Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The identification of agents that preferentially kill cancer cells while protecting normal cells offers the potential to overcome toxicities found in many existing chemotherapeutic agents. Because p53 is frequently inactivated in cancer, agents that preferentially kill p53-null cells and protect wild-type p53-expressing cells are highly desirable chemotherapeutic agents. By using pairs of isogenic colon cancer cell lines that differ only in p53 expression (RKO and HCT116), securinine was found to exhibit these properties. Securinine (30 microM) induces apoptosis in 73% of p53-null HCT116 cells (LD(50) 17.5 microM) as opposed to 17.6% of HCT116 parental cells (LD(50) 50 microM) at 72 h after treatment. The mechanism of securinine-mediated death in p53-deficient cells involves the induction of the p53 family member, p73. Interestingly, the proapoptotic protein p73 is down-regulated in colon cancer cells expressing p53. This differential regulation of p73 in a p53-dependent fashion reveals a novel pathway for preferentially targeting cancer cells. In contrast to p53-deficient cells, cells expressing p53 are protected from cell death through the p53-mediated up-regulation of p21. These studies reveal a novel approach to specifically target colon cancer cells lacking p53 as well as identify a novel clinically relevant pathway to selectively induce p73 in p53-null cells.
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PMID:Securinine induces p73-dependent apoptosis preferentially in p53-deficient colon cancer cells. 2013 3

Natural products have been discovered to be valuable sources of antitumor drugs. L-Securinine is a natural product extracted from the leaves or roots of Securinega suffruticosa Pall Rehd. The current study was done to investigate the molecular mechanisms of antitumor effects of L-securinine. The inhibitory activities of L-securinine on human breast cancer MCF-7 cells were studied in vitro by a Cell Counting Kit-8(cck8) assay. Flow cytometry was used to analyze the apoptotic ratio and cell cycle distribution of control and treated MCF-7 cells with L-Securinine. Real-time quantitative PCR was conducted to evaluate expression levels of apoptosis related genes P53, Bax, Bcl-2, Mtor, P70s6k. L-Securinine exhibited remarkable antiproliferation activities on MCF-7 cells in dose- and time-dependent manner (24, 48 and 72 h of incubation). A 48 h exposure to L-securinine at a concentration ranging from 0 to 40 microM resulted in a significant increase in apoptotic ratio. At both low and high concentrations, L-securinine preferably perturbed the cell cycle in MCF-7 cells by arrest of G1 phase. These results were further confirmed by the increased expression of bax, p53 and the decreased expression of bcl-2, mtor, p70s6k in a dose-dependent manner. In summary, these findings suggest that L-securinine has an anti-tumor effect against MCF-7 cells and could be further exploited as a potential lead in antitumor drug development.
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PMID:Antiproliferative activity and apoptosis-inducing mechanism of L-securinine on human breast cancer MCF-7 cells. 2471 13