Classical and atypical resistance of cancer cells as a target for resveratrol
Sylwia Borska1, Monika Pedziwiatr1, Monika Danielewicz1
1Department of Histology and Embryology, Medical University, 50-368 Wroclaw, Poland.
Abstract:
The phenomenon of cancer cell resistance to chemotherapeutics is the main cause of insensitivity to anticancer therapy. Thus, the current challenge remains searching for substances sensitising the activity of cytostatic drugs. In this respect, resveratrol is a very promising therapeutic agent. It has pleiotropic effect on cancer cells, which can play a key role in numerous resistance mechanisms, both classical and atypical. The purpose of the present study was to assess the effect of resveratrol on the inhibition of human pancreatic cancer cell proliferation and on the level of cytostatic resistance-associated proteins. The study was performed on human pancreatic cancer cell lines EPP85-181P (control), EPP85-181RDB (daunorubicin resistance) and EPP85-181PRNOV (mitoxantrone resistance). The effect of resveratrol on the viability and proliferation of the studied cell lines was evaluated by SRB assay, whereas cell cycle arrest and cytostatic accumulation by FACS. Western blot analysis was used to determine the level of P-glycoprotein, topoisomerase II α and β and immunofluorescence technique to visualise the proteins in the cells. Resveratrol inhibited proliferation of all studied cell lines. Phase-specific cell cycle arrest depended on the type of cancer cells. Resveratrol decreased the level and activity of P-gp in EPP85-181RDB cells. In EPP85-181PRNOV cells, expression of both TopoII isoforms increased in a statistically significant manner. The results of in vitro studies support the possibility of potential use of resveratrol in breaking cancer cell resistance to chemotherapeutic drugs.
Insights
Resveratrol shows promise in overcoming cancer cell resistance to chemotherapy by inhibiting proliferation and affecting key resistance proteins. This natural compound may help sensitize cancer cells to existing anticancer drugs.
Area of Science:
- Oncology
- Pharmacology
- Biochemistry
Background:
- Cancer cell resistance to chemotherapy is a major obstacle in effective anticancer therapy.
- Identifying agents that can resensitize cancer cells to chemotherapeutics is a critical research area.
- Resveratrol, a natural polyphenol, exhibits pleiotropic effects on cancer cells and is being investigated for its potential in overcoming drug resistance.
Purpose of the Study:
- To evaluate the efficacy of resveratrol in inhibiting human pancreatic cancer cell proliferation.
- To assess the impact of resveratrol on the levels of proteins associated with cytostatic drug resistance.
- To investigate resveratrol's potential to overcome chemoresistance in specific pancreatic cancer cell lines.
Main Methods:
- Utilized human pancreatic cancer cell lines with varying resistance profiles (EPP85-181P, EPP85-181RDB, EPP85-181PRNOV).
- Assessed cell viability and proliferation using the Sulforhodamine B (SRB) assay.
- Analyzed cell cycle arrest and protein expression (P-glycoprotein, Topoisomerase II α/β) via Flow Cytometry (FACS) and Western blot analysis, respectively.
- Visualized protein localization using immunofluorescence techniques.
Main Results:
- Resveratrol demonstrated significant inhibition of proliferation across all tested pancreatic cancer cell lines.
- Resveratrol reduced the expression and activity of P-glycoprotein (P-gp) in daunorubicin-resistant cells (EPP85-181RDB).
- A statistically significant increase in both isoforms of Topoisomerase II (TopoII) was observed in mitoxantrone-resistant cells (EPP85-181PRNOV) upon resveratrol treatment.
Conclusions:
- Resveratrol effectively inhibits pancreatic cancer cell proliferation in vitro.
- Resveratrol modulates key proteins involved in chemoresistance, including P-glycoprotein and Topoisomerase II.
- These findings suggest that resveratrol holds potential as an adjuvant therapy to overcome cancer cell resistance to chemotherapeutic drugs.
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