Abstract
Purpose: Pendulone, an isoflavone compound, is known to act against human cancer cells. However, its role in human non-small cell lung cancer (NSCLC) and the exact molecular mechanisms of action have never been reported. Methods: We investigated the effects of pendulone on cell proliferation and apoptosis in human NSCLC H1299 cells. Cell viability was examined using the methyl-thiazol-diphenyl-tetrazolium (MTT) assay. Flow cytometry was employed to evaluate apoptotic indices such as the cell cycle, mitochondrial membrane potential, cytochrome c release, caspase activity, and death receptor expression. The expression of proteins related to the cell cycle and apoptosis were analyzed by Western blot analysis. Results: Pendulone significantly decreased H1299 cell viability by inducing endoplasmic reticulum (ER) stress through the accumulation of reactive oxygen species (ROS). Pendulone induced the expression of ER stress-associated proteins, such as ATF4 and CHOP, which promoted the expression of death receptors. Activation of caspase 8 induced extrinsic pathway apoptosis. Pendulone also caused the loss of mitochondrial membrane potential, inhibited the anti-apoptotic proteins BCL-2 and activated the pro-apoptotic protein BAX, which promoted the release of cytochrome c to activate caspase 9. Antioxidant N-acetylcysteine (NAC), with its ROS-suppressive property, reversed pendulone-induced ER stress and cell apoptosis. Conclusion: Our findings provide evidence that pendulone induces apoptosis by inducing ER stress through ROS accumulation and mitochondrial dysfunction in NSCLC cell lines.
Original language | English |
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Article number | 105346 |
Journal | Toxicology in Vitro |
Volume | 81 |
DOIs | |
Publication status | Published - Jun 2022 |
Keywords
- Apoptosis
- Endoplasmic reticulum (ER)
- Non-small cell lung cancer (NSCLC)
- Pendulone
- Reactive oxygen species (ROS)
ASJC Scopus subject areas
- Toxicology