Hemistepsin A induces apoptosis by modulating the reactive oxygen species-dependent PI3K/Akt signaling pathway in human lung carcinoma A549 cells
Hemistepsin A is a sesquiterpene lactone isolated from plants of the family. Recently, this compound was reported to be a bioactive compound that is beneficial for numerous health problems without side effects; however, its effect on lung cancer cells has not yet been studied. Therefore, in this stu...
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Published in | The Korean journal of physiology & pharmacology Vol. 29; no. 5; pp. 625 - 636 |
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Main Author | |
Format | Journal Article |
Language | Korean |
Published |
대한생리학회-대한약리학회
01.09.2025
The Korean Journal of Physiology & Pharmacology Editorial Office |
Subjects | |
Online Access | Get full text |
ISSN | 1226-4512 2093-3827 |
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Summary: | Hemistepsin A is a sesquiterpene lactone isolated from plants of the family. Recently, this compound was reported to be a bioactive compound that is beneficial for numerous health problems without side effects; however, its effect on lung cancer cells has not yet been studied. Therefore, in this study, we investigated the anticancer activity of hemistepsin A in human lung carcinoma A549 cells. This study showed that treatment with hemistepsin A induces apoptosis by activating caspase cascade and reducing the expression of inhibitors of apoptotic protein family members. Additionally, hemistepsin A disrupted mitochondrial integration by altering the levels of Bcl-2 family proteins to increase the cytoplasmic release of cytochrome c. Moreover, hemistepsin A reduced the activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway, and pretreatment with a PI3K inhibitor markedly augmented the cytotoxic effect of hemistepsin A on A549 cells. Furthermore, hemistepsin A significantly enhanced the production of intracellular and mitochondrial reactive oxygen species (ROS), whereas ROS scavengers restored the reduced viability by attenuating DNA damage and apoptosis by blocking the hemistepsin A-mediated inactivation of the PI3K/Akt pathway. Our findings demonstrate that hemistepsin A induces apoptosis in A549 cells by generating ROS, which subsequently inhibits the PI3K/Akt pathway, suggesting that ROS generation is involved as an early inducer of hemistepsin A-mediated anticancer activity. |
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Bibliography: | KISTI1.1003/JNL.JAKO202525254048412 |
ISSN: | 1226-4512 2093-3827 |