Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.36 (caspase-1)
 6,285 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

High-dose vitamin C administration has been reported to exhibit antitumor effect in various mouse models of cancer. However, the underlying mechanism of antitumor effect against colorectal cancer remains to be elucidated. In this study, we investigated the antitumor effect of high-dose vitamin C in a mouse model of chronic inflammation-associated colorectal cancer induced by azoxymethane (AOM) and dextran sodium sulfate (DSS). After cancer induction, the mice were administered vitamin C and/or irinotecan. Because irinotecan is a key drug in colorectal cancer treatment, it was used for comparison in this study. We examined reactive oxygen species (ROS) and interleukin-6 (IL-6) levels in the plasma of mice, as well as collagen type I and caspase-1 expression and neutrophil and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL)-positive cell counts in the colon tissue. Vitamin C and/or irinotecan administration decreased the plasma level of ROS and IL-6 and increased the expression of collagen type I and caspase-1. Furthermore, it increased neutrophil and TUNEL-positive cell counts. The most significant changes in the parameters analyzed were observed when both vitamin C and irinotecan were administered.
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PMID:Administration of High-Dose Vitamin C and Irinotecan Ameliorates Colorectal Cancer Induced by Azoxymethane and Dextran Sodium Sulfate in Mice. 3050 81

Arsenic trioxide (ATO) is an effective therapeutic agent against acute promyelocytic leukemia (APL); however, its anti-tumor effect on solid tumors such as colorectal cancer (CRC) is still in debate. Ascorbic acid (AA) also produces a selective cytotoxic activity against tumor cells. Here, we exploit the potential benefit of ATO/AA combination in generating cytotoxicity to CRC cells, which may lay the groundwork for the potential combinational chemotherapy of CRCs. According to the results, we found that ATO and AA effectively inhibited the viability of human CRC cells in a synergistic manner. AA and ATO corporately activated caspase-3 to trigger apoptosis and upregulated the expression of caspase-1 and promoted formation of inflammasomes to induce pyroptosis. Furthermore, the stimulation of reactive oxygen species (ROS) overproduction was demonstrated as a subcellular mechanism for apoptosis and pyroptosis induced by ATO/AA combination treatment. Our findings suggest that ATO combination with a conventional dosage of AA offers an advantage for killing CRC cells. The synergistic action of ATO/AA combination might be considered a plausible strategy for the treatment of CRC and perhaps other solid tumors as well.
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PMID:Ascorbic Acid Sensitizes Colorectal Carcinoma to the Cytotoxicity of Arsenic Trioxide via Promoting Reactive Oxygen Species-Dependent Apoptosis and Pyroptosis. 3215 15