Curcumin differentially affects cell cycle and cell death in acute and chronic myeloid leukemia cells

Abstract

Curcumin is a phytochemical with potent anti-neoplastic properties. The antitumoral effects of curcumin in cells derived from chronic or acute myeloid leukemia have been already described. However, a comparative study of the cytostatic and cytotoxic effects of curcumin on chronic and acute myeloid leukemia cells has not yet been performed. In the present study, the cellular effects of curcumin on cell lines derived from chronic or acute myeloid leukemia were examined. Dose and time-response assays were performed with curcumin on HL-60 and K562 cells. Cell viability was evaluated with trypan blue exclusion test and cell death by flow cytometry using a fluorescent molecular probe. A cell cycle profile was analyzed, and protein markers of cell cycle progression and cell death were investigated. In the present study, the K562 cells showed a higher sensitivity to the cytostatic and cytotoxic effects of curcumin compared with HL-60. In addition, curcumin induced G1 phase arrest in HL-60 cells and G2/M phase arrest in K562 cells. Furthermore, curcumin-related cell death in HL-60 was associated with the processed forms of caspases-9 and -3 proteins, whereas in K562 cells, both the processed and the unprocessed forms were present. Accordingly, activity of these caspases was significantly higher in HL-60 cells compared with that in K562. In conclusion, curcumin elicits different cellular mechanisms in chronic or acute myeloid leukemia cells and the powerful antitumoral effect was more potent in K562 compared with HL-60 cells.

Synergistic Cytotoxicity of Methyl 4-Hydroxycinnamate and Carnosic Acid to Acute Myeloid Leukemia Cells via Calcium-Dependent Apoptosis Induction

“…Various natural and synthetic phenolic compounds have been shown to possess anti-leukemic potential in preclinical models (De Martino et al, 2011), curcumin (CUR) being one of the most studied polyphenols (Kelkel et al, 2010). However, the majority of in vitro studies employed high supraphysiological concentrations of CUR (Lin et al, 2008; Zhang et al, 2017; Martínez-Castillo et al, 2018) which induced generalized cellular stress events leading to cell death, such as oxidative stress (Lin et al, 2008; Yoon et al, 2012), ER stress (Lin et al, 2008; Cao et al, 2013), or mitochondrial damage (Yoon et al, 2012; Cao et al, 2013; Xu et al, 2015). We have previously shown that CUR combined with another polyphenol, carnosic acid (CA), at noncytotoxic concentrations of each agent synergistically and selectively killed AML cells by inducing massive apoptosis both in vitro and in vivo (Pesakhov et al, 2010, 2016).…”

The Anti-Leukemic Activity of Natural Compounds

“…Curcumin induced apoptosis in cell lines derived from chronic and acute myeloid leukemia by distinct cellular mechanisms. Thus, curcumin-induced apoptosis in HL-60 cells was caspase-dependent, whereas in K562 cells, they underwent apoptosis in a caspase-independent manner [ 60 ].…”

Self-assembled fluorescent hybrid nanoparticles-mediated collaborative lncRNA CCAT1 silencing and curcumin delivery for synchronous colorectal cancer theranostics

“…Curcumin (Cur), is a natural extraction of turmeric, which has been confirmed to have the anti-tumor capacity, including the resistance of development, metastasis, and progression in multiple cancer types, such as CRC, pancreatic cancer, myeloid leukemia, and breast cancer [ 24 – 27 ]. Cur brings its anti-cancer effects into play by targeting multiple intracellular signaling pathways.…”