Isoalantolactone induces intrinsic apoptosis through p53 signaling pathway in human lung squamous carcinoma cells
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Published on: June 9, 2023
Chengyan Jin1, Guangxin Zhang1, Yifan Zhang1
1Jilin Provincial Key Laboratory on Molecular and Chemical Genetic, The Second Hospital of Jilin University, Changchun, P.R. China.
Abstract:
Isoalantolactone has recently been revealed to induce apoptosis in several types of cancer. However, little is reported on its anti-tumor potential on human lung cancer. Our present study was designed to investigate its effects on human lung squamous carcinoma SK-MES-1 cells. We found that Isoalantolactone induced cellular and DNA morphological changes and decreased the viability of SK-MES-1 cells. It significantly inhibited the growth of SK-MES-1 cells through apoptosis in a dose-dependent manner via activation of p53. It also induced cell cycle arrest at G1 phase. It can down-regulate Bcl-2 and up-regulate Bax, to induce dissipation of mitochondrial membrane potential and generation of reactive oxygen species. Caspase-3 was also activated by Isoalantolactone, with the cleavage of poly (ADP-ribose) polymerase. Our results reveal that Isoalantolactone induces intrinsic apoptosis in SK-MES-1 cells through p53 signaling pathway, which suggests that Isoalantolactone could be a potential leading compound for future development of anti-lung cancer drugs.
Insights
Isoalantolactone triggers apoptosis in human lung squamous carcinoma cells by activating p53. This natural compound shows potential as a novel anti-lung cancer therapeutic agent.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Isoalantolactone demonstrates apoptosis-inducing properties in various cancer types.
- Limited research exists on its efficacy against human lung cancer.
Purpose of the Study:
- To investigate the anti-tumor effects of Isoalantolactone on human lung squamous carcinoma SK-MES-1 cells.
- To elucidate the underlying molecular mechanisms of its action.
Main Methods:
- Cell viability assays to assess SK-MES-1 cell growth.
- Apoptosis induction analysis, including DNA fragmentation and morphological changes.
- Western blotting to examine key protein expressions (p53, Bcl-2, Bax, Caspase-3, PARP).
- Mitochondrial membrane potential and reactive oxygen species (ROS) generation assays.
- Cell cycle analysis.
Main Results:
- Isoalantolactone significantly reduced SK-MES-1 cell viability in a dose-dependent manner.
- The compound induced characteristic apoptotic morphological and DNA changes.
- Isoalantolactone activated the p53 signaling pathway, leading to G1 phase cell cycle arrest.
- Down-regulation of Bcl-2 and up-regulation of Bax were observed, alongside mitochondrial dysfunction and ROS generation.
- Activation of Caspase-3 and cleavage of PARP confirmed apoptosis induction.
Conclusions:
- Isoalantolactone effectively induces intrinsic apoptosis in human lung squamous carcinoma SK-MES-1 cells via the p53 signaling pathway.
- These findings highlight Isoalantolactone as a promising candidate for developing new anti-lung cancer therapies.
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