4 Bacopaside: Exploring Its Potential in Addressing Chemoresistance and Modulating Doxorubicin Accumulation in Triple-Negative Breast Cancer Cells

Publication
Article
Miami Breast Cancer Conference® Abstracts Supplement41st Annual Miami Breast Cancer Conference® - Abstracts
Volume 38
Issue 4
Pages: 8

4 Bacopaside: Exploring Its Potential in Addressing Chemoresistance and Modulating Doxorubicin Accumulation in Triple-Negative Breast Cancer Cells

4 Bacopaside: Exploring Its Potential in Addressing Chemoresistance and Modulating Doxorubicin Accumulation in Triple-Negative Breast Cancer Cells

Introduction

Triple-negative breast cancer (TNBC) is commonly treated with chemotherapy, but resistance and adverse effects pose challenges. Chemoresistance is tied to overexpression of advanced breast cancer advanced breast cancer (ABC) drug transporter genes, including ABCC3. Bacopaside II, from Bacopa monnieri, holds potential against breast cancer, but its role in TNBC drug resistance remains unknown.

Aim

To explore whether bacopaside II counters ABC-related chemoresistance in TNBC by increasing doxorubicin accumulation, potentially improving treatment outcomes.

Methods

Expression of ABC transporter genes (ABCC3, ABCB1, ABCC1, andABCG2) were assessed using TaqMan quantitative reverse transcriptase polymerase chain reaction in TNBC cell lines (DU4475, HCC1143, MDA-MB-231, and MDA-MB-453). Drug impact was assessed for growth inhibition, apoptosis, and membrane integrity alterations. Chemoresistance was induced in the cells via 3-dimensional (3D) culture, and the effect of bacopaside II and cyclosporine A (CsA) in doxorubicin accumulation was measured.

Results

ABCC3 was notably higher in MDA-MB-231 than in HCC1143 (2.7-fold) cells and MDA-MB-453 cells (2.4-fold) and was undetectable in DU4475 cells. ABCC3 correlated with doxorubicin accumulation and sensitivity. Bacopaside II showed varying IC50: DU4475 (23.7 µM), HCC1143 (20.7 µM), MDA-MB-231 (13.5 µM), MDA-MB-453 (19.0 µM). Bacopaside II induced apoptosis ≥15 µM in HCC1143 and both apoptosis and damage (≥15 µM) in MDA-MB-231. Bacopaside II and CsA increased doxorubicin accumulation. Molecular docking suggested strong ABCC3 binding. MDA-MB-231 3D culture increased ABCC3, reduced doxorubicin accumulation, and heightened resistance; combining bacopaside II and doxorubicin improved growth inhibition.

Conclusion

Bacopaside II shows promise in overcoming ABCC3-related chemoresistance, enhancing doxorubicin accumulation, and improving the efficacy of doxorubicin in the treatment of TNBC. Further research into bacopaside II’s potential to improve doxorubicin treatment for TNBC is essential.

Lay Description

Treating breast cancer with chemotherapy is challenging due to resistance and adverse effects. Bacopaside II from Bacopa monnieri might offer a solution. This study investigates bacopaside II’s ability to combat resistance in TNBC, aiming to enhance chemotherapy’s effectiveness by boosting drug levels within cancer cells. Our findings indicate that bacopaside II increased drug concentrations in various TNBC, potentially enhancing treatment. This research proposes bacopaside II as a potential aid for patients with TNBC, although further study is required.

Articles in this issue

1 Centrally Located Breast Cancer Is More Aggressive in Bahraini Patients
1 Centrally Located Breast Cancer Is More Aggressive in Bahraini Patients
2 Is Laterality in Breast Cancer Still Worth Studying? Local Experience in Bahrain
2 Is Laterality in Breast Cancer Still Worth Studying? Local Experience in Bahrain
3 Gender Disparities in the  National Institutes of Health  Funding for Breast Cancer
3 Gender Disparities in the National Institutes of Health Funding for Breast Cancer
4 Bacopaside: Exploring Its Potential in Addressing Chemoresistance and Modulating Doxorubicin Accumulation in Triple-Negative Breast Cancer Cells
4 Bacopaside: Exploring Its Potential in Addressing Chemoresistance and Modulating Doxorubicin Accumulation in Triple-Negative Breast Cancer Cells
5 Predictors of Axillary Complete Pathologic Response in Hormone Receptor–Positive, HER2-Negative, Clinically Node-Positive Breast Cancer
5 Predictors of Axillary Complete Pathologic Response in Hormone Receptor–Positive, HER2-Negative, Clinically Node-Positive Breast Cancer
6 Treatment Outcomes of the KEYNOTE-522 Regimen in an Ethnically Diverse Patient Population
6 Treatment Outcomes of the KEYNOTE-522 Regimen in an Ethnically Diverse Patient Population
7 Real-World Efficacy and Adverse Events of Neoadjuvant Immunotherapy in Early-Stage Triple-Negative Breast Cancer Patients: A Multicenter Experience
7 Real-World Efficacy and Adverse Events of Neoadjuvant Immunotherapy in Early-Stage Triple-Negative Breast Cancer Patients: A Multicenter Experience
8 Using a Liquid Biopsy Mediated Approach for Determination of HER2 Amplification Status in Patient Samples
8 Using a Liquid Biopsy Mediated Approach for Determination of HER2 Amplification Status in Patient Samples
9 Elacestrant (ELA) vs Standard-of-Care (SOC) in ER+/HER2–Advanced (adv) or Metastatic Breast Cancer (mBC) with ESR1 Mutation (ESR1-mut): Key Biomarkers and Clinical Subgroup Analyses From the Phase 3 EMERALD Trial
9 Elacestrant (ELA) vs Standard-of-Care (SOC) in ER+/HER2–Advanced (adv) or Metastatic Breast Cancer (mBC) with ESR1 Mutation (ESR1-mut): Key Biomarkers and Clinical Subgroup Analyses From the Phase 3 EMERALD Trial
10 Real-World Effectiveness of Palbociclib (PAL) Plus Aromatase Inhibitors (AI) in Patients With Metastatic Breast Cancer (MBC) and Cardiovascular Diseases (CVD)
10 Real-World Effectiveness of Palbociclib (PAL) Plus Aromatase Inhibitors (AI) in Patients With Metastatic Breast Cancer (MBC) and Cardiovascular Diseases (CVD)
11 Phase 3 Study of Neoadjuvant Pembrolizumab or Placebo Plus Chemotherapy, Followed by Adjuvant Pembrolizumab or Placebo Plus Endocrine Therapy for Early-Stage High-Risk ER+/HER2– Breast Cancer: KEYNOTE-756
11 Phase 3 Study of Neoadjuvant Pembrolizumab or Placebo Plus Chemotherapy, Followed by Adjuvant Pembrolizumab or Placebo Plus Endocrine Therapy for Early-Stage High-Risk ER+/HER2– Breast Cancer: KEYNOTE-756
12 EMERALD Trial Analysis of Patient-Reported Outcomes (PROs) in Patients (pts) With ER+/HER2- Advanced or Metastatic Breast  Cancer (mBC) Comparing Oral Elacestrant vs Standard-of-Care (SoC) Endocrine Therapy
12 EMERALD Trial Analysis of Patient-Reported Outcomes (PROs) in Patients (pts) With ER+/HER2- Advanced or Metastatic Breast Cancer (mBC) Comparing Oral Elacestrant vs Standard-of-Care (SoC) Endocrine Therapy
13 The Cause and Eradication of Breast Cancer
13 The Cause and Eradication of Breast Cancer
14 Outcomes With First-Line (1L) Ribociclib (RIB) + Endocrine Therapy (ET) vs Physician’s Choice Combination Chemotherapy (combo CT) by Age in Pre/Perimenopausal Patients (pts) With Aggressive HR+/HER2– Advanced Breast Cancer (ABC): A Subgroup Analysis of the RIGHT Choice Trial
14 Outcomes With First-Line (1L) Ribociclib (RIB) + Endocrine Therapy (ET) vs Physician’s Choice Combination Chemotherapy (combo CT) by Age in Pre/Perimenopausal Patients (pts) With Aggressive HR+/HER2– Advanced Breast Cancer (ABC): A Subgroup Analysis of the RIGHT Choice Trial
15 Concurrent Use of Abemaciclib and Radiation Therapy (RT) Among Patients With HR+, HER2– Metastatic Breast Cancer (MBC): Real-World Utilization and Safety
15 Concurrent Use of Abemaciclib and Radiation Therapy (RT) Among Patients With HR+, HER2– Metastatic Breast Cancer (MBC): Real-World Utilization and Safety
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