Roles of anti- and pro-oxidant potential of cinnamic acid and phenylpropanoid derivatives in modulating growth of cultured cells

Abstract

Cinnamic acid (CiA) and phenylpropanoid derivatives are widely distributed in plant foods. In this study, anti- and pro-oxidant properties of the derivatives and their roles in modulating cell growth were investigated. Ferulic acid, sinapinic acid, caffeic acid (CaA), and 3,4-dihydroxyhydrocinnamic acid (DHC) showed strong radical scavenging activities. They, except DHC, also performed considerable inhibitory effects on lipid peroxidation and reduced levels of intracellular reactive oxygen species (ROS). CaA and DHC, however, produced substantial amount of H₂O₂ with oxidative degradation in culture conditions. CaA and DHC (> 400 μM) showed potent cytotoxic effects which were abolished by superoxide dismutase/catalase; they significantly enhanced cell growth ROS-dependently at low levels (~ 100 μM). CiA derivatives without bearing hydroxyl group did not show any appreciable antioxidant activities. The results indicate that CiA derivatives with ortho-dihydroxyl group had strong anti- and pro-oxidant properties, which also play an important role in modulating cell growth.

Supplementary information: The online version contains supplementary material available at 10.1007/s10068-022-01042-x.

Keywords: Antioxidant; Cell growth; Cinnamic acid derivative; Phenylpropanoid; Prooxidant; Reactive oxygen species.

Fig. 1

Structures of CiA and phenylpropanoid derivatives used in this study

Fig. 2

Effects of CiA and phenylpropanoid derivatives on intracellular ROS level. HCT 116 cells were treated with each compound for 90 min (A) or were incubated with each derivative first, and treatment was replaced with H₂O₂ (500 μM) for 30 min (B). Intracellular ROS levels were observed by measuring fluorescence from added DCFH-DA (20 μM) with excitation at 485 nm and an emission at 535 nm. Each value represents the mean ± SD (n = 8). *,** significantly different from the corresponding control according to Student’s t-test (*p < 0.05; **, ##p < 0.01)

Fig. 3

H₂O₂ generation, formation of oxidative products from phenylpropanoid derivatives, and their cytotoxic properties. H₂O₂ levels (μM) from FeA, SiA, CaA, and DHC (each 400 μM) were detected at indicated time points (A). Formation of their oxidative products was also monitored at 405 nm (B). Cytotoxic effect of each compound on HCT 116 cells were also evaluated using the MTT assay (C). Each value represents the mean ± SD (n = 4 in A and B, n = 8–24 in C). Different letters indicate a significant difference (p < 0.05) based on one-way ANOVA and the Tukey’s HSD test (in A and B). *,** significantly different from its corresponding control according to Student’s t-test (*p < 0.05; **p < 0.01 in c)

Fig. 4

Modulatory effects on cell death and growth of phenylpropanoid derivatives by SOD/catalase, EDTA and their oxidation status. HCT 116 cells were incubated with FeA, SiA, CaA, and DHC (400 and 800 μM) in the presence or absence of SOD (15 unit/mL)/catalase (30 units/mL) (A) or of 1 mM EDTA (B) for 24 h. Each value represents the mean ± S.D. (n = 8). Cell growth modulation of CaA and DHC (C) up to 200 μM and their oxidation products (pre-incubation at 37 °C for 24 h) (D) in the absence or presence of SOD/catalase was also analyzed. Each value represents the mean ± S.D. (n = 8). *,**Significantly different from its corresponding control according to Student’s t-test (*p < 0.05; **p < 0.01)