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Am. J. Biomed. Sci. 2015, 7(3), 190-197; doi: 10.5099/aj150300190
Received: 2 July 2015; | Revised: 17 September 2015; | Accepted: 24 September 2015


Chemosenstizing Effects of a Novel Anti-inflammatory Small Molecule, UTL-5g, and Its Analogs


B. Chen1, W-H. Huang2, A-R. Lee2, J. Media3, F. Valeriote3, J. Shaw1,*

1 21st Century Therapeutics, Inc., Detroit, Michigan 48202

2 National Defense Medical Center, Taipei, Taiwan

3 Henry Ford Health Systems, Detroit, Michigan 48202

*Corresponding author

Jiajiu Shaw, Ph.D.

21st Century Therapeutic, Inc.

440 Burroughs St., Suite 447

Detroit, Michigan 48202


E-mail: jiajiushaw@gmail.com

Phone (734) 330-6052



Our previous studies showed that UTL-5g, a novel anti-inflammatory TNF-α inhibitor, enhanced the chemotherapeutic efficacy of cisplatin against HCT-15 human colon cancer cells in an animal tumor model. To extend the study, we set out to investigate 3 newly synthesized analogs of UTL-5g (UTLOH-4a, -4b, and -4c) on whether they are associated with similar biological effects. Chemosensitizing effects of UTL-5g and its 3 analogs were investigated using HCT-15 cells in vitro with increasing doses of cisplatin, carboplatin, or oxaliplatin. IC50 of each drug was determined from the dose-response surviving curves. The anti-inflammatory effects were examined by their ability to inhibit PGE2 production in mouse RAW cells stimulated with LPS. Myelotoxicity induced by cisplatin was examined with human CFU-GM clonogenic assay. All 4 compounds significantly potentiated the cytotoxic effect of cisplatin against HCT-15 cancer cells by lowering the IC50 values. Among them, UTL-5g appeared to be the most promising sensitizer of cisplatin and UTLOH-4b was the most potent sensitizer of carboplatin. Anti-inflammatory study showed that UTL-5g, UTLOH-4a, and -4c inhibited PGE2 production in LPS-stimulated RAW cells. In addition, UTL-5g and UTLOH-4a enhanced the survival of CFU-GM colony counts in cultures containing cisplatin, carboplatin and oxaliplatin respectively.

Keywords: chemosensitizer, cisplatin, HCT-15, CFU-GM, UTL-5g, PGE2.

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