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Regulation of the cell cycle and PI3K/Akt/mTOR signaling pathway by tanshinone I in human breast cancer cell lines.

Wang L, Wu J, Lu J, Ma R, Sun D, Tang J - Mol Med Rep (2014)

Bottom Line: Tan I exerted similar antiproliferative activities and induction of apoptosis, resulting in S phase arrest accompanied by decreases in cyclin B and increases in cyclin E and cyclin A proteins, which may have been associated with the upregulation of cyclin‑dependent kinase inhibitors p21Cip1 and p27Kip1.In addition, Tan I was found to downregulate anti‑apoptotic and upregulate associated apoptotic components of the PI3K/Akt/mTOR signaling pathway.These results clearly indicated that the mechanism of action of Tan I involved, at least partially, an effect on the PI3K/Akt/mTOR signaling pathway, providing new information for anticancer drug design and development.

View Article: PubMed Central - PubMed

Affiliation: First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210046, P.R. China.

ABSTRACT
Breast cancer is the second leading cause of cancer‑related mortality in females worldwide. Therefore, identifying alternative strategies to combat the disease mortality is important. The aim of the present study was to investigate the effect of tanshinone I (Tan I) on the tumorigenicity of estrogen‑responsive MCF‑7 and estrogen‑independent MDA‑MB‑453 human breast cancer cells. The cytotoxicity of Tan I was evaluated using a Cell Counting Kit‑8 assay, the apoptosis and cell cycle distribution were detected using flow cytometry and the cell morphology was observed using a fluorescence microscope. In addition, the cell cycle regulatory proteins and apoptosis‑associated proteins involved in the phosphatidylinositide 3‑kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway were detected using western blot analysis using specific protein antibodies. The MCF‑7 and MDA‑MB‑453 cells were equally sensitive to Tan I regardless of their responsiveness to estrogen. Tan I exerted similar antiproliferative activities and induction of apoptosis, resulting in S phase arrest accompanied by decreases in cyclin B and increases in cyclin E and cyclin A proteins, which may have been associated with the upregulation of cyclin‑dependent kinase inhibitors p21Cip1 and p27Kip1. In addition, Tan I was found to downregulate anti‑apoptotic and upregulate associated apoptotic components of the PI3K/Akt/mTOR signaling pathway. Notably, treatment with the PI3K inhibitor, LY294002, decreased the levels of phosphorylated (p)‑PI3K, p‑Akt and p‑mTOR. These results clearly indicated that the mechanism of action of Tan I involved, at least partially, an effect on the PI3K/Akt/mTOR signaling pathway, providing new information for anticancer drug design and development.

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Related in: MedlinePlus

Apoptotic rate of breast cancer cells following treatment with Tan I for 48 h. (A) MCF-7 cells and (B) MDA-MB-453 cells. Tan I, tanshinone I; FITC, fluorescein isothiocyanate; PI, propidium iodide.
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f4-mmr-11-02-0931: Apoptotic rate of breast cancer cells following treatment with Tan I for 48 h. (A) MCF-7 cells and (B) MDA-MB-453 cells. Tan I, tanshinone I; FITC, fluorescein isothiocyanate; PI, propidium iodide.

Mentions: To confirm whether the growth inhibition by Tan I was caused by apoptosis, the percentage of cells undergoing cell apoptosis was determined by calculating the number of cells in early and late apoptosis. Following exposure to various concentrations of Tan I for 48 h, the percentage of Annexin V-positive cells increased from 14.80±3.34% to 30.13±4.26% in the MCF-7 cells, with significant differences compared with the control (7.78±2.34%; P<0.05; Fig. 4A). A relatively smaller effect was observed in the MDA-MB-453 cells (Fig. 4B).


Regulation of the cell cycle and PI3K/Akt/mTOR signaling pathway by tanshinone I in human breast cancer cell lines.

Wang L, Wu J, Lu J, Ma R, Sun D, Tang J - Mol Med Rep (2014)

Apoptotic rate of breast cancer cells following treatment with Tan I for 48 h. (A) MCF-7 cells and (B) MDA-MB-453 cells. Tan I, tanshinone I; FITC, fluorescein isothiocyanate; PI, propidium iodide.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4262478&req=5

f4-mmr-11-02-0931: Apoptotic rate of breast cancer cells following treatment with Tan I for 48 h. (A) MCF-7 cells and (B) MDA-MB-453 cells. Tan I, tanshinone I; FITC, fluorescein isothiocyanate; PI, propidium iodide.
Mentions: To confirm whether the growth inhibition by Tan I was caused by apoptosis, the percentage of cells undergoing cell apoptosis was determined by calculating the number of cells in early and late apoptosis. Following exposure to various concentrations of Tan I for 48 h, the percentage of Annexin V-positive cells increased from 14.80±3.34% to 30.13±4.26% in the MCF-7 cells, with significant differences compared with the control (7.78±2.34%; P<0.05; Fig. 4A). A relatively smaller effect was observed in the MDA-MB-453 cells (Fig. 4B).

Bottom Line: Tan I exerted similar antiproliferative activities and induction of apoptosis, resulting in S phase arrest accompanied by decreases in cyclin B and increases in cyclin E and cyclin A proteins, which may have been associated with the upregulation of cyclin‑dependent kinase inhibitors p21Cip1 and p27Kip1.In addition, Tan I was found to downregulate anti‑apoptotic and upregulate associated apoptotic components of the PI3K/Akt/mTOR signaling pathway.These results clearly indicated that the mechanism of action of Tan I involved, at least partially, an effect on the PI3K/Akt/mTOR signaling pathway, providing new information for anticancer drug design and development.

View Article: PubMed Central - PubMed

Affiliation: First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210046, P.R. China.

ABSTRACT
Breast cancer is the second leading cause of cancer‑related mortality in females worldwide. Therefore, identifying alternative strategies to combat the disease mortality is important. The aim of the present study was to investigate the effect of tanshinone I (Tan I) on the tumorigenicity of estrogen‑responsive MCF‑7 and estrogen‑independent MDA‑MB‑453 human breast cancer cells. The cytotoxicity of Tan I was evaluated using a Cell Counting Kit‑8 assay, the apoptosis and cell cycle distribution were detected using flow cytometry and the cell morphology was observed using a fluorescence microscope. In addition, the cell cycle regulatory proteins and apoptosis‑associated proteins involved in the phosphatidylinositide 3‑kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway were detected using western blot analysis using specific protein antibodies. The MCF‑7 and MDA‑MB‑453 cells were equally sensitive to Tan I regardless of their responsiveness to estrogen. Tan I exerted similar antiproliferative activities and induction of apoptosis, resulting in S phase arrest accompanied by decreases in cyclin B and increases in cyclin E and cyclin A proteins, which may have been associated with the upregulation of cyclin‑dependent kinase inhibitors p21Cip1 and p27Kip1. In addition, Tan I was found to downregulate anti‑apoptotic and upregulate associated apoptotic components of the PI3K/Akt/mTOR signaling pathway. Notably, treatment with the PI3K inhibitor, LY294002, decreased the levels of phosphorylated (p)‑PI3K, p‑Akt and p‑mTOR. These results clearly indicated that the mechanism of action of Tan I involved, at least partially, an effect on the PI3K/Akt/mTOR signaling pathway, providing new information for anticancer drug design and development.

Show MeSH
Related in: MedlinePlus