Ascorbic acid inhibits TPA-induced HL-60 cell differentiation by decreasing cellular H2O2 and ERK phosphorylation

Abstract

Retinoic acid (RA), vitamin D and 12-O‑tetradecanoyl phorbol-13-acetate (TPA) can induce HL-60 cells to differentiate into granulocytes, monocytes and macrophages, respectively. Similar to RA and vitamin D, ascorbic acid also belongs to the vitamin family. High‑dose ascorbic acid (>100 µM) induces HL‑60 cell apoptosis and induces a small fraction of HL‑60 cells to express the granulocyte marker, CD66b. In addition, ascorbic acid exerts an anti‑oxidative stress function. Oxidative stress is required for HL‑60 cell differentiation following treatment with TPA, however, the effect of ascorbic acid on HL‑60 cell differentiation in combination with TPA treatment remains to be fully elucidated. The aim of the present study was to investigate the cellular effects of ascorbic acid treatment on TPA-differentiated HL-60 cells. TPA-differentiated HL-60 cells were used for this investigation, this study and the levels of cellular hydrogen peroxide (H2O2), caspase activity and ERK phosphorylation were determined following combined treatment with TPA and ascorbic acid. The results demonstrated that low‑dose ascorbic acid (5 µM) reduced the cellular levels of H2O2 and inhibited the differentiation of HL‑60 cells into macrophages following treatment with TPA. In addition, the results of the present study further demonstrated that low‑dose ascorbic acid inactivates the ERK phosphorylation pathway, which inhibited HL‑60 cell differentiation following treatment with TPA.

KSHV reduces autophagy in THP-1 cells and in differentiating monocytes by decreasing CAST/calpastatin and ATG5 expression

“…63 TPA also stimulates in vitro differentiation of monocytoid cells [64][65][66] although the possible underlying mechanisms have not been explored. Thus, we investigated whether TPA could activate autophagy in THP-1 cells during their in vitro differentiation and found that it induced autophagy in these cells, as LC3-II increased and SQSTM1 decreased after 48 h of treatment (Fig.…”

Empowering γδ T‐cell functionality with vitamin C

“…In cytokine‐activated endothelial cells, VitC inhibited NF‐κB activation which was mediated through inhibition of IκBα kinase by DHA [28]. Low‐dose VitC was reported to inhibit the phorbolester‐driven differentiation of myeloid HL‐60 cells, associated with the inhibition of ERK phosphorylation [29]. On the other hand, VitC activates the JAK2/STAT2 pathway when VitC is taken up via the SVCT2 transporter [30].…”

Ubiquitin-specific peptidase 3 induces TPA-mediated leukemia cell differentiation via regulating H2AK119ub

“…HL-60 cells, which are human AML cells, have been used as an excellent model for HL-60 cell differentiation by chemotherapeutic agents. HL-60 cells can be induced to differentiate into granulocytes, monocytes, and macrophages by several agents, such as retinoic acid (RA), ascorbic acid (vitamin C), vitamin D, and 12-O-tetradecanoyl phorbol-13-acetate (TPA), respectively (Zylber-Katz and Glazer 1985; Trayner et al 1998; Yiang et al 2015). TPA decreased the number of myeloblasts and relieved remissions in some of the patients (Han et al 1998).…”