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Diallyl sulfide induces cell cycle arrest and apoptosis in HeLa human cervical cancer cells through the p53, caspase- and mitochondria-dependent pathways.
Int J Oncol. 2011 Jun; 38(6):1605-13.IJ

Abstract

Diallyl sulfide (DAS), one of the main active constituents of garlic, causes growth inhibition of cancer cells in vitro and promotes immune responses in vivo in experimental settings. However, its effects on the induction of cell cycle and apoptosis in human cervical cancer cells are still unclear. The aims of this study were to explore the anti-cancer effects of DAS in HeLa human cervical cancer cells and to investigate the underlying mechanisms in vitro. Cytotoxicity and apoptosis in HeLa human cervical cancer cells were examined by the morphological changes, viability assay, 4',6-Diamidino-2-phenylindole dihydrochloride (DAPI) staining, comet assay, Western blotting and confocal microscopy examination. The results showed that DAS treatment for 24-72 h resulted in a marked decrease in cell viability time- and dose-dependently. Flow cytometric analysis showed that a 48-h treatment of 75 µM DAS induced G0/G1 cell cycle arrest and sub-G1 phase (apoptosis) in HeLa cells. Typical apoptotic nucleus alterations were observed by fluorescence microscopy in HeLa cells after exposure to DAS using DAPI staining. Cells treated with different concentrations of DAS also showed changes typical of apoptosis such as morphological changes, DNA damage and fragmentation, dysfunction of mitochondria, cytochrome c release and increased expression of pro-caspase-3 and -9. DAS also promoted the release of AIF and Endo G from mitochondria in HeLa cells. In conclusion, DAS induced G0/G1 cell cycle arrest and apoptosis in HeLa cells through caspase- and mitochondria and p53 pathways providing further understanding of the molecular mechanisms of DAS action in cervical cancer. This study, therefore, revealed that DAS significantly inhibits the growth and induces apoptosis of human cervical cancer HeLa cells in vitro.

Authors+Show Affiliations

School of Pharmacy, China Medical University, Taichung 404, Taiwan, ROC.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21424116

Citation

Wu, Ping-Ping, et al. "Diallyl Sulfide Induces Cell Cycle Arrest and Apoptosis in HeLa Human Cervical Cancer Cells Through the P53, Caspase- and Mitochondria-dependent Pathways." International Journal of Oncology, vol. 38, no. 6, 2011, pp. 1605-13.
Wu PP, Chung HW, Liu KC, et al. Diallyl sulfide induces cell cycle arrest and apoptosis in HeLa human cervical cancer cells through the p53, caspase- and mitochondria-dependent pathways. Int J Oncol. 2011;38(6):1605-13.
Wu, P. P., Chung, H. W., Liu, K. C., Wu, R. S., Yang, J. S., Tang, N. Y., Lo, C., Hsia, T. C., Yu, C. C., Chueh, F. S., Lin, S. S., & Chung, J. G. (2011). Diallyl sulfide induces cell cycle arrest and apoptosis in HeLa human cervical cancer cells through the p53, caspase- and mitochondria-dependent pathways. International Journal of Oncology, 38(6), 1605-13. https://doi.org/10.3892/ijo.2011.973
Wu PP, et al. Diallyl Sulfide Induces Cell Cycle Arrest and Apoptosis in HeLa Human Cervical Cancer Cells Through the P53, Caspase- and Mitochondria-dependent Pathways. Int J Oncol. 2011;38(6):1605-13. PubMed PMID: 21424116.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Diallyl sulfide induces cell cycle arrest and apoptosis in HeLa human cervical cancer cells through the p53, caspase- and mitochondria-dependent pathways. AU - Wu,Ping-Ping, AU - Chung,Hui-Wen, AU - Liu,Kuo-Ching, AU - Wu,Rick Sai-Chuen, AU - Yang,Jai-Sing, AU - Tang,Nou-Ying, AU - Lo,Chyi, AU - Hsia,Te-Chun, AU - Yu,Chien-Chih, AU - Chueh,Fu-Shin, AU - Lin,Song-Shei, AU - Chung,Jing-Gung, Y1 - 2011/03/17/ PY - 2010/12/29/received PY - 2011/02/21/accepted PY - 2011/3/23/entrez PY - 2011/3/23/pubmed PY - 2011/8/10/medline SP - 1605 EP - 13 JF - International journal of oncology JO - Int. J. Oncol. VL - 38 IS - 6 N2 - Diallyl sulfide (DAS), one of the main active constituents of garlic, causes growth inhibition of cancer cells in vitro and promotes immune responses in vivo in experimental settings. However, its effects on the induction of cell cycle and apoptosis in human cervical cancer cells are still unclear. The aims of this study were to explore the anti-cancer effects of DAS in HeLa human cervical cancer cells and to investigate the underlying mechanisms in vitro. Cytotoxicity and apoptosis in HeLa human cervical cancer cells were examined by the morphological changes, viability assay, 4',6-Diamidino-2-phenylindole dihydrochloride (DAPI) staining, comet assay, Western blotting and confocal microscopy examination. The results showed that DAS treatment for 24-72 h resulted in a marked decrease in cell viability time- and dose-dependently. Flow cytometric analysis showed that a 48-h treatment of 75 µM DAS induced G0/G1 cell cycle arrest and sub-G1 phase (apoptosis) in HeLa cells. Typical apoptotic nucleus alterations were observed by fluorescence microscopy in HeLa cells after exposure to DAS using DAPI staining. Cells treated with different concentrations of DAS also showed changes typical of apoptosis such as morphological changes, DNA damage and fragmentation, dysfunction of mitochondria, cytochrome c release and increased expression of pro-caspase-3 and -9. DAS also promoted the release of AIF and Endo G from mitochondria in HeLa cells. In conclusion, DAS induced G0/G1 cell cycle arrest and apoptosis in HeLa cells through caspase- and mitochondria and p53 pathways providing further understanding of the molecular mechanisms of DAS action in cervical cancer. This study, therefore, revealed that DAS significantly inhibits the growth and induces apoptosis of human cervical cancer HeLa cells in vitro. SN - 1791-2423 UR - https://www.unboundmedicine.com/medline/citation/21424116/Diallyl_sulfide_induces_cell_cycle_arrest_and_apoptosis_in_HeLa_human_cervical_cancer_cells_through_the_p53_caspase__and_mitochondria_dependent_pathways_ L2 - http://www.spandidos-publications.com/ijo/38/6/1605 DB - PRIME DP - Unbound Medicine ER -