Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bavachinin is a flavanone obtained from the Chinese herb, Fructus Psoraleae. Flavonoids and flavanones are recognized as cancer preventive agents. We investigated the anticancer properties of bavachinin using a model of dimethylhydrazine (DMH and dextran sodium sulfate (DSS) induced rat colon cancer. We investigated aberrant crypt foci (ACF), hyperplastic lesions, catalase (CAT), superoxide dismutase (SOD) and glutathione (GST) levels in Wistar rats. Expression of cancer biomarkers including IL-6, p53, Bcl2 and BAX was investigated. We found that bavachinin administered to rats re-established the colonic crypts that were damaged by DMH and prevented progression of the cancer.
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PMID:Bavachinin mitigates DMH induced colon cancer in rats by altering p53/Bcl2/BAX signaling associated with apoptosis. 3266 69

The Ras/RAF/MEK/ERK pathway is an essential signaling cascade for various refractory cancers, such as those with mutant KRAS (mKRAS) and BRAF (mBRAF). However, there are unsolved ambiguities underlying mechanisms for this growth signaling thereby creating therapeutic complications. This study shows that a vital component of the pathway CRAF is directly impacted by an end product of the cascade, glutathione transferases (GST) P1 (GSTP1), driving a previously unrecognized autocrine cycle that sustains proliferation of mKRAS and mBRAF cancer cells, independent of oncogenic stimuli. The CRAF interaction with GSTP1 occurs at its N-terminal regulatory domain, CR1 motif, resulting in its stabilization, enhanced dimerization, and augmented catalytic activity. Consistent with the autocrine cycle scheme, silencing GSTP1 brought about significant suppression of proliferation of mKRAS and mBRAF cells in vitro and suppressed tumorigenesis of the xenografted mKRAS tumor in vivo. GSTP1 knockout mice showed significantly impaired carcinogenesis of mKRAS colon cancer. Consequently, hindering the autocrine loop by targeting CRAF/GSTP1 interactions should provide innovative therapeutic modalities for these cancers.
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PMID:A CRAF/glutathione-S-transferase P1 complex sustains autocrine growth of cancers with KRAS and BRAF mutations. 3271 31


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