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Phenethyl isothiocyanate as a potential chemopreventive agent mediates apoptosis and growth arrest in human lung cancer cells
Jen Wei Chiao, Qi Wang, Jie Chen, Wei Dai, C. Clifford Conaway, Yang Ming Yang, Ram Kancherla, T. Ahmed, Fung-Lung Chung
New York Medical College, Valhalla, NY.
There is growing evidence that isothiocyanates from cruciferous vegetables are effective chemopreventive agents for cancers including tobacco carcinogen-induced lung tumors in mice.
Dietary feeding of phenethyl isothiocyanate (PEITC) has been demonstrated recently to inhibit lung tumorigenesis in benzo(a)pyrene treated A/J mice during the course of post-initiation, offering a possible approach to the prevention of lung cancer in ex-smokers.
The mechanism and effects of PEITC on human lung cancer cells however remain to be fully described. A human lung cancer cell line A549 was exposed to PEITC from 0.1-100 µM. The effects of PEITC, examined at different time points, revealed a time-dependent induction of the expression of Bax gene. An early increase could be detected within 4 hours; the endogenous substrate PARP was degraded in parallel and the caspases also activated.
The level of Bax was decreased subsequently, prior to the detection of apoptotic cells with DNA strand breaks after 20-24 hours. The number of apoptotic cells was dose-related to PEITC. PEITC also induced a retardation of cell cycle progression, observed within 24 h-exposure to PEITC (20 µM), simultaneously with the early events of apoptosis. The entry of cells at G1 cell cycle into replicating ph
ases S and G2M was reduced, indicating a G1 block. The magnitude of the reduction was time-dependent.
The results indicated that PEITC regulates the expression of mediators for cellular proliferation and apoptosis in human lung cancer cells in a similar way as in mouse lung. PEITC may be effective chemopreventive as well as therapeutic agents for human lung cancer.
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