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Multidrug resistance phenotype: Relation between phenotype induction and its characteristics in erythroleukemia cells
Fernanda Saldanha Soares1,2, Aline Portantiolo Lettnin1,2, Eduardo Felipe Wagner2,3
1Programa de Pós-Graduação em Ciências Fisiológicas, Instituto de Ciências Biológicas, Universidade Federal do Rio Grande- FURG, Av. Itália, Km 8, CEP 96203-900 Rio Grande, RS, Brasil.
Abstract:
Chemotherapy may be followed by multiple drug resistance (MDR). This is an obstacle in the treatment of cancer. It is therefore essential to understand the mechanisms underlying tumor resistance, especially those involved in the cell target/MDR relationship. To investigate this, the effects of exposing cells to UVB (to target DNA), UVA, and H2 O2 (to target the cell membrane) were observed in K562 (non MDR) and FEPS (MDR) cell lines. The K562 cells were more sensitive to UVA than the FEPS cells. The FEPS cell line was more resistant to H2 O2 than K562, only presenting cytotoxicity 72 h after being exposed to 40 mM, with no ROS increase until 48 h. Both cell lines were sensitive to UVB, presenting cytotoxicity after 24 h, mainly by apoptosis, and showed an increase in ROS levels. Our results indicate that agents acting on DNA may be able to overcome the MDR phenotype.
Insights
Agents targeting DNA may overcome multiple drug resistance (MDR) in cancer. UVB exposure induced apoptosis and reactive oxygen species (ROS) in both sensitive and MDR cells, suggesting a potential therapeutic strategy.
Area of Science:
- Molecular Biology
- Cancer Research
- Cell Biology
Background:
- Multiple drug resistance (MDR) is a significant obstacle in cancer chemotherapy.
- Understanding the mechanisms of tumor resistance, particularly the cell target/MDR relationship, is crucial for effective cancer treatment.
Purpose of the Study:
- To investigate the mechanisms underlying tumor resistance in cancer cells.
- To compare the effects of different damaging agents (UVB, UVA, H2O2) on drug-sensitive and MDR cancer cell lines.
Main Methods:
- Exposure of K562 (non-MDR) and FEPS (MDR) cell lines to UVB, UVA, and hydrogen peroxide (H2O2).
- Assessment of cytotoxicity, apoptosis, and reactive oxygen species (ROS) levels.
- Comparative analysis of cellular responses between sensitive and MDR cell lines.
Main Results:
- K562 cells showed higher sensitivity to UVA compared to FEPS cells.
- FEPS cells exhibited greater resistance to H2O2, with delayed cytotoxicity and no ROS increase until 48 hours.
- Both cell lines were sensitive to UVB, inducing cytotoxicity via apoptosis and increasing ROS levels within 24 hours.
Conclusions:
- Agents that specifically target DNA, such as UVB, may be effective in overcoming the multiple drug resistance (MDR) phenotype.
- Differential cellular responses to UVA and H2O2 highlight distinct resistance mechanisms in MDR cells.
- Targeting DNA damage pathways presents a promising strategy for enhancing cancer chemotherapy efficacy against resistant tumors.
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