The relationship between statins and breast cancer prognosis varies by statin type and exposure time: a meta-analysis

Liu, Binliang; Yi, Zongbi; Guan, Xiuwen; Zeng, Yi Xin

doi:10.1007/s10549-017-4246-0

Cited by 95 publications

(78 citation statements)

References 29 publications

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“…Breast cancer (BC) is the most common cancer in females and the leading cause of death worldwide, which are clinically heterogeneous. Because of heterogeneous, clinically BC may be respond poorly to neoadjuvant chemotherapy, or it is respond well to endocrine therapy .…”

Section: Discussionmentioning

confidence: 99%

A novel role of kynureninase in the growth control of breast cancer cells and its relationships with breast cancer

Liu

Feng

Lai

et al. 2019

J Cellular Molecular Medi

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Breast cancer is the most common malignancy among women worldwide. Kynureninase (KYNU) located in 2q22.2, which was associated with tryptophan utilization and metabolic diseases including cardiac, renal and limb defects syndrome 2. However, the role of KYNU in breast cancer (BC) development remains unclear. The expression of KYNU was examined by immunohistochemistry (IHC) in 137 primary BC tissues, and the correlation of KYNU expression with clinical pathological characteristics and the biomarkers (ER, PR, HER2, E‐cad and Ki‐67) was analysed. The role of KYNU in cancer cell proliferation, tumour growth and development was evaluated by MTT assay, soft agar colony formation assay and xenograft mouse models. Among 137 primary BC tissues, 46.7% (64/137) had high KYNU expression (IHC scores >4) while 53.3% (73/137) had low KYNU expression (IHC scores ≤4). The expression of KYNU was positively correlated with the expressions of ER (P = .002), PR (P = .007) and E‐cad (P = .03), while negatively associated with tumour grade (P = .008), tumour stage (P < .001) and the expressions of HER2 (P = .04) and Ki‐67 (P = .019). Overexpression of KYNU significantly inhibited cell proliferation in cell culture, colony formation in soft agar and xenograft BC development in NOD/SCID mice. Kynureninase suppresses BC cell proliferation, tumour growth and development. Kynureninase may function as a tumour suppressor in BC.

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Section: Discussionmentioning

confidence: 99%

A novel role of kynureninase in the growth control of breast cancer cells and its relationships with breast cancer

Liu

Feng

Lai

et al. 2019

J Cellular Molecular Medi

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“…20,31 Statins may also target histone deacetylases (HDACs) to alter protein acetylation status to reduce cell proliferation and in vivo tumour growth. 33,34 Kotamraju et al 35 reported that statins activate arginase-dependent pathways to cause cell death in breast cancer cells. Recent studies demonstrated that stains usage reduces breast cancer-specific mortality in patients with breast cancer.…”

Section: Introductionmentioning

confidence: 99%

Lovastatin‐mediated MCF‐7 cancer cell death involves LKB1‐AMPK‐p38MAPK‐p53‐survivin signalling cascade

Huang

Chyuan

Shiue

et al. 2019

J Cellular Molecular Medi

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There is increasing evidence that statins, which are widely used in lowering serum cholesterol and the incidence of cardiovascular diseases, also exhibits anti-tumour properties. The underlying mechanisms by which statins-induced cancer cell death, however, remain incompletely understood. In this study, we explored the anti-tumour mechanisms of a lipophilic statin, lovastatin, in MCF-7 breast cancer cells. Lovastatin inhibited cell proliferation and induced cell apoptosis. Lovastatin caused p21 elevation while reduced cyclin D1 and survivin levels. Lovastatin also increased p53 phosphorylation, acetylation and its reporter activities. Results from chromatin immunoprecipitation analysis showed that p53 binding to the survivin promoter region was increased, while Sp1 binding to the region was decreased, in MCF-7 cells after lovastatin exposure. These actions were associated with liver kinase B1 (LKB1), AMP-activated protein kinase (AMPK) and p38 mitogen-activated protein kinase (p38MAPK) activation. Lovastatin's enhancing effects on p53 activation, p21 elevation and survivin reduction were significantly reduced in the presence of p38MAPK signalling inhibitor. Furthermore, LKB1-AMPK signalling blockade abrogated lovastatin-induced p38MAPK and p53 phosphorylation. Together these results suggest that lovastatin may activate LKB1-AMPK-p38MAPK-p53-survivin cascade to cause MCF-7 cell death. The present study establishes, at least in part, the signalling cascade by which lovastatin induces breast cancer cell death. K E Y W O R D Sbreast cancer, liver kinase B1, lovastatin, p53, surviving Huang and Chyuan contributed equally to this work. | 1823HUANG et Al.

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“…Therefore, the investigation of pleiotropic effects sometimes reveals novel applications of clinically proven medicines. Besides some minor discrepancies, several cohort studies or clinical trials showed accumulating evidence of the clinical benefits of statins for breast cancer patients, via nonlipid‐lowering therapeutic effects, aka pleiotropic effects . The involvement of glucose‐ and cholesterol‐rich diets in the metabolic reprogramming of cells and the augmentation of the oncogenic process have also been reported .…”

Section: Introductionmentioning

confidence: 99%

Lipophilic statins antagonistically alter the major epithelial‐to‐mesenchymal transition signaling pathways in breast cancer stem–like cells via inhibition of the mevalonate pathway

Koohestanimobarhan

Salami

Imeni

et al. 2018

J of Cellular Biochemistry

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Resistance to therapies, recurrence, and metastasis remain challenging issues for breast cancer patients, particularly for triple-negative and breast cancer stem cells. The activation of the epithelial-to-mesenchymal transition (EMT) plays an indispensable role in the poor prognosis of those types. The accumulating proofs indicated that the mevalonate pathway crucially mediates a poor prognosis. Here, the effects of lipophilic 3-hydroxy-3-methyl-glutaryl-coenzyme A inhibitors, atorvastatin, lovastatin, and simvastatin, were investigated on expression and function of a selected profile of EMT-related genes in breast cancer stem-like cells. A nontoxic dose of statins (5 μM for 4 days) significantly (P < 0.05 and >2-fold change) altered expression of 50 of 71 studied genes with a shared cluster of 37 genes that are coding chief operator of signaling pathways in Hippo, Notch, Wnt, proliferation, invasion, angiogenesis, and cell death. They also significantly decreased the levels of Yap/Taz proteins and shifted the expression of vimentin/E-cadherin in favor of induction of differentiation. Statins significantly chemosensitized the treated cells to doxorubicin and also reduced in vitro migration of the cells. Whereas lovastatin and simvastatin significantly decreased the expression of CD44, atorvastatin drastically increased CD24 and caused more wide-ranging impacts. In summary, the statins hold back the process of EMT by the antagonizing of EMT-promoting pathways. High degree of overlapping findings is supportive of the central role of the mevalonate pathway in cancer stem-like cells, but further studies are required to find the optimized chemical structure for the maximum abrogation of orchestrated EMT pathways.

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The relationship between statins and breast cancer prognosis varies by statin type and exposure time: a meta-analysis

Cited by 95 publications

References 29 publications

A novel role of kynureninase in the growth control of breast cancer cells and its relationships with breast cancer

A novel role of kynureninase in the growth control of breast cancer cells and its relationships with breast cancer

Lovastatin‐mediated MCF‐7 cancer cell death involves LKB1‐AMPK‐p38MAPK‐p53‐survivin signalling cascade

Lipophilic statins antagonistically alter the major epithelial‐to‐mesenchymal transition signaling pathways in breast cancer stem–like cells via inhibition of the mevalonate pathway

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