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 p53 tumor suppressor gene plays an important role in protecting cells from developing undesirable proliferation. The mutant p53 gene or malfunctioning p53 protein found in more than 50% of cancer cells impedes DNA repair or apoptosis induction. This may be why some cancers gain resistance to chemotherapy and radiation and become more resistant after frequent cancer treatments. A non-toxic p53 gene activator would induce cancer cell apoptosis and help damaged cancer cells to recover. Therefore, the combination use of chemotherapeutics or radiation with a non-toxic p53 gene activator will be crucial in cancer therapy, damaging DNA with chemotherapeutics or radiation on the one hand and promoting apoptosis induction with p53 gene activator on the other. This strategy would be most efficient for remission induction and maintenance in cancer therapy. Antineoplastons are naturally occurring peptides and amino acid derivatives that control neoplastic growth. Antineoplaston A10 and AS2-1 are chemically identified and synthesized antineoplastons proven to inhibit cancer cell growth by arresting the cell cycle in the G1 phase and inhibiting tumor growth by reducing mitosis. These agents are thought to be good candidates for clinically easily applicable non-toxic p53 gene activators. Our cases of advanced cancer responded well to combination treatment using chemotherapeutics and irradiation with antineoplaston A10 and AS2-1 in clinical trials being conducted in Kurume University Hospital. We describe herein the clinical cases and discuss the possible mechanism of action of this combination therapy.
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PMID:A novel strategy for remission induction and maintenance in cancer therapy. 1174 57

Antineoplaston A10 (3-phenylacetylamino-2,6-piperidinedion) is a naturally occurring substance and was the first antineoplaston in the human body to be chemically identified. The effect of antineoplaston A10 on human hepatocellular carcinoma cell lines HepG2 and HLE has been examined. Antineoplaston A10 displayed anti-proliferative action inhibiting cell growth in a dose- and time-dependent manner in vitro as measured by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and clonogenic assays. Incubation with antineoplaston A10 for 48 h induced apoptotic events such as a typical apoptotic morphology, formation of a characteristic ladder pattern of DNA migration and accumulation of sub-G1 phase cells. Next, hepatoma xenografts in nude mice were employed to study the antitumor effects of antineoplaston A10 in vivo. Oral administration of antineoplaston A10 delayed the growth of HepG2 and HLE cells in the mice without a reduction in body weight. A higher proportion of apoptotic cells in xenografts was observed by means of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining. In addition, the level of expression of apoptotic marker p53 increased while that of anti-apoptotic protein bcl-2 decreased, as evaluated with immunohistochemical staining in the xenografts. These results suggested that antineoplaston A10 may inhibit the growth of human hepatoma cells through the induction of apoptosis.
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PMID:Induction of apoptosis in human hepatocellular carcinoma cells by synthetic antineoplaston A10. 1769 34