Regulation of the cell cycle and PI3K/Akt/mTOR signaling pathway by tanshinone I in human breast cancer cell lines
Authors: Dawei Sun
Rong Ma
Jianwei Lu
Li Wang
Jinhai Tang
Jianzhong Wu
Journal: Molecular Medicine Reports (2015)
Discipline: CLINICAL MEDICINE
Keywords: Breast cancer; tanshinone I; MCF-7; MDA-MB-453; apoptosis
Affiliations: First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210046, P.R. China., Department of General Surgery, The Affiliated Jiangsu Cancer Hospital, Nanjing Medical University, Nanjing, Jiangsu 210000, P.R. China.

Abstract:  Breast cancer is the second leading cause of cancer‚Äërelated 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‚Äëresponsive MCF‚Ä? and estrogen‚Äëindependent MDA‚ÄëMB‚Ä?53 human breast cancer cells. The cytotoxicity of Tan I was evaluated using a Cell Counting Kit‚Ä? 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‚Äëassociated proteins involved in the phosphatidylinositide 3‚Äëkinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway were detected using western blot analysis using specific protein antibodies. The MCF‚Ä? and MDA‚ÄëMB‚Ä?53 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‚Äëdependent kinase inhibitors p21Cip1 and p27Kip1. In addition, Tan I was found to downregulate anti‚Äëapoptotic 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)‚ÄëPI3K, p‚ÄëAkt and p‚ÄëmTOR. 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. 

Retracted: Yes

PubPeer comments:
 Figure 5.  Morphological changes in the nucleolus of breast cancer cells following treatment with Tan I for 48 h under a fluorescence microscope (magnification, x400) following DNAu2011binding fluorescent dye staining. (Au2011C) MCFu20117 cells and (Du2011F) MDAu2011MBu2011453. Cells undergoing apoptosis and nuclear fragmentation are indicated by arrows.  No nucleoli are visible, and it may be that this should read  nucleus . I am more concerned with the sharp rectangular edges visible around some cells in (B) and (E) at increased contrast (below). , 
 #1 Dear, Thank you very much for kind suggestion. You are right. It is not the nuclei in the Fig. 5C. Herein, it is the plural form of nucleus. Account for the large raw picture, the picture was partially cut, causing a few of cells in the pictures distortion. Iu2019m sorry for our mishandling. In the future research, I will be more serious and responsible for our study. Sincerely , 
 Retracted [12 April 2021] .  Following the publication of the above paper, a concerned reader drew to the Editor s attention that Fig. 5 contained apparent anomalies, including unexpectedly similar-looking cells and repeated patternings of the cells in terms of their layout arrangement within the data panels. After having conducted an independent investigation in the Editorial Office, the Editor of *Molecular Medicine Reports* has determined that the above paper should be retracted from the Journal on account of a lack of confidence regarding the authenticity of the data. The authors were asked for an explanation to account for these concerns, but the Editorial Office never received any reply. The Editor regrets any inconvenience that has been caused to the readership of the Journal. ,