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Published on: March 30, 2019
Silibinin inhibits human nonsmall cell lung cancer cell growth through cell-cycle arrest by modulating expression and
Samiha Mateen1, Alpna Tyagi, Chapla Agarwal
1Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Denver, Aurora, Colorado 80045, USA.
Abstract:
Recent studies show that silibinin possesses a strong antineoplastic potential against many cancers; however, its efficacy and underlying molecular mechanisms in nonsmall cell lung cancer (NSCLC) are not well defined. Herein, we assessed silibinin activity on prime endpoints and key molecular targets such as cell number, cell-cycle progression, and cell-cycle regulatory molecules in three cell lines representing different NSCLC subtypes, namely large cell carcinoma cells (H1299 and H460) and a bronchioalveolar carcinoma cell line (H322). Silibinin treatment (10-75 microM) inhibited cell growth and targeted cell-cycle progressing causing a prominent G(1) arrest in dose- and time-dependent manner. In mechanistic studies, silibinin (50-75 microM) modulated the protein levels of cyclin-dependent kinases (CDKs) (4, 6, and 2), cyclins (D1, D3, and E), CDKIs (p18/INK4C, p21/Cip1, and p27/Kip1) in a differential manner in these three cell lines. Consistent with these observations, silibinin caused a reduction in kinase activity of CDK4 and 2 in all cell lines except no effect on CDK4 kinase activity in H460 cells, and concomitantly reduced Rb phosphorylation. Together, for the first time, these results identify potential molecular targets and anticancer effects of silibinin in NSCLC cells representing different NSCLC subtypes.
Insights
Silibinin, a compound found in milk thistle, effectively inhibits nonsmall cell lung cancer (NSCLC) growth by halting cell-cycle progression. This study identifies key molecular targets, offering new avenues for NSCLC treatment strategies.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Silibinin exhibits antineoplastic properties against various cancers.
- Its specific effects and molecular mechanisms in nonsmall cell lung cancer (NSCLC) require further elucidation.
Purpose of the Study:
- To evaluate the efficacy of silibinin in NSCLC.
- To investigate the molecular mechanisms underlying silibinin's action on NSCLC cell lines.
Main Methods:
- Three NSCLC cell lines (H1299, H460, H322) were treated with varying concentrations of silibinin.
- Cell growth, cell-cycle progression, and levels/activity of cell-cycle regulatory molecules (cyclins, CDKs, CDKIs, Rb) were assessed.
Main Results:
- Silibinin inhibited cell growth and induced a G1 cell-cycle arrest in a dose- and time-dependent manner.
- It differentially modulated the protein levels of key cell-cycle regulators (CDKs, cyclins, CDKIs).
- Silibinin reduced CDK4/2 kinase activity and Rb phosphorylation in most tested NSCLC cell lines.
Conclusions:
- Silibinin demonstrates significant anticancer potential against diverse NSCLC subtypes.
- The study identifies specific molecular targets, including cell-cycle regulatory proteins, for silibinin's action in NSCLC.
- These findings highlight silibinin as a promising agent for NSCLC therapy.
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