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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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Antiproliferative activity of tanshinone I on breast cancer cells over several time periods. (A) MCF-7 cells and (B) MDA-MB-453 cells. *P<0.01, #P<0.01 and *P<0.05, compared with the control.
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f2-mmr-11-02-0931: Antiproliferative activity of tanshinone I on breast cancer cells over several time periods. (A) MCF-7 cells and (B) MDA-MB-453 cells. *P<0.01, #P<0.01 and *P<0.05, compared with the control.

Mentions: A CCK8 assay was used to elucidate the potential biological effects of Tan I on MCF-7 and MDA-MB-453 breast cancer cells. As shown in Fig. 2A, the MCF-7 cells treated with Tan I exhibited a significant reduction in proliferation rate as the dose concentration and incubation duration increased, compared with the control cells (P<0.05). Notably, similar antiproliferative activities of Tan I on were detected in the MDA-MB-453 cells in a dose- and time-dependent manner. (P<0.05; Fig. 2B). These results implied that Tan I is important in the growth control of breast cancer cells.


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)

Antiproliferative activity of tanshinone I on breast cancer cells over several time periods. (A) MCF-7 cells and (B) MDA-MB-453 cells. *P<0.01, #P<0.01 and *P<0.05, compared with the control.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2-mmr-11-02-0931: Antiproliferative activity of tanshinone I on breast cancer cells over several time periods. (A) MCF-7 cells and (B) MDA-MB-453 cells. *P<0.01, #P<0.01 and *P<0.05, compared with the control.
Mentions: A CCK8 assay was used to elucidate the potential biological effects of Tan I on MCF-7 and MDA-MB-453 breast cancer cells. As shown in Fig. 2A, the MCF-7 cells treated with Tan I exhibited a significant reduction in proliferation rate as the dose concentration and incubation duration increased, compared with the control cells (P<0.05). Notably, similar antiproliferative activities of Tan I on were detected in the MDA-MB-453 cells in a dose- and time-dependent manner. (P<0.05; Fig. 2B). These results implied that Tan I is important in the growth control of breast cancer cells.

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