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Cucurbitacin B Causes Increased Radiation Sensitivity of Human Breast Cancer Cells via G2/M Cell Cycle Arrest.

Duangmano S, Sae-Lim P, Suksamrarn A, Patmasiriwat P, Domann FE - J Oncol (2012)

Bottom Line: Results.Flow cytometric analysis for DNA content indicated that cucurbitacin B resulted in G2/M arrest in MDA-MB-231 and MCF7:5C but not SKBR-3 cells.Therefore, combinations of cucurbitacin B with radiotherapy may be appropriate for experimental breast cancer treatment.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Medical Technology, Mahidol University, Bangkok, Thailand.

ABSTRACT
Purpose. To explore the effects of cucurbitacin B on the radiation survival of human breast cancer cells and to elucidate the cellular mechanism of radiosensitization if any. Materials and Methods. Human breast carcinoma cell lines were treated with cucurbitacin B before irradiation with 0-10 Gy of (137)Cs gamma rays. The effect of cucurbitacin B on cell-survival following irradiation was evaluated by colony-forming assay. Cell cycle distributions were investigated using flow cytometry. Real-time PCR and western blots were performed to investigate the expression of cell cycle checkpoints. Results. Cucurbitacin B inhibited breast cancer cell proliferation in a dose-dependent manner. Only MDA-MB-231 and MCF7:5C cells but not SKBR-3 cells were radiosensitized by cucurbitacin B. Flow cytometric analysis for DNA content indicated that cucurbitacin B resulted in G2/M arrest in MDA-MB-231 and MCF7:5C but not SKBR-3 cells. Moreover, Real-time PCR and western blot analysis demonstrated upregulated p21 expression before irradiation, a likely cause of the cell cycle arrest. Conclusion. Taken together, these findings suggest that cucurbitacin B causes radiosensitization of some breast cancer cells, and that cucurbitacin B induced G2/M arrest is an important mechanism. Therefore, combinations of cucurbitacin B with radiotherapy may be appropriate for experimental breast cancer treatment.

No MeSH data available.


Related in: MedlinePlus

Effect of cucurbitacin B on p21 protein expression in breast cancer cells. (a) Cells were treated with cucurbitacin B for 48 hr, and then the total proteins were extracted and performed western blotting to analyze p21 expression. Tubulin was used as an equal loading control. (b) Densitometric analyses of expression of p21 relative to the untreated control. *P < 0.05 versus nontreated control, **P < 0.01 versus nontreated control.
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fig5: Effect of cucurbitacin B on p21 protein expression in breast cancer cells. (a) Cells were treated with cucurbitacin B for 48 hr, and then the total proteins were extracted and performed western blotting to analyze p21 expression. Tubulin was used as an equal loading control. (b) Densitometric analyses of expression of p21 relative to the untreated control. *P < 0.05 versus nontreated control, **P < 0.01 versus nontreated control.

Mentions: We examined the effect of cucurbitacin B on the expression of cell cycle regulated protein by western blot analysis. Cells were incubated with the indicated concentration of cucurbitacin B for 48 hr and total protein were extracted for western blot analysis. As shown in Figure 5, protein expression of cyclin-dependent kinase inhibitor p21 was significantly increased following cucurbitacin B treatment in all study cells. SKBR-3 cells, which showed the highest mRNA accumulation in response to cucurbitacin B, also showed the greatest induction of the p21 protein; however, this was not necessarily linked to G2/M arrest or radiation sensitization by cucurbitacin B.


Cucurbitacin B Causes Increased Radiation Sensitivity of Human Breast Cancer Cells via G2/M Cell Cycle Arrest.

Duangmano S, Sae-Lim P, Suksamrarn A, Patmasiriwat P, Domann FE - J Oncol (2012)

Effect of cucurbitacin B on p21 protein expression in breast cancer cells. (a) Cells were treated with cucurbitacin B for 48 hr, and then the total proteins were extracted and performed western blotting to analyze p21 expression. Tubulin was used as an equal loading control. (b) Densitometric analyses of expression of p21 relative to the untreated control. *P < 0.05 versus nontreated control, **P < 0.01 versus nontreated control.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3368438&req=5

fig5: Effect of cucurbitacin B on p21 protein expression in breast cancer cells. (a) Cells were treated with cucurbitacin B for 48 hr, and then the total proteins were extracted and performed western blotting to analyze p21 expression. Tubulin was used as an equal loading control. (b) Densitometric analyses of expression of p21 relative to the untreated control. *P < 0.05 versus nontreated control, **P < 0.01 versus nontreated control.
Mentions: We examined the effect of cucurbitacin B on the expression of cell cycle regulated protein by western blot analysis. Cells were incubated with the indicated concentration of cucurbitacin B for 48 hr and total protein were extracted for western blot analysis. As shown in Figure 5, protein expression of cyclin-dependent kinase inhibitor p21 was significantly increased following cucurbitacin B treatment in all study cells. SKBR-3 cells, which showed the highest mRNA accumulation in response to cucurbitacin B, also showed the greatest induction of the p21 protein; however, this was not necessarily linked to G2/M arrest or radiation sensitization by cucurbitacin B.

Bottom Line: Results.Flow cytometric analysis for DNA content indicated that cucurbitacin B resulted in G2/M arrest in MDA-MB-231 and MCF7:5C but not SKBR-3 cells.Therefore, combinations of cucurbitacin B with radiotherapy may be appropriate for experimental breast cancer treatment.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Medical Technology, Mahidol University, Bangkok, Thailand.

ABSTRACT
Purpose. To explore the effects of cucurbitacin B on the radiation survival of human breast cancer cells and to elucidate the cellular mechanism of radiosensitization if any. Materials and Methods. Human breast carcinoma cell lines were treated with cucurbitacin B before irradiation with 0-10 Gy of (137)Cs gamma rays. The effect of cucurbitacin B on cell-survival following irradiation was evaluated by colony-forming assay. Cell cycle distributions were investigated using flow cytometry. Real-time PCR and western blots were performed to investigate the expression of cell cycle checkpoints. Results. Cucurbitacin B inhibited breast cancer cell proliferation in a dose-dependent manner. Only MDA-MB-231 and MCF7:5C cells but not SKBR-3 cells were radiosensitized by cucurbitacin B. Flow cytometric analysis for DNA content indicated that cucurbitacin B resulted in G2/M arrest in MDA-MB-231 and MCF7:5C but not SKBR-3 cells. Moreover, Real-time PCR and western blot analysis demonstrated upregulated p21 expression before irradiation, a likely cause of the cell cycle arrest. Conclusion. Taken together, these findings suggest that cucurbitacin B causes radiosensitization of some breast cancer cells, and that cucurbitacin B induced G2/M arrest is an important mechanism. Therefore, combinations of cucurbitacin B with radiotherapy may be appropriate for experimental breast cancer treatment.

No MeSH data available.


Related in: MedlinePlus