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Published on: March 30, 2019
Luteolin induced G2 phase cell cycle arrest and apoptosis on non-small cell lung cancer cells
Xueting Cai1, Tingmei Ye, Chao Liu
1School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, Jiangsu, China.
Abstract:
In this study, we investigated the underlying molecular mechanism for the potent cell cycle inhibition and pro-apoptotic effect of luteolin (2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4-chromenone) on human non-small-cell lung carcinoma cell line A549. MTT assay showed that luteolin had obvious cytotoxicity on A549 with IC(50) of 40.2 μM at 48 h. Pro-apoptotic effect of luteolin on A549 cells was demonstrated by Hoechst 33258 staining assay and annexin V-FITC/PI double staining analysis. A great quantity of apoptotic cells and increasing G2 phase cells were observed by flow cytometry. Western blotting assay revealed that luteolin activated JNK, increased Bax, promoted procaspase-9 cleavage and activated caspase-3 at last. Assay using TNFα, an active agent of NF-κB, showed that pretreatment of A549 cells with luteolin could inhibit TNFα induced trans-nuclear of NF-κB. In summary, luteolin displayed a significant cytotoxic effect through cell cycle arrest and apoptosis induction in A549 cells. Pro-apoptotic effect was implemented via activating JNK and inhibiting translocation of NF-κB (p65). These results suggested that luteolin might have therapeutic potential against NSCLC.
Insights
Luteolin effectively inhibits non-small cell lung cancer (NSCLC) by inducing cell cycle arrest and apoptosis. This natural compound activates JNK and blocks NF-κB, showing therapeutic potential for NSCLC treatment.
Area of Science:
- Molecular Biology
- Pharmacology
- Cancer Research
Background:
- Non-small cell lung carcinoma (NSCLC) is a major cause of cancer-related deaths.
- Natural compounds are being investigated for their therapeutic potential against various cancers.
Purpose of the Study:
- To investigate the molecular mechanisms of luteolin's cytotoxic and pro-apoptotic effects on A549 NSCLC cells.
- To explore luteolin's impact on cell cycle regulation and apoptosis pathways.
Main Methods:
- Cytotoxicity assessed by MTT assay.
- Apoptosis evaluated using Hoechst 33258 staining and Annexin V-FITC/PI double staining.
- Cell cycle analysis performed via flow cytometry.
- Protein expression and activation of JNK, Bax, procaspase-9, caspase-3, and NF-κB (p65) analyzed by Western blotting.
Main Results:
- Luteolin exhibited significant cytotoxicity against A549 cells (IC50 = 40.2 μM at 48 h).
- Luteolin induced apoptosis and G2 phase cell cycle arrest in A549 cells.
- Luteolin activated JNK, increased Bax expression, and promoted caspase-3 activation.
- Luteolin inhibited TNFα-induced NF-κB (p65) translocation.
Conclusions:
- Luteolin demonstrates potent anti-cancer activity in NSCLC A549 cells through cell cycle arrest and apoptosis induction.
- The pro-apoptotic effects are mediated by JNK activation and inhibition of NF-κB signaling.
- Luteolin shows promise as a potential therapeutic agent for NSCLC.