RGD Reference Report - Thymoquinone reduces mouse colon tumor cell invasion and inhibits tumor growth in murine colon cancer models. - Rat Genome Database

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Thymoquinone reduces mouse colon tumor cell invasion and inhibits tumor growth in murine colon cancer models.

Authors: Gali-Muhtasib, Hala  Ocker, Matthias  Kuester, Doerthe  Krueger, Sabine  El-Hajj, Zeina  Diestel, Antje  Evert, Matthias  El-Najjar, Nahed  Peters, Brigitte  Jurjus, Abdo  Roessner, Albert  Schneider-Stock, Regine 
Citation: Gali-Muhtasib H, etal., J Cell Mol Med. 2008 Jan-Feb;12(1):330-42. doi: 10.1111/j.1582-4934.2007.00095.x.
RGD ID: 13209144
Pubmed: PMID:18366456   (View Abstract at PubMed)
PMCID: PMC3823493   (View Article at PubMed Central)
DOI: DOI:10.1111/j.1582-4934.2007.00095.x   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CASP3HumanColonic Neoplasms treatmentISOCasp3 (Mus musculus) RGD 
Casp3RatColonic Neoplasms treatmentISOCasp3 (Mus musculus) RGD 
Casp3MouseColonic Neoplasms treatmentIDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Casp3  (caspase 3)

Genes (Mus musculus)
Casp3  (caspase 3)

Genes (Homo sapiens)
CASP3  (caspase 3)


Additional Information