Combination of diethyldithiocarbamate with 12-O-tetradecanoyl phorbol-13-acetate inhibits the growth of human myeloid leukemia HL-60 cells in vitro and in xenograft model.

Abstract

12-O-tetradecanoylphorbol-13-acetate (TPA), is a major active constituent of the seed oil of Croton tiglium L., has pharmacological activity for the treatment of acute myeloid leukemia patients. Diethyldithiocarbamate (DTC) is a potent inhibitor of NF-κB show activity of anticancer. In this study, we determined the effect of DTC and TPA in combination on HL-60 cells cultured in vitro and in vivo. In this study, we have shown that DTC and TPA synergistically inhibited the growth of HL-60 cells and strongly induced apoptosis in the cells. Mechanistic studies showed that the combined effects of DTC and TPA were associated with a decrease in Bcl-2. The animal experiment showed that the combination of DTC and TPA more potently inhibited the growth of HL-60 tumors than either agent alone. Our results indicate that the administration of TPA and DTC in combination may be an effective strategy for inhibiting the growth of acute myeloid leukemia cells.

• Authors: Yuran Ma, Shaohua Chen, Min Chen, Xiang Ren, Nandini Patel, Wenfeng Liu, Huarong Huang, Renping Zhou, Kun Zhang, Susan Goodin, Dongli Li, Xi Zheng
• Journal: Bioscience, biotechnology, and biochemistry (Biosci Biotechnol Biochem) Vol. 84 Issue 10 Pg. 2069-2076 (Oct 2020) ISSN: 1347-6947 [Electronic] England
• PMID: 32640883 (Publication Type: Journal Article)

Chemical References

• Proto-Oncogene Proteins c-bcl-2
• Ditiocarb
• Tetradecanoylphorbol Acetate

Topics

• Animals
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Ditiocarb (pharmacology)
• Drug Synergism
• Humans
• Leukemia, Myeloid (pathology)
• Male
• Mice
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Tetradecanoylphorbol Acetate (pharmacology)
• Xenograft Model Antitumor Assays