Phenethyl isothiocyanate inhibits growth of human chronic myeloid leukemia K562 cells via reactive oxygen species generation and caspases

Abstract

Abstract. Phenethyl isothiocyanate (PEITC), a potential cancer chemopreventive constituent of cruciferous vegetables, including watercress, has been reported to inhibit cancer cell growth by arresting the cell cycle and inducing apoptosis in various human cancer cell models. However, the role of PEITC in the inhibition of human chronic myeloid leukemia (CML) K562 cell growth and its underlying mechanisms have yet to be elucidated. In the present study, PEITC was found to induce cell death through the induction of reactive oxygen species (ROS) stress and oxidative damage. Heme oxygenase-1 (HO-1), which participates in the development of numerous tumors and the sensitivity of these tumors to chemotherapeutic drugs, plays a protective role by modulating oxidative injury. Therefore, the present study assessed the inhibitory effect of PEITC on K562 cells and whether HO-1 facilitated cell apoptosis and ROS generation. PEITC was found to suppress cell growth and cause apoptosis by promoting Fas and Fas ligand expression, increasing ROS generation and by the successive release of cytochrome c as well as the activation of caspase-9 and caspase-3. PEITC was also combined with the HO-1 inhibitor zinc protoporphyrin IX and the inducer hemin to assess whether HO-1 determines cell survival and ROS generation. The results of the present study suggest that PEITC may be a potential anti-tumor compound for CML therapy, and that HO-1 has a critical function in PEITC-induced apoptosis and ROS generation.

ROS accumulation by PEITC selectively kills ovarian cancer cells via UPR-mediated apoptosis

“…The apoptotic cell death in these cell lines was reversed by the ROS scavenger, NAC. A number of studies are consistent with our results, ROS mediated cell death in many types of cancer cells ( 37 , 45 , 46 ).…”

Proapoptotic effects of heme oxygenase-1 inhibitor on Kasumi-1 cells via the ATF4/CHOP/Ire-1α pathway

“…The regulation of HO-1 is under the control of signaling components (Shirley and Micheau, 2010;Rushworth et al, 2011) and many transcription factors, including nuclear factor-(erythroid-derived 2)-like 2-related factor 2, activating transcription factor 4 (ATF4), and activator protein-1 (He et al, 2001;Yu et al, 2014). Additionally, its expression is closely related to the endoplasmic reticulum apoptotic pathway mediated by caspases and the CCAAT-enhancer-binding protein homologous protein (CHOP) pathway (Wang et al, 2014b).…”

Phenethyl isothiocyanate suppresses cervical carcinoma metastasis potential and its molecular mechanism

“…Previous studies have also demonstrated that isothiocyanates exhibit antitumor activity, inhibiting growth and metastasis in various human cancer cell models. Other studies have revealed that phenethyl isothiocyanate (PEITC) suppresses the growth of cancer cells in vitro and in vivo (6). Several cellular responses to this potential chemopreventative agent have been previously described, including apoptosis mediated by c-Jun amino terminal kinase and extracellular signal-regulated kinase (7,8).…”