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Thymoquinone reduces mouse colon tumor cell invasion and inhibits tumor growth in
murine colon cancer models
#MMPMID18366456
Gali-Muhtasib H
; Ocker M
; Kuester D
; Krueger S
; El-Hajj Z
; Diestel A
; Evert M
; El-Najjar N
; Peters B
; Jurjus A
; Roessner A
; Schneider-Stock R
J Cell Mol Med
2008[Jan]; 12
(1
): 330-42
PMID18366456
show ga
We have shown that thymoquinone (TQ) is a potent antitumor agent in human
colorectal cancer cells. In this study, we evaluated TQ's therapeutic potential
in two different mice colon cancer models [1,2-dimethyl hydrazine (DMH) and
xenografts]. We also examined TQ effects on the growth of C26 mouse colorectal
carcinoma spheroids and assessed tumor invasion in vitro. Mice were treated with
saline, TQ, DMH, or combinations once per week for 30 weeks and the multiplicity,
size and distribution of aberrant crypt foci (ACF) and tumors were determined at
weeks 10, 20 and 30. TQ injected intraperitoneally (i.p.) significantly reduced
the numbers and sizes of ACF at week 10; ACF numbers were reduced by 86%. Tumor
multiplicity was reduced at week 20 from 17.8 in the DMH group to 4.2 in mice
injected with TQ. This suppression was observed at week 30 and was long-term;
tumors did not re-grow even when TQ injection was discontinued for 10 weeks. In a
xenograft model of HCT116 colon cancer cells, TQ significantly (P < 0.05) delayed
the growth of the tumor cells. Using a matrigel artificial basement membrane
invasion assay, we demonstrated that sub-cyto-toxic doses of TQ (40 microM)
decreased C26 cell invasion by 50% and suppressed growth in three-dimensional
spheroids. Apoptotic signs seen morphologically were increased significantly in
TQ-treated spheroids. TUNEL staining of xenografts and immunostaining for caspase
3 cleavage in DMH tumors confirmed increased apoptosis in mouse tumors in
response to TQ. These data should encourage further in vivo testing and support
the potential use of TQ as a therapeutic agent in human colorectal cancer.
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