In:
Annals of the New York Academy of Sciences, Wiley, Vol. 1095, No. 1 ( 2007-01), p. 7-18
Abstract:
Abstract : Shikonin has been reported to induce apoptosis and inhibit angiogenesis in vivo and in vitro . 6‐(1‐propoxyiminoalkyl)‐5,8‐dimethoxyoxy 1,4‐naphtoquinone S‐64 (DMNQ S‐64) was synthesized as a shikonin derivative. In this article, the underlying apoptotic mechanism of DMNQ S‐64 was examined. DMNQ S‐64 exerted cytotoxicity against A549 lung carcinoma cells with IC 50 of 27.3 μM. Apoptotic bodies were observed in DMNQ S‐64‐treated A549 cells by 4′‐6‐diamidino‐2‐phenylindole (DAPI) staining assay. DMNQ S‐64 also increased sub‐G1 DNA portion in a concentration‐dependent manner by flow cytometric analysis. Western blotting has revealed that DMNQ S‐64 effectively activates the expression of caspase 8, 9, and 3, cleaves poly (ADP‐ribose) polymerase, and increases the ratio of Bax/Bcl‐2. Furthermore, cytochrome c was released in a concentration‐dependent manner by DMNQ S‐64. Similarly, DMNQ S‐64 significantly increased caspase 3 activity by enzyme‐linked immunosorbent assay (ELISA). It also significantly inhibited the level of prostaglandin E2 (PGE 2 ) by ELISA and downregulated the expression of cyclooxygenase‐2 (COX‐2) in a concentration‐dependent manner. Taken together, DMNQ S‐64 may exhibit cytotoxicity against A549 cells via caspase activation and COX‐2 inhibition.
Type of Medium:
Online Resource
ISSN:
0077-8923
,
1749-6632
DOI:
10.1196/annals.1397.002
Language:
English
Publisher:
Wiley
Publication Date:
2007
detail.hit.zdb_id:
2834079-6
detail.hit.zdb_id:
211003-9
detail.hit.zdb_id:
2071584-5
SSG:
11
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