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Isoalantolactone induces intrinsic apoptosis through p53 signaling pathway in human lung squamous carcinoma cells
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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