Pyrrolidine Dithiocarbamate (PDTC) Attenuates Luteolin-Induced Apoptosis in Human Leukemia HL-60 Cells

Ming-Fen Lee, Cheng-Ta Li, Ming-Dian Chen, An-Chin Cheng

Department of Nutrition and Health Science, Fooyin University, Kaohsiung, Chinese Taipei.
Department of Nutrition and Health Sciences, Chang Jung Christian University, Tainan, Chinese Taipei.

DOI: 10.4236/jct.2012.36147                

Abstract

Studies have indicated that flavonoid luteolin is a potential inhibitor of tumor cell proliferation and may function as an anticarcinogenic agent. Pyrrolidine dithiocarbamate (PDTC), a synthetic compound, may exhibit biphasic effects on apoptosis depending on the experimental context. Previously, we found that luteolin induced the activation of the proapoptotic proteins, such as Bad, Bid, and Bax, in HL-60 human leukemia cells. We also explored the modulatory effects and molecular mechanisms of PDTC on the cytotoxicity of luteolin in HL-60 cells; PDTC could interfere with luteolin’s ability to cleave poly(ADP-ribose)-polymerase (PARP) and DNA fragmentation of factor-45 (DFF-45). In the current study, we further investigated the effect of PDTC on the luteolin-induced death-receptor pathway and the cleavage of the Bcl-2 family members. We found that the combination of luteolin and PDTC increased the survival of the HL-60 cells such that PDTC inhibited both extrinsic and intrinsic pathways in luteolin-induced apoptosis.

Keywords

Apoptosis; Pyrrolidine Dithiocarbamate; HL-60 Cells; Luteolin; Death-Receptor Pathway; Bcl-2 Family

Conflicts of Interest

The authors declare no conflicts of interest.

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