ArticleInternational journal of molecular sciences2020
Flavonoids Restore Platinum Drug Sensitivity to Ovarian Carcinoma Cells in a Phospho-ERK1/2-Dependent Fashion.
Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 26 citations in OpenAlex.
- Review
- Nanotechnology-Enhanced Delivery and Bioactivity of Dietary Flavonoids: Overcoming Bioavailability Barriers for Targeted Antimicrobial and Antiviral Therapies-A Comprehensive Review.International journal of nanomedicine · 2026Review
- Exploring miRNA profile associated with cisplatin resistance in ovarian cancer cells.Biochemistry and biophysics reports · 2025Article
- The JPX/miR-495-3p/BRD4 axis mediates quercetin-induced toxicity via the X-inactivation center in NSCLC.Current research in toxicology · 2025Article
- Knockdown of TIM1 enhances platinum chemosensitivity and inhibits progression through the MAPK signaling pathway in gastric cancer.American journal of translational research · 2025Article
- Nutritional Strategy for Cancer-From Prevention to Aftercare.Nutrients · 2024Article
- Bitter taste receptors in the reproductive system: Function and therapeutic implications.Journal of cellular physiology · 2024Review
- Quercetin Promote the Chemosensitivity in Organoids Derived from Patients with Breast Cancer.Breast cancer (Dove Medical Press) · 2024Article
- Causal effect analysis of estrogen receptor associated breast cancer and clear cell ovarian cancer.American journal of translational research · 2024Article
- Role of Fisetin in Selected Malignant Neoplasms in Women.Nutrients · 2023Review
- Caffeic Acid Phenethyl Ester (CAPE) Synergistically Enhances Paclitaxel Activity in Ovarian Cancer Cells.Molecules (Basel, Switzerland) · 2023Article
- Secreted Soluble Factors from Tumor-Activated Mesenchymal Stromal Cells Confer Platinum Chemoresistance to Ovarian Cancer Cells.International journal of molecular sciences · 2023Article
- Association of variations in theFrontiers in pharmacology · 2023Article
- 2-Hydroxyestradiol Overcomes Mesenchymal Stem Cells-Mediated Platinum Chemoresistance in Ovarian Cancer Cells in an ERK-Independent Fashion.Molecules (Basel, Switzerland) · 2022Article
- Quercetin and polycystic ovary syndrome.Frontiers in pharmacology · 2022Review
- Detailed Molecular Mechanism and Potential Drugs for COL1A1 in Carboplatin-Resistant Ovarian Cancer.Frontiers in oncology · 2020Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ovarian cancer (OC) is the second most common type of gynecological malignancy; it has poor survival rates and is frequently (>75%) diagnosed at an advanced stage. Platinum-based chemotherapy, with, e.g., carboplatin, is the standard of care for OC, but toxicity and acquired resistance to therapy have proven challenging. Despite advances in OC diagnosis and treatment, approximately 85% of patients will experience relapse, mainly due to chemoresistance. The latter is attributed to alterations in the cancer cells and is also mediated by tumor microenvironment (TME). Recently, we reported the synthesis of a platinum (IV) prodrug that exhibits equal potency toward platinum-sensitive and resistant OC cell lines. Here, we investigated the effect of TME on platinum sensitivity. Co-culture of OC cells with murine or human mesenchymal stem cells (MS-5 and HS-5, respectively) rendered them resistant to chemotherapeutic agents, including platinum, paclitaxel and colchicine. Platinum resistance was also conferred by co-culture with differentiated murine adipocyte progenitor cells. Exposure of OC cells to chemotherapeutic agents resulted in activation of phospho-ERK1/2. Co-culture with MS-5, which conferred drug resistance, was accompanied by blockage of phospho-ERK1/2 activation. The flavonoids fisetin and quercetin were active in restoring ERK phosphorylation, as well as sensitivity to platinum compounds. Exposure of OC cells to cobimetinib-a MEK1 inhibitor that also inhibits extracellular signal-regulated kinase (ERK) phosphorylation-which resulted in reduced sensitivity to the platinum compound. This suggests that ERK activity is involved in mediating the function of flavonoids in restoring platinum sensitivity to OC co-cultured with cellular components of the TME. Our data show the potential of combining flavonoids with standard therapy to restore drug sensitivity to OC cells and overcome TME-mediated platinum drug resistance.
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