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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

Inhibition of LY294002, following 48 h of treatment with Tan I, and the effect on the phosphorylation of PI3K, Akt and mTOR in breast cancer cells. Tan I, tanshinone I; PI3K, phosphatidylinositide 3-kinase; p-, phosphorylated; Akt, protein kinase B; mTOR, mammalian target of rapamycin.
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f8-mmr-11-02-0931: Inhibition of LY294002, following 48 h of treatment with Tan I, and the effect on the phosphorylation of PI3K, Akt and mTOR in breast cancer cells. Tan I, tanshinone I; PI3K, phosphatidylinositide 3-kinase; p-, phosphorylated; Akt, protein kinase B; mTOR, mammalian target of rapamycin.

Mentions: To further confirm the effects of Tan I on mTOR, LY294002, a specific PI3K inhibitor, was then used. Treatment of breast cancer cells with LY294002 resulted in a reduction in p-Akt and decreased phosphorylation of regulatory PI3K. The levels of p-mTOR were also decreased compared with the untreated controls (Fig. 8). These findings support the hypothesis that the induction of apoptosis in cells by Tan I is mediated by the suppression of PI3K/Akt/mTOR signaling.


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)

Inhibition of LY294002, following 48 h of treatment with Tan I, and the effect on the phosphorylation of PI3K, Akt and mTOR in breast cancer cells. Tan I, tanshinone I; PI3K, phosphatidylinositide 3-kinase; p-, phosphorylated; Akt, protein kinase B; mTOR, mammalian target of rapamycin.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f8-mmr-11-02-0931: Inhibition of LY294002, following 48 h of treatment with Tan I, and the effect on the phosphorylation of PI3K, Akt and mTOR in breast cancer cells. Tan I, tanshinone I; PI3K, phosphatidylinositide 3-kinase; p-, phosphorylated; Akt, protein kinase B; mTOR, mammalian target of rapamycin.
Mentions: To further confirm the effects of Tan I on mTOR, LY294002, a specific PI3K inhibitor, was then used. Treatment of breast cancer cells with LY294002 resulted in a reduction in p-Akt and decreased phosphorylation of regulatory PI3K. The levels of p-mTOR were also decreased compared with the untreated controls (Fig. 8). These findings support the hypothesis that the induction of apoptosis in cells by Tan I is mediated by the suppression of PI3K/Akt/mTOR signaling.

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