Back to Search
Start Over
Flavonoids inhibit cell proliferation and induce apoptosis and autophagy through downregulation of PI3Kγ mediated PI3K/AKT/mTOR/p70S6K/ULK signaling pathway in human breast cancer cells
- Source :
- Scientific Reports, Vol 8, Iss 1, Pp 1-13 (2018), Scientific Reports
- Publication Year :
- 2018
- Publisher :
- Springer Science and Business Media LLC, 2018.
-
Abstract
- Anticancer activities of flavonoids derived from Tephroseris kirilowii (Turcz.) Holub. were evaluated in human cancer cells. We isolated and identified, for the first time, eight flavonoids from T. kirilowii and found that three of them (IH: isorhamnetin, GN: genkwanin, and Aca: acacetin) inhibited cell proliferation in a variety of human cancer cell lines. These active flavonoids caused cell cycle arrest at G2/M phase and induced apoptosis and autophagy in human breast cancer cells. Molecular docking revealed that these flavonoids dock in the ATP binding pocket of PI3Kγ. Importantly, treatment with these flavonoids decreased the levels of PI3Kγ-p110, phospho-PI3K, phospho-AKT, phospho-mTOR, phospho-p70S6K, and phospho-ULK. Pretreatment with PI3Kγ specific inhibitor AS605240 potentiated flavonoids-mediated inactivation of AKT, mTOR, p70S6K, ULK, and apoptosis. Taken together, these findings represent a novel mechanism by which downregulation of PI3Kγ-p110 and consequent interruption of PI3K/AKT/mTOR/p70S6K/ULK signaling pathway might play a critical functional role in these flavonoids-induced cell cycle arrest at G2/M phase, apoptosis, and autophagy. Our studies provide novel insights into the anticancer activities of selected flavonoids and their potential uses in anticancer therapy.
- Subjects :
- 0301 basic medicine
Cell cycle checkpoint
Down-Regulation
lcsh:Medicine
Antineoplastic Agents
Apoptosis
Article
03 medical and health sciences
Cell Line, Tumor
Autophagy
Autophagy-Related Protein-1 Homolog
Class Ib Phosphatidylinositol 3-Kinase
Humans
heterocyclic compounds
lcsh:Science
Protein kinase B
PI3K/AKT/mTOR pathway
Cell Proliferation
Phosphoinositide-3 Kinase Inhibitors
Flavonoids
Multidisciplinary
Chemistry
Cell growth
TOR Serine-Threonine Kinases
lcsh:R
fungi
Intracellular Signaling Peptides and Proteins
Ribosomal Protein S6 Kinases, 70-kDa
food and beverages
Oncogene Protein v-akt
030104 developmental biology
Cancer cell
Cancer research
lcsh:Q
Signal transduction
Signal Transduction
Subjects
Details
- ISSN :
- 20452322
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....851c28fc0a57b781ee62ff604992b026