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- W2313262088 abstract "Flavonoids and its derivatives are common components found in human diet. Several studies indicated flavonoids could benefit in cancer prevention or therapy, but their structure‐activity relationships (SAR) remain poorly defined. In order to further understand the SAR, a series of oxime‐containing flavone derivatives were designed, synthesized and evaluated for their biological anti‐cancer potential. The anti‐proliferative ability of these compounds was measured by several human cancer cell lines from different origins including nasopharyngeal cancer (NPC‐TW01), leukemia (MT‐2) and lung carcinoma (H661). Among over 30 different oxime‐containing flavone derivatives, ( Z )‐6‐[2‐hydroxyimino‐2‐(4‐methoxyphenyl)ethoxy]‐2‐phenyl ‐4 H ‐1‐ benzopyran‐4‐one (WTC01) possessed potent activity against NPC‐TW01 growth with IC 50 of 400 nM. As determined by flow cytometry, WTC01 treatment results in an accumulation of NPC‐TW01 cells in G 2 ‐M phase following a 6‐h exposure with amaximum accumulation observed by 18 h. Furthermore, Annexin‐V/propidium iodide (PI) binding assay, Hoechst 33258/PI double staining, and PARP cleavage indicates that cell death proceeded through an apoptotic pathway. Interestingly,WTC01 also causes mitochondrial transmembrane potential loss and activation of caspase‐9 and caspase‐3 without noticeable activation of the caspase‐8. These results suggest that the WTC01‐mediated apoptotic signaling pathway depends on the mitochondria and caspase‐9/‐3 cascades. Further studies showed that WTC01 inhibits microtubule assembly in a concentration‐dependent manner, this data suggests that tubulin may serve as the cellular target for WTC01. Taken together, these findings indicated that WTC01, a novel synthetic oxime‐containing flavone, exhibits potent activity against cancer growth through the disruption of microtubule and has potential for management of nasopharyngeal malignancies. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):C236." @default.
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- W2313262088 date "2009-12-10" @default.
- W2313262088 modified "2023-09-27" @default.
- W2313262088 title "Abstract C236: A novel oxime‐containing flavone anticancer agent, WTC01, exhibits potent microtubule disruption ability" @default.
- W2313262088 doi "https://doi.org/10.1158/1535-7163.targ-09-c236" @default.
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