series | Biomolecules |
| spelling | doaj-art-16a8860a137142699a504cfd1a899c902025-01-24T13:25:00ZengMDPI AGBiomolecules2218-273X2025-01-011515510.3390/biom15010055Enhancement of Doxorubicin Efficacy by Bacopaside II in Triple-Negative Breast Cancer CellsSima Kianpour Rad0Kenny K. L. Yeo1Runhao Li2Fangmeinuo Wu3Saifei Liu4Saeed Nourmohammadi5William M. Murphy6Yoko Tomita7Timothy J. Price8Wendy V. Ingman9Amanda R. Townsend10Eric Smith11Solid Tumour Group, Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Central Adelaide Local Health Network, Woodville South, Adelaide, SA 5011, AustraliaSolid Tumour Group, Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Central Adelaide Local Health Network, Woodville South, Adelaide, SA 5011, AustraliaSolid Tumour Group, Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Central Adelaide Local Health Network, Woodville South, Adelaide, SA 5011, AustraliaSolid Tumour Group, Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Central Adelaide Local Health Network, Woodville South, Adelaide, SA 5011, AustraliaSolid Tumour Group, Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Central Adelaide Local Health Network, Woodville South, Adelaide, SA 5011, AustraliaSolid Tumour Group, Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Central Adelaide Local Health Network, Woodville South, Adelaide, SA 5011, AustraliaDepartment of Surgery-Otolaryngology Head and Neck Surgery, The University of Adelaide and the Basil Hetzel Institute for Translational Health Research, Central Adelaide Local Health Network, Adelaide, SA 5000, AustraliaSolid Tumour Group, Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Central Adelaide Local Health Network, Woodville South, Adelaide, SA 5011, AustraliaSolid Tumour Group, Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Central Adelaide Local Health Network, Woodville South, Adelaide, SA 5011, AustraliaAdelaide Medical School, The University of Adelaide, Adelaide, SA 5005, AustraliaSolid Tumour Group, Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Central Adelaide Local Health Network, Woodville South, Adelaide, SA 5011, AustraliaSolid Tumour Group, Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Central Adelaide Local Health Network, Woodville South, Adelaide, SA 5011, AustraliaBackground: 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 (<i>ABCB1</i>, <i>ABCC1</i>, <i>ABCC3</i>, and <i>ABCG2</i>) 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 (<i>ABCB1</i>), 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.https://www.mdpi.com/2218-273X/15/1/55triple-negative breast cancermolecular subtypesbacopaside II<i>Bacopa monnieri</i>doxorubicinchemotherapy |
| spellingShingle | Sima Kianpour Rad Kenny K. L. Yeo Runhao Li Fangmeinuo Wu Saifei Liu Saeed Nourmohammadi William M. Murphy Yoko Tomita Timothy J. Price Wendy V. Ingman Amanda R. Townsend Eric Smith Enhancement of Doxorubicin Efficacy by Bacopaside II in Triple-Negative Breast Cancer Cells Biomolecules triple-negative breast cancer molecular subtypes bacopaside II <i>Bacopa monnieri</i> doxorubicin chemotherapy |
| title | Enhancement of Doxorubicin Efficacy by Bacopaside II in Triple-Negative Breast Cancer Cells |
| title_full | Enhancement of Doxorubicin Efficacy by Bacopaside II in Triple-Negative Breast Cancer Cells |
| title_fullStr | Enhancement of Doxorubicin Efficacy by Bacopaside II in Triple-Negative Breast Cancer Cells |
| title_full_unstemmed | Enhancement of Doxorubicin Efficacy by Bacopaside II in Triple-Negative Breast Cancer Cells |
| title_short | Enhancement of Doxorubicin Efficacy by Bacopaside II in Triple-Negative Breast Cancer Cells |
| title_sort | enhancement of doxorubicin efficacy by bacopaside ii in triple negative breast cancer cells |
| topic | triple-negative breast cancer molecular subtypes bacopaside II <i>Bacopa monnieri</i> doxorubicin chemotherapy |
| url | https://www.mdpi.com/2218-273X/15/1/55 |
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