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Effects of combination therapy of docetaxel with selenium on the human breast cancer cell lines MDA-MB-231 and MCF-7.

Park SO, Yoo YB, Kim YH, Baek KJ, Yang JH, Choi PC, Lee JH, Lee KR, Park KS - Ann Surg Treat Res (2015)

Bottom Line: In the MDA-MB-231 cells, the combination therapy group (docetaxel at 500pM plus selenium at 10µM) showed a significantly decreased percentage of cell growth (15% vs. 28%; P = 0.004), a significantly increased percentage of late apoptosis (63% vs. 26%; P = 0.001), and an increased cell cycle arrest in the G2/M phase (P = 0.001) compared with the solitary docetaxel therapy group.Isobologram analysis demonstrated the synergistic effect of the combination therapy in the MDA-MB-231 cells.However, in the MCF-7 cells, no significant differences in the percentage of cell growth apoptosis, the percentage of apoptosis, and the pattern of cell cycle arrest were noted between the combination therapy groups and the solitary docetaxel therapy group.

View Article: PubMed Central - PubMed

Affiliation: Department of Emergency Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea.

ABSTRACT

Purpose: The anticancer property and cytoprotective role of selenium in chemotherapy have been reported. However, the combination effects of selenium on chemotherapy for advanced breast cancer have not yet been clearly defined. The purpose of this study was to investigate the combined effects of selenium on chemotherapy using docetaxel on breast cancer cell lines.

Methods: Under adherent culture conditions, two breast cancer cell lines, MDA-MB-231 and MCF-7, were treated with docetaxel at 500pM and selenium at 100nM, 1µM, or 10µM. Changes in cell growth, cell cycle duration, and degree of apoptosis after 72 hours in each treated group were evaluated.

Results: In the MDA-MB-231 cells, the combination therapy group (docetaxel at 500pM plus selenium at 10µM) showed a significantly decreased percentage of cell growth (15% vs. 28%; P = 0.004), a significantly increased percentage of late apoptosis (63% vs. 26%; P = 0.001), and an increased cell cycle arrest in the G2/M phase (P = 0.001) compared with the solitary docetaxel therapy group. Isobologram analysis demonstrated the synergistic effect of the combination therapy in the MDA-MB-231 cells. However, in the MCF-7 cells, no significant differences in the percentage of cell growth apoptosis, the percentage of apoptosis, and the pattern of cell cycle arrest were noted between the combination therapy groups and the solitary docetaxel therapy group.

Conclusion: Our in vitro study indicated that the combination of selenium with docetaxel inhibits cell proliferation through apoptosis and cell arrest in the G2/M phase in MDA-MB-231 breast cancer cells.

No MeSH data available.


Related in: MedlinePlus

Normalized isobologram for selenium and docetaxel in the MDA-MB-231 (A) and MCF-7 (B) cell lines. Diagonal experimental combination data points, represented by dots located lower left, on the diagonal line, or upper right, indicate synergism, additivity, and antagonism, respectively. Fractional affected-combination index (Fa-CI) plot in combination index analysis in the MDA-MB-231 (C) and MCF-7 (D) cell lines. Combination index values <1, =1, or >1 indicate synergism, additivity, and antagonism, respectively.
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Figure 2: Normalized isobologram for selenium and docetaxel in the MDA-MB-231 (A) and MCF-7 (B) cell lines. Diagonal experimental combination data points, represented by dots located lower left, on the diagonal line, or upper right, indicate synergism, additivity, and antagonism, respectively. Fractional affected-combination index (Fa-CI) plot in combination index analysis in the MDA-MB-231 (C) and MCF-7 (D) cell lines. Combination index values <1, =1, or >1 indicate synergism, additivity, and antagonism, respectively.

Mentions: Normalized isobolograms were constructed for MDA-MB-231 and MCF-7 cells using dose-response curves. In MDA-MB-231 cells, synergism was generally identified when the cells were exposed to 100µM of selenium with docetaxel (Fig. 2). And, an additive effect was generally identified when the cells were exposed to other doses of selenium with docetaxel. In MCF-7 cells, an additive effect was generally identified when the cells were exposed to selenium with docetaxel (Fig. 2).


Effects of combination therapy of docetaxel with selenium on the human breast cancer cell lines MDA-MB-231 and MCF-7.

Park SO, Yoo YB, Kim YH, Baek KJ, Yang JH, Choi PC, Lee JH, Lee KR, Park KS - Ann Surg Treat Res (2015)

Normalized isobologram for selenium and docetaxel in the MDA-MB-231 (A) and MCF-7 (B) cell lines. Diagonal experimental combination data points, represented by dots located lower left, on the diagonal line, or upper right, indicate synergism, additivity, and antagonism, respectively. Fractional affected-combination index (Fa-CI) plot in combination index analysis in the MDA-MB-231 (C) and MCF-7 (D) cell lines. Combination index values <1, =1, or >1 indicate synergism, additivity, and antagonism, respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4325646&req=5

Figure 2: Normalized isobologram for selenium and docetaxel in the MDA-MB-231 (A) and MCF-7 (B) cell lines. Diagonal experimental combination data points, represented by dots located lower left, on the diagonal line, or upper right, indicate synergism, additivity, and antagonism, respectively. Fractional affected-combination index (Fa-CI) plot in combination index analysis in the MDA-MB-231 (C) and MCF-7 (D) cell lines. Combination index values <1, =1, or >1 indicate synergism, additivity, and antagonism, respectively.
Mentions: Normalized isobolograms were constructed for MDA-MB-231 and MCF-7 cells using dose-response curves. In MDA-MB-231 cells, synergism was generally identified when the cells were exposed to 100µM of selenium with docetaxel (Fig. 2). And, an additive effect was generally identified when the cells were exposed to other doses of selenium with docetaxel. In MCF-7 cells, an additive effect was generally identified when the cells were exposed to selenium with docetaxel (Fig. 2).

Bottom Line: In the MDA-MB-231 cells, the combination therapy group (docetaxel at 500pM plus selenium at 10µM) showed a significantly decreased percentage of cell growth (15% vs. 28%; P = 0.004), a significantly increased percentage of late apoptosis (63% vs. 26%; P = 0.001), and an increased cell cycle arrest in the G2/M phase (P = 0.001) compared with the solitary docetaxel therapy group.Isobologram analysis demonstrated the synergistic effect of the combination therapy in the MDA-MB-231 cells.However, in the MCF-7 cells, no significant differences in the percentage of cell growth apoptosis, the percentage of apoptosis, and the pattern of cell cycle arrest were noted between the combination therapy groups and the solitary docetaxel therapy group.

View Article: PubMed Central - PubMed

Affiliation: Department of Emergency Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea.

ABSTRACT

Purpose: The anticancer property and cytoprotective role of selenium in chemotherapy have been reported. However, the combination effects of selenium on chemotherapy for advanced breast cancer have not yet been clearly defined. The purpose of this study was to investigate the combined effects of selenium on chemotherapy using docetaxel on breast cancer cell lines.

Methods: Under adherent culture conditions, two breast cancer cell lines, MDA-MB-231 and MCF-7, were treated with docetaxel at 500pM and selenium at 100nM, 1µM, or 10µM. Changes in cell growth, cell cycle duration, and degree of apoptosis after 72 hours in each treated group were evaluated.

Results: In the MDA-MB-231 cells, the combination therapy group (docetaxel at 500pM plus selenium at 10µM) showed a significantly decreased percentage of cell growth (15% vs. 28%; P = 0.004), a significantly increased percentage of late apoptosis (63% vs. 26%; P = 0.001), and an increased cell cycle arrest in the G2/M phase (P = 0.001) compared with the solitary docetaxel therapy group. Isobologram analysis demonstrated the synergistic effect of the combination therapy in the MDA-MB-231 cells. However, in the MCF-7 cells, no significant differences in the percentage of cell growth apoptosis, the percentage of apoptosis, and the pattern of cell cycle arrest were noted between the combination therapy groups and the solitary docetaxel therapy group.

Conclusion: Our in vitro study indicated that the combination of selenium with docetaxel inhibits cell proliferation through apoptosis and cell arrest in the G2/M phase in MDA-MB-231 breast cancer cells.

No MeSH data available.


Related in: MedlinePlus