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A Stilbenoid Isorhapontigenin as a Potential Anti-Cancer Agent against Breast Cancer through Inhibiting Sphingosine Kinases/Tubulin Stabilization
- Source :
- Cancers, Volume 11, Issue 12
- Publication Year :
- 2019
- Publisher :
- MDPI AG, 2019.
-
Abstract
- Isorhapontigenin (ISO), a tetrahydroxylated stilbenoid, is an analog of resveratrol (Rsv). The various biological activities of Rsv and its derivatives have been previously reported in the context of both cancer and inflammation. However, the anti-cancer effect of ISO against breast cancer has not been well established, despite being an orally bioavailable dietary polyphenol. In this study, we determine the anti-cancer effects of ISO against breast cancer using MCF7, T47D, and MDA-MB-231 cell lines. We observed that ISO induces breast cancer cell death, cell cycle arrest, oxidative stress, and the inhibition of cell proliferation. Additionally, sphingosine kinase inhibition by ISO controlled tubulin polymerization and cancer cell growth by regulating MAPK/PI3K-mediated cell cycle arrest in MCF7 cells. Interestingly, SPHK1/2 gene silencing increased oxidative stress, cell death, and tubulin destabilization in MCF7 cells. This suggests that the anti-cancer effect of ISO can be regulated by SPHK/tubulin destabilization pathways. Overall, ISO successfully induced breast cancer cell death and cell growth arrest, suggesting this phytochemical is a better alternative for breast cancer treatment. Further studies in animal models could confirm the potency and usability of ISO over Rsv for targeting breast cancer, potentially posing an alternative candidate for improved therapy in the near future.
- Subjects :
- 0301 basic medicine
Cancer Research
Cell cycle checkpoint
proliferation
Isorhapontigenin
Sphingosine kinase
SPHK2
SPHK1
Article
03 medical and health sciences
chemistry.chemical_compound
breast cancer
0302 clinical medicine
Breast cancer
medicine
skin and connective tissue diseases
Cell growth
apoptosis
Cancer
medicine.disease
tubulin destabilization
030104 developmental biology
Oncology
chemistry
030220 oncology & carcinogenesis
Cancer cell
Cancer research
isorhapontigenin
Subjects
Details
- ISSN :
- 20726694
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Cancers
- Accession number :
- edsair.doi.dedup.....2c944ab3d5b658ab0b53f9c0cdf71d2b