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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

Effects of Tan I treatment for 48 h on the cell cycle distribution of breast cancer cells. (A) MCF-7 cells and (B) MDA-MB-453 cells. Tan I, tanshinone I.
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f3-mmr-11-02-0931: Effects of Tan I treatment for 48 h on the cell cycle distribution of breast cancer cells. (A) MCF-7 cells and (B) MDA-MB-453 cells. Tan I, tanshinone I.

Mentions: As regulation of the cell cycle is important in the growth and development of cancer, the effect of Tan I on cell cycle progression was determined using FCM over a 48-h period. The results of the cell cycle analysis revealed that Tan I significantly induced a dose-dependent S phase (P<0.01) with a corresponding decrease in the G0/G1 and G2/M phase fractions. A modest increase was observed in the percentage of MCF-7 cells in the S phase, from 39.42±3.53 to 51.54±5.71% (P<0.01), following exposure to Tan I for 48 h (Fig. 3A). Similarly, compared with the control group, Tan I increased the population of MDA-MB-453 cells in the S phase; 40.34±3.81, 57.46±5.52 and 65.56±6.13, for RPMI-1640 media (control), 2.5 μg/ml Tan I and 5 μg/ml Tan I (Fig. 3B), respectively, which was accompanied by a reduced population of cells in the G0/G1 phase. These results suggested that the inhibition of breast cancer cell viability by Tan I may be associated with a dose-dependent shift of cell distribution into the S phase.


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)

Effects of Tan I treatment for 48 h on the cell cycle distribution of breast cancer cells. (A) MCF-7 cells and (B) MDA-MB-453 cells. Tan I, tanshinone I.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f3-mmr-11-02-0931: Effects of Tan I treatment for 48 h on the cell cycle distribution of breast cancer cells. (A) MCF-7 cells and (B) MDA-MB-453 cells. Tan I, tanshinone I.
Mentions: As regulation of the cell cycle is important in the growth and development of cancer, the effect of Tan I on cell cycle progression was determined using FCM over a 48-h period. The results of the cell cycle analysis revealed that Tan I significantly induced a dose-dependent S phase (P<0.01) with a corresponding decrease in the G0/G1 and G2/M phase fractions. A modest increase was observed in the percentage of MCF-7 cells in the S phase, from 39.42±3.53 to 51.54±5.71% (P<0.01), following exposure to Tan I for 48 h (Fig. 3A). Similarly, compared with the control group, Tan I increased the population of MDA-MB-453 cells in the S phase; 40.34±3.81, 57.46±5.52 and 65.56±6.13, for RPMI-1640 media (control), 2.5 μg/ml Tan I and 5 μg/ml Tan I (Fig. 3B), respectively, which was accompanied by a reduced population of cells in the G0/G1 phase. These results suggested that the inhibition of breast cancer cell viability by Tan I may be associated with a dose-dependent shift of cell distribution into the S phase.

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