WMJ‐8‐B, a novel hydroxamate derivative, induces MDA‐MB‐231 breast cancer cell death <i>via</i> the SHP‐1‐STAT3‐survivin cascade

Chuang, Yu Fan; Huang, Shihping Kevin; Hsu, Ya Fen; Yu, Meng; Ou, George; Huang, Wei; Hsu, Ming Jen

doi:10.1111/bph.13929

Cited by 16 publications

(44 citation statements)

References 72 publications

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“…13 We noted in this study that lovastatin caused We showed that lovastatin activates LKB1-AMPK-p38MAPK signalling pathway, leading to p53 phosphorylation. 13 We noted in this study that lovastatin caused We showed that lovastatin activates LKB1-AMPK-p38MAPK signalling pathway, leading to p53 phosphorylation.…”

Section: Discussionmentioning

confidence: 74%

“…13 The RT-PCR was then conducted following the manufacturer's instructions (Super Script On-Step RT-PCR system, Invitrogen). 13 The RT-PCR was then conducted following the manufacturer's instructions (Super Script On-Step RT-PCR system, Invitrogen).…”

Section: Reverse-transcription Polymerase Chain Reaction (Rt-pcr)mentioning

confidence: 99%

“…13 For LKB1 suppression, pre-designed siRNA targeting the human LKB1 or negative control siRNA was purchased from Sigma-Aldrich (St Louis, MO, USA). 13 For LKB1 suppression, pre-designed siRNA targeting the human LKB1 or negative control siRNA was purchased from Sigma-Aldrich (St Louis, MO, USA).…”

Section: Suppression Of Lkb1 Expressionmentioning

confidence: 99%

“…13,14,20,42 We thus determined whether lovastatin modulates the expression of these proteins in MCF-7 cells. In addition, survivin reduction causes cell cycle arrest and death in a variety of cancer cells.…”

Section: Lovastatin Caused P21 Elevation and Survivin Reduction In mentioning

confidence: 99%

“…[8][9][10] Moriai et al 11 recently showed that targeting survivin may overcome tamoxifen resistance in breast cancer cells. Many transcription factors such as specificity protein 1 (Sp1), 12 signal transducer and activator of transcription 3 (STAT3) 13 and hypoxia-inducible factor-1α (HIF-1α) contribute to survivin induction. 8 Survivin expression is mainly regulated at the level of transcription.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 74%

Section: Reverse-transcription Polymerase Chain Reaction (Rt-pcr)mentioning

confidence: 99%