Limits...
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

Clonogenic survival of breast cancer cells after treatment including irradiation with or without cucurbitacin B. MCF7:5C, MDA-MB-231, and SKBR-3 cells were treated with 5 μM of cucurbitacin B for 48 hr before radiation. Following the incubation period with specific drug concentration, cells were harvested, resuspended in fresh medium, and then irradiated at 0–8 Gy. Colony formation was detected by 21 days later and survival curve was constructed. Data was a summary of three experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3368438&req=5

fig6: Clonogenic survival of breast cancer cells after treatment including irradiation with or without cucurbitacin B. MCF7:5C, MDA-MB-231, and SKBR-3 cells were treated with 5 μM of cucurbitacin B for 48 hr before radiation. Following the incubation period with specific drug concentration, cells were harvested, resuspended in fresh medium, and then irradiated at 0–8 Gy. Colony formation was detected by 21 days later and survival curve was constructed. Data was a summary of three experiments.

Mentions: To determine whether cucurbitacin B sensitized human breast cancer cells to ionizing radiation, all three cell lines were treated with 5 μM cucurbitacin B for 48 hr following irradiation with a 137Cs gamma-irradiator at doses ranging 0–8 Gy. The cells were then allowed to form colonies in fresh medium. The plating efficiency of all cells was between 60 and 80%. Figure 6 shows the radiation survival curves derived from clonogenic assays of the three cell lines irradiated after 48 hr incubation with cucurbitacin B. The latter slope of survival curve of MCF7:C and MDA-MB-231 cells for radiation and cucurbitacin B treated were greater than radiation only, especially at the 6 and 8 Gy radiation doses, indicating that cucurbitacin B treatment augmented the effects of radiation in both cell lines where G2/M arrest was observed to occur. However, SKBR-3 did not show to augment the effects of radiation, consistent with the cell cycle distribution shown in Figure 2 and the absence of a G2/M arrest in SKBR-3 cells.


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)

Clonogenic survival of breast cancer cells after treatment including irradiation with or without cucurbitacin B. MCF7:5C, MDA-MB-231, and SKBR-3 cells were treated with 5 μM of cucurbitacin B for 48 hr before radiation. Following the incubation period with specific drug concentration, cells were harvested, resuspended in fresh medium, and then irradiated at 0–8 Gy. Colony formation was detected by 21 days later and survival curve was constructed. Data was a summary of three experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig6: Clonogenic survival of breast cancer cells after treatment including irradiation with or without cucurbitacin B. MCF7:5C, MDA-MB-231, and SKBR-3 cells were treated with 5 μM of cucurbitacin B for 48 hr before radiation. Following the incubation period with specific drug concentration, cells were harvested, resuspended in fresh medium, and then irradiated at 0–8 Gy. Colony formation was detected by 21 days later and survival curve was constructed. Data was a summary of three experiments.
Mentions: To determine whether cucurbitacin B sensitized human breast cancer cells to ionizing radiation, all three cell lines were treated with 5 μM cucurbitacin B for 48 hr following irradiation with a 137Cs gamma-irradiator at doses ranging 0–8 Gy. The cells were then allowed to form colonies in fresh medium. The plating efficiency of all cells was between 60 and 80%. Figure 6 shows the radiation survival curves derived from clonogenic assays of the three cell lines irradiated after 48 hr incubation with cucurbitacin B. The latter slope of survival curve of MCF7:C and MDA-MB-231 cells for radiation and cucurbitacin B treated were greater than radiation only, especially at the 6 and 8 Gy radiation doses, indicating that cucurbitacin B treatment augmented the effects of radiation in both cell lines where G2/M arrest was observed to occur. However, SKBR-3 did not show to augment the effects of radiation, consistent with the cell cycle distribution shown in Figure 2 and the absence of a G2/M arrest in SKBR-3 cells.

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