Casticin inhibits breast cancer cell migration and invasion by down-regulation of PI3K/Akt signaling pathway
Authors: Yingping Xu
Guangrong Huang
Hui Zhu
Baolan Gong
Qiuhong Zhou
Yi Zhang
Jieyu Lü
Ying Liu
Guijuan Zhu
Li Fan
Journal: Bioscience Reports (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Breast cancer; Casticin; MMP-9; PI3K/Akt; invasion.
Affiliations: Department of Obstetrics and Gynecology, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China., Department of Obstetrics and Gynecology, Zhuxi Maternal and Child Health Hospital, Shiyan 442000, Hubei Province, China., Department of Gynecology, Shenzhen Bao'an Traditional Chinese Medicine Hospital Group, Shenzhen 518133, Guangdong Province, China .

Abstract:  Casticin is one of the major active components isolated from Fructus viticis Increasing studies have revealed that casticin has potential anticancer activity in various cancer cells, but its effects on breast cancer cell migration and invasion are still not well known. Therefore, the ability of cell migration and invasion in the breast cancer MDA-MB-231 and 4T1 cells treated by casticin was investigated. The results indicated that casticin significantly inhibited cell migration and invasion in the cells exposed to 0.25 and 0.50 µM of casticin for 24 h. Casticin treatment reduced matrix metalloproteinase (MMP) 9 (MMP-9) activity and down-regulated MMP-9 mRNA and protein expression, but not MMP-2. Casticin treatment suppressed the nuclear translocation of transcription factors c-Jun and c-Fos, but not nuclear factor-κB (NF-κB), and decreased the phosphorylated level of Akt (p-Akt). Additionally, the transfection of Akt overexpression vector to MDA-MB-231 and 4T1 cells could up-regulate MMP-9 expression concomitantly with a marked increase in cell invasion, but casticin treatment reduced Akt, p-Akt, and MMP-9 protein levels and inhibited the ability of cell invasion in breast cancer cells. Additionally, casticin attenuated lung metastasis of mouse 4T1 breast cancer cells in the mice and down-regulated MMP-9 expression in the lung tissues of mice treated by casticin. These findings suggest that MMP-9 expression suppression by casticin may act through inhibition of the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway, which in turn results in the inhibitory effects of casticin on cell migration and invasion in breast cancer cells. Therefore, casticin may have potential for use in the treatment of breast cancer invasion and metastasis. 

Retracted: No

PubPeer comments:
 Fig 3.  (B) representative image of the cell viability assay after cell transfection with miR-885-5p mimic and inhibitor. ... The relative expression levels of epithelial-mesenchymal transition-related proteins (N-cadherin, E-cadherin, vimentin and Snail) after cell transfection assayed by ... (D) western blot analysis ![file] Fig 5.  (B) representative image of the Transwell migration assay on the effects of miR-885-5p suppression combined with SOCS suppression in colorectal cancer cells. ... The relative expression levels of N-cadherin, E-cadherin, vimentin and Snail after miR-885-5p suppression combined with SOCS suppression assayed by... (D) western blot analysis . ![file] Transwell images like blurry leopard-spot fabric, with repeated regions. WBs like rows of little sledges. These are familiar from the  Tadpole papermill . E.g. Fig 3D from [Cao et al (2018)] . ![file] Fig 4D and 6C D from [Wang et al (2018)] . ![] Plagiarising a comment by Elisabeth Bik: ----------------------------------------- This paper belongs to a set of over 400 papers (as per February 2020) that share very similar Western blots with tadpole-like shaped bands, the same background pattern, and striking similarities in title structures, paper layout, bar graph design, and - in a subset - flow cytometry panels. Despite these similarities, these papers are authored by researchers from different departments and institutes, with almost no overlap in authors. The list of these papers is available here: https: docs.google.com spreadsheets d 1KXqTAyl4j-jVorFPMD2XRpr76LcIKJ0CVyIvRj0exYQ edit?usp=sharing A more detailed description of this set of papers, suspected to all be generated by a common source, a paper mill , can be found here: - https: forbetterscience.com 2020 01 24 the-full-service-paper-mill-and-its-chinese-customers (January 2020) - https: scienceintegritydigest.com 2020 02 21 the-tadpole-paper-mill (February 2020) The same paper mill has been described in these papers: - Jana Christopher - Systematic fabrication of scientific images revealed - FEBS Letters (2018) - https: febs.onlinelibrary.wiley.com doi full 10.1002 1873-3468.13201 - Jennifer A Byrne and Jana Christopher - Digital magic, or the dark arts of the 21st centuryu2014how can journals and peer reviewers detect manuscripts and publications from paper mills? - FEBS Letters (2020) - https: febs.onlinelibrary.wiley.com doi full 10.1002 1873-3468.13747 ,