期刊
NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL
卷 65, 期 4, 页码 611-622出版社
ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
DOI: 10.1080/01635581.2013.776090
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资金
- DST
- UGC
- UGC (RFSMS)
- Department of Science and Technology, Govt. of India [SR/SO/BB-58/2007]
- University Grant Commission [UGC-37-398/2009]
- UGC-DSA
Diallyl disulfide (DADS), the major organosulfur component of processed garlic is very effective in chemoprevention of several types of cancers; however, its detailed mechanism is yet to be divulged. Present study shows antiproliferative activity of DADS against human leukemic cell-lines, mainly U937. DADS induced transient G2/M phase arrest, which is evident from FACS analysis. The results revealed that a significant transcriptional induction of p21 happened in early hours of treatment, which is due to increased nuclear translocation of NF-B and its specific binding to p21 promoter. However, in the later hours, G2/M arrest is lost leading to apoptosis via intrinsic mitochondria-mediated pathway through generation of reactive oxygen species followed by changes in mitochondrial membrane potential. Western blots indicate release of cytochrome-c, activation of caspase-3, cleavage of PARP1, and finally decrease in bcl-2 levels. In addition, inactivation of NF-B by its inhibitor BAY 11-7085 causes early onset of apoptosis without any transient G2/M arrest. Thus, in conclusion, DADS induces reversible G2/M arrest through NF-B mediated pathway in human leukemic cell lines, like U937, K562, and Jurkat, lacking wild type p53. However, G2/M arrest is lost owing to the incapability of the damage repair system that leads to apoptosis.
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