Abstract | BACKGROUND: METHODS: RESULTS: We found that when As4S4 was combined with JQ1, cisplatin, irinotecan or celecoxib, its cytotoxic activity was dramatically enhanced in both gastric and colon cancer cell lines. As4S4 and JQ1 inhibited BRD4 and c-Myc while activating p53 expression synergistically. As4S4 inhibited COX2 and cyclin D1 expression. When As4S4 was combined with chemotherapy drug cisplatin or COX2 inhibitor celecoxib, its inhibition of COX2, BCL2, and p38 expression was enhanced. As4S4 and cisplatin synergistically stimulated p53, phosphor-p38 (p-p38), and increased cleaved caspase 3 (c-caspase 3). CONCLUSION: As4S4 in combination with JQ1, cisplatin, irinotecan or celecoxib showed enhanced cytotoxic effect on gastric and colon cancer cells, indicating the potential application of these novel drug combinations as part of treatment strategy that warrants further investigation. As4S4 and JQ1 demonstrate synergistic activation of p53 and inhibition of c-Myc. As4S4 and cisplatin and celecoxib activated multiple apoptosis pathways.
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Authors | Lian Zhang, Yingying Tong, Xiuli Zhang, Minggui Pan, Siyu Chen |
Journal | Drug design, development and therapy
(Drug Des Devel Ther)
Vol. 9
Pg. 5851-62
( 2015)
ISSN: 1177-8881 [Electronic] New Zealand |
PMID | 26586936
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- (+)-JQ1 compound
- Arsenicals
- Azepines
- Sulfides
- Triazoles
- Tumor Suppressor Protein p53
- arsenic trisulfide
- Irinotecan
- p38 Mitogen-Activated Protein Kinases
- Celecoxib
- Cisplatin
- Camptothecin
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Topics |
- Antineoplastic Combined Chemotherapy Protocols
(administration & dosage, pharmacology)
- Apoptosis
(drug effects)
- Arsenicals
(administration & dosage)
- Azepines
(administration & dosage)
- Camptothecin
(administration & dosage, analogs & derivatives)
- Celecoxib
(administration & dosage)
- Cell Line, Tumor
- Cisplatin
(administration & dosage)
- Colonic Neoplasms
(drug therapy, pathology)
- Drug Synergism
- Gene Expression Regulation, Neoplastic
(drug effects)
- Humans
- Irinotecan
- Stomach Neoplasms
(drug therapy, pathology)
- Sulfides
(administration & dosage)
- Triazoles
(administration & dosage)
- Tumor Suppressor Protein p53
(metabolism)
- p38 Mitogen-Activated Protein Kinases
(genetics)
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