LG308, a Novel Synthetic Compound with Antimicrotubule Activity in Prostate Cancer Cells, Exerts Effective Antitumor Activity
The Journal of Pharmacology and Experimental Therapeutics, ISSN: 0022-3565, Vol: 355, Issue: 3, Page: 473-483
2015
- 8Citations
- 17Captures
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Example: if you select the 1-year option for an article published in 2019 and a metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019. If you select the 3-year option for the same article published in 2019 and the metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019, 2018 and 2017.
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Metrics Details
- Citations8
- Citation Indexes8
- CrossRef8
- Captures17
- Readers17
- 17
Article Description
Microtubule plays many different essential roles in the process of tumorigenesis in many eukaryotes, and targeting mitotic progression by disturbing microtubule dynamics is used as a common strategy for cancer treatment. Microtubule-targeted drugs, including paclitaxel and Vinca alkaloids, were previously considered to work primarily by increasing or decreasing the cellular microtubule mass. The tubulin/microtubule system, which is an integral component of the cytoskeleton, is a therapeutic target for prostate cancer. In this study, we found a novel synthetic compound, 8-fluoro- N -phenylacetyl-1, 3, 4, 9-tetrahydro- β -carboline (LG308), which disrupted the microtubule organization via inhibiting the polymerization of microtubule in PC-3M and LNCaP prostate cancer cell lines. Further study proved that LG308 induced mitotic phase arrest and inhibited G2/M progression significantly in LNCaP and PC-3M cell lines in a dose-dependent manner, and these were associated with the upregulation of cyclin B1 and mitotic marker MPM-2 and the dephosphorylation of cdc2. Besides, the cell proliferation and colony formation of PC-3M and LNCaP cells were effectively inhibited by LG308. Furthermore, LG308 induced apoptosis and cell death in PC-3M and LNCaP cell lines in vitro. In vivo, LG308 dramatically suppressed the growth and metastasis of prostate cancer in both xenograft and orthotopic models. All these data indicate that LG308 is a promising anticancer candidate with antimitotic activity for the treatment of prostate cancer.
Bibliographic Details
http://www.sciencedirect.com/science/article/pii/S0022356524191793; http://dx.doi.org/10.1124/jpet.115.225912; http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84966421063&origin=inward; http://www.ncbi.nlm.nih.gov/pubmed/26377911; https://linkinghub.elsevier.com/retrieve/pii/S0022356524191793; https://dx.doi.org/10.1124/jpet.115.225912; https://jpet.aspetjournals.org/content/355/3/473
Elsevier BV
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