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Updated: Aug 23, 2025
Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
Published on: February 6, 2015
Curcumin Sensitizes 4T1 Murine Breast Cancer Cells to Cisplatin Through PAR4 Secretion
Norma Cesilia Arellano-Rodríguez1, Oscar Alberto Alvarez-Quezada1, Pablo Zapata Benavides2
1Department of Microbiology and Immunology, School of Biological Sciences, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, Mexico.
Background/Aim:
Prostate apoptosis response 4 (PAR4), a tumour-suppressor protein, selectively induces apoptosis of cancer cells without affecting normal cells. Its soluble form is induced by secretagogues (e.g., chloroquine), and it induces apoptosis by interacting with the receptor of glucose-regulated protein 78, which is overexpressed in cancer cells. In this study, curcumin was analyzed as an inducer of PAR4 expression in 4T1 murine breast cancer cell. and its ability to induce PAR4 secretion in Balb/c mice. In addition, the cisplatin sensitizing effect of soluble PAR4 was analyzed.
Material And Methods:
The 4T1 cell line was treated in vitro using different concentrations of curcumin; cell viability was analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and PAR4 expression by western blotting. The expression of soluble PAR4 in the serum of mice treated with intraperitoneal curcumin was analyzed using the dot-blot method. Moreover, MTT assay was used to analyze the effects of serum from curcumin-treated mice on cell viability. Tumor size was analyzed in mice treated with curcumin alone and in combination with cisplatin.
Results:
Curcumin showed a dose- and time-dependent effects on cell viability on 4T1 cells, as well as increasing PAR4 expression. Compared with the control group (phosphate-buffered saline), mice treated with curcumin showed an increase in plasma PAR4. In the Balb/C tumor model, mice treated with curcumin and cisplatin showed greater tumor shrinkage than the control group.
Conclusion:
These results indicate that curcumin induces expression of soluble PAR4 and sensitizes tumor cells to cisplatin.
Insights
Curcumin boosts the expression of soluble Prostate Apoptosis Response 4 (PAR4), a protein that kills cancer cells. This enhances cisplatin
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Prostate apoptosis response 4 (PAR4) is a tumor suppressor protein that selectively induces cancer cell apoptosis.
- Soluble PAR4 interacts with glucose-regulated protein 78 (GRP78) receptors, which are overexpressed in cancer cells.
- Secretagogues like chloroquine can induce soluble PAR4.
Purpose of the Study:
- To investigate curcumin as an inducer of PAR4 expression in 4T1 murine breast cancer cells.
- To assess curcumin's ability to induce PAR4 secretion in Balb/c mice.
- To evaluate the cisplatin-sensitizing effect of soluble PAR4.
Main Methods:
- In vitro treatment of 4T1 cells with varying curcumin concentrations.
- Analysis of cell viability (MTT assay) and PAR4 expression (Western blotting).
- Dot-blot analysis of soluble PAR4 in serum from curcumin-treated mice.
- Tumor size assessment in mice treated with curcumin alone and with cisplatin.
Main Results:
- Curcumin demonstrated dose- and time-dependent effects on 4T1 cell viability and increased PAR4 expression.
- Curcumin treatment led to elevated plasma PAR4 levels in mice compared to controls.
- Combination therapy with curcumin and cisplatin resulted in significant tumor shrinkage in the Balb/C model.
Conclusions:
- Curcumin effectively induces the expression of soluble PAR4.
- Curcumin sensitizes tumor cells to cisplatin chemotherapy.
- This suggests a potential therapeutic strategy combining curcumin with cisplatin for breast cancer treatment.
