JuBei Oral Liquid Induces Mitochondria-Mediated Apoptosis in NSCLC Cells
Zhenzhen Pan1, Qiufang Chen2, Xiulan Zheng1
1Department of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, People's Republic of China.
Background:
Although gefitinib brings about tremendous advances in the treatment of non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations, most of patients become incurable due to drug resistance. JuBei oral liquid (JB) has been widely used to treat pneumonia in clinic. Components of JB were reported to induce apoptosis in NSCLC, which indicated that JB could be a potential antitumor agent for NSCLC patients. In this study, we investigated the effect of JB on gefitinib-sensitive PC-9 and gefitinib-resistant PC-9/GR, H1975 cells as well as its underlying molecular mechanisms.
Methods:
PC-9, PC-9/GR and H1975 cells were treated with JB, LY294002, SCH772984, gefitinib alone or in combination. Then, cell viability, colony formation, cell death, expression of mitochondria-dependent pathway proteins, expression of EGFR, PI3K/AKT, MAPK signal pathway proteins, Bcl-2 mitochondrial translocation, ROS generation and cell apoptosis were examined by MTT, colony forming, live/dead cell staining, Western blot, immunofluorescence and flow cytometry assay.
Results:
Our results showed that JB significantly induced cell growth inhibition and apoptotic cell death in PC-9, PC-9/GR and H1975 cells. JB activated mitochondria-mediated apoptotic pathway through inhibiting Bcl-2 mitochondrial translocation while inducing Bax translocated into mitochondria along with accumulated ROS production, thereby increasing the release of cytochrome c, subsequently cleaving procaspase9 into cleaved-caspase9 and then cleaving procaspase3 into cleaved-caspase3. Furthermore, the employment of protein kinase inhibitors LY294002 and SCH772984 revealed that the induction of mitochondria-mediated apoptosis by JB was reliant on inactivation of PI3K/AKT and MAPK signal pathways. Moreover, JB could synergize with gefitinib to induce apoptosis in PC-9, PC-9/GR and H1975 cells.
Conclusion:
These data indicated that JB could be a potential therapeutic agent for NSCLC patients harboring EGFR mutations as well as those under gefitinib resistance.
Insights
JuBei oral liquid (JB) effectively inhibits non-small cell lung cancer (NSCLC) cell growth and induces apoptosis, offering a potential treatment for both gefitinib-sensitive and resistant EGFR-mutated NSCLC.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Gefitinib resistance is a major challenge in treating EGFR-mutated non-small cell lung cancer (NSCLC).
- JuBei oral liquid (JB), traditionally used for pneumonia, has shown potential in inducing apoptosis in NSCLC cells.
Purpose of the Study:
- To investigate the efficacy of JB on gefitinib-sensitive (PC-9) and gefitinib-resistant (PC-9/GR, H1975) NSCLC cells.
- To elucidate the molecular mechanisms underlying JB's anti-cancer effects.
Main Methods:
- Cells were treated with JB alone or in combination with gefitinib, LY294002, or SCH772984.
- Assays included cell viability, colony formation, cell death, Western blot, immunofluorescence, and flow cytometry to assess apoptosis and signaling pathways.
Main Results:
- JB significantly inhibited cell growth and induced apoptosis in all tested NSCLC cell lines.
- JB activated the mitochondria-mediated apoptotic pathway by modulating Bcl-2, Bax, ROS, and cytochrome c release.
- JB's pro-apoptotic effects were dependent on the inactivation of PI3K/AKT and MAPK signaling pathways.
- JB synergized with gefitinib to enhance apoptosis in NSCLC cells.
Conclusions:
- JB demonstrates significant anti-cancer activity against gefitinib-sensitive and resistant NSCLC.
- JB represents a promising therapeutic agent for NSCLC patients with EGFR mutations, including those who have developed gefitinib resistance.
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