Silybin suppresses cell proliferation and induces apoptosis of multiple myeloma cells via the PI3K/Akt/mTOR signaling pathway
- 10 February 2016
- journal article
- Published by Spandidos Publications in Molecular Medicine Reports
- Vol. 13 (4), 3243-3248
- https://doi.org/10.3892/mmr.2016.4887
Abstract
Silybin is a biologically active component extracted from the seeds of Silybum marianum, which has been shown to have inhibitory effects on prostate, skin, bladder, lung and colon cancer cells, in addition to its efficacy in the treatment of liver diseases, including hepatitis and cirrhosis. The aim of the present study was to investigate whether silybin suppresses the proliferation and induces apoptosis of multiple myeloma (MM) cells and to elucidate its molecular targets. The proliferative and apoptotic rates of the U266 MM cell line were assessed using MTT and flow‑cytometric assays, respectively. Western blot analysis was used to assess the protein levels of phosphoinositide‑3 kinase (PI3K), phosphorylated (p)‑Akt and p‑mammalian target of rapamycin (mTOR) in U266 cells. In addition, PI3K inhibitor LY294002 or activator insulin‑like growth factor 1 were used to investigate the involvement of the PI3K/Akt‑mTOR signaling pathway in the effect of silybin on U266 cells. The results revealed that silybin restrained the proliferation and enhanced the apoptosis of U266 cells. Furthermore, silybin inhibited the protein expression of PI3K, p‑Akt and p‑mTOR in U266 cells. Of note, inhibition of PI3K facilitated silybin‑mediated reduction of mTOR activation, cell proliferation and induction of apoptosis in U266 cells, while activation of PI3K attenuated the effects of silybin. In conclusion, silybin suppressed cell proliferation and promoted apoptosis of U266 cells via PI3K/Akt-mTOR signaling pathways.Keywords
This publication has 23 references indexed in Scilit:
- Isoegomaketone induces apoptosis in SK-MEL-2 human melanoma cells through mitochondrial apoptotic pathway via activating the PI3K/Akt pathwayInternational Journal of Oncology, 2014
- Clinical experience with plerixafor as a mobilization regimen for autologous peripheral blood stem cell transplantation in patients with refractory germ cell tumorsMolecular and Clinical Oncology, 2014
- Rosiglitazone suppresses angiogenesis in multiple myeloma via downregulation of hypoxia-inducible factor-1α and insulin-like growth factor-1 mRNA expressionMolecular Medicine Reports, 2014
- The natural flavonoid silybin improves the response to Photodynamic Therapy of bladder cancer cellsJournal of Photochemistry and Photobiology B: Biology, 2014
- A novel approach for the efficient extraction of silybin from milk thistle fruitsPharmacognosy Magazine, 2014
- Silybin-Mediated Inhibition of Notch Signaling Exerts Antitumor Activity in Human Hepatocellular Carcinoma CellsPLOS ONE, 2013
- Multiple myeloma with extramedullary plasmacytoma invading the skin and eyeballs following autologous stem cell transplantation: A case reportExperimental and Therapeutic Medicine, 2013
- Anti-Cancer Efficacy of Silybin Derivatives - A Structure-Activity RelationshipPLOS ONE, 2013
- Effects of gambogic acid on the activation of caspase-3 and downregulation of SIRT1 in RPMI-8226 multiple myeloma cells via the accumulation of ROSOncology Letters, 2012
- Discovery of chrysoeriol, a PI3K-AKT-mTOR pathway inhibitor with potent antitumor activity against human multiple myeloma cells in vitroJournal of Huazhong University of Science and Technology [Medical Sciences], 2010