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Updated: Nov 24, 2025
Evaluation of Stem Cell Properties in Human Ovarian Carcinoma Cells Using Multi and Single Cell-based Spheres Assays
Published on: January 3, 2015
Exploiting the antiproliferative potential of spiropyrazoline oxindoles in a human ovarian cancer cell line
Luís R Raposo1, Ana Silva1, Dário Silva2
1UCIBIO, Departamento de Ciências da Vida, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, Campus de Caparica, 2829-516 Caparica, Portugal.
Abstract:
Cancer is still one of the deadliest diseases worldwide despite the efforts in its early detection and treatment strategies. However, most chemotherapeutic agents still present side effects in normal tissues and acquired resistance that limit their efficacy. Spiropyrazoline oxindoles might be good alternatives as they have shown antiproliferative activity in human breast and colon cancer cell lines, without eliciting cytotoxicity in healthy cells. However, their potential for ovarian cancer was never tested. In this work, the antiproliferative activity of five spiropyrazoline oxindoles was assessed in ovarian cancer cells A2780 and the biological targets and mechanism of action of the most promising compound evaluated. Compound 1a showed the highest antiproliferative effect, as well as the highest selectivity for A2780 cells compared to healthy fibroblasts. This antiproliferative effect results from the induction of cell death by mitochondria-mediated apoptosis and autophagy. In vitro DNA interaction studies demonstrated that 1a interacts with DNA by groove-binding, without triggering genotoxicity. In addition, 1a showed a strong affinity to bovine serum albumin that might be important for further inclusion in drug delivery platforms. Proteomic studies reinforced 1a role in promoting A2780 endoplasmatic reticulum (ER) stress by destabilizing the correct protein folding which triggers cell death via apoptosis and autophagy.
Insights
New spiropyrazoline oxindoles show potent antiproliferative effects against ovarian cancer cells. Compound 1a selectively induces apoptosis and autophagy, offering a promising alternative to traditional chemotherapy.
Area of Science:
- Medicinal Chemistry
- Molecular Biology
- Cancer Research
Background:
- Cancer remains a leading cause of death globally, with chemotherapy facing challenges like side effects and resistance.
- Spiropyrazoline oxindoles exhibit antiproliferative properties in breast and colon cancer cells, with minimal toxicity to healthy cells.
- The therapeutic potential of spiropyrazoline oxindoles in ovarian cancer has not been previously investigated.
Purpose of the Study:
- To evaluate the antiproliferative activity of novel spiropyrazoline oxindoles against ovarian cancer.
- To identify the most effective compound and elucidate its mechanism of action and biological targets.
- To assess the compound's interaction with DNA and serum albumin for potential drug delivery applications.
Main Methods:
- Antiproliferative assays were performed on A2780 ovarian cancer cells and healthy fibroblasts.
- Mechanism of action studies involved evaluating apoptosis, autophagy, DNA interaction, and proteomic analysis.
- Compound 1a was assessed for its affinity to bovine serum albumin.
Main Results:
- Compound 1a demonstrated significant antiproliferative activity and selectivity towards A2780 cells over healthy fibroblasts.
- The compound induced cancer cell death through mitochondria-mediated apoptosis and autophagy.
- In vitro studies confirmed DNA groove-binding interaction without genotoxicity and showed high affinity to bovine serum albumin.
- Proteomic analysis revealed that compound 1a induces endoplasmic reticulum (ER) stress in A2780 cells.
Conclusions:
- Compound 1a is a highly selective and potent antiproliferative agent against ovarian cancer cells.
- Its mechanism involves inducing apoptosis and autophagy via ER stress and mitochondria-mediated pathways.
- Compound 1a's favorable DNA interaction and serum albumin binding suggest potential for drug development and delivery systems.
