Acanthoic acid induces cell apoptosis through activation of the p38 MAPK pathway in HL-60 human promyelocytic leukaemia

• Published in: Food chemistry Vol. 135; no. 3; pp. 2112 - 2117
• Main Authors: Kim, Kil-Nam, Ham, Young Min, Moon, Ji-Young, Kim, Min-Jin, Jung, Yong-Hwan, Jeon, You-Jin, Lee, Nam Ho, Kang, Nalae, Yang, Hye-Mi, Kim, Daekyung, Hyun, Chang-Gu
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01.12.2012; Elsevier
• Subjects: Acanthoic acid (ACAN); Acanthopanax koreanum; acids; Apoptosis; Apoptosis - drug effects; Biological and medical sciences; caspase-3; cell proliferation; Cell Survival - drug effects; Diterpenes - pharmacology; Eleutherococcus; Eleutherococcus - chemistry; Food industries; Fundamental and applied biological sciences. Psychology; HL-60 Cells; Humans; leukemia; Leukemia, Promyelocytic, Acute - drug therapy; Leukemia, Promyelocytic, Acute - enzymology; Leukemia, Promyelocytic, Acute - metabolism; MAP Kinase Signaling System - drug effects; mechanism of action; mitogen-activated protein kinase; Mitogen-activated protein kinase (MAPK); p38 Mitogen-Activated Protein Kinases - metabolism; phosphorylation; Plant Extracts - pharmacology; viability; PBS; DMSO; JNK; Mitogen-activated protein kinase (MAPK); Acanthoic acid (ACAN); MAPK; MTT; Acanthopanax koreanum; ACAN; PI; HL-60 cells; ERK; Apoptosis; Human; Enzyme; Transferases; Non-specific serine/threonine protein kinase; Activation
• ISSN: 0308-8146; 1873-7072
• DOI: 10.1016/j.foodchem.2012.05.067

► We examined the molecular mechanisms involved in acanthoic acid-induced apoptosis in HL-60 cells. ► Acanthoic acid (ACAN) induced apoptosis in HL-60 cells via activation of caspase-3 and inhibition of Bcl-xL. ► A specific p38 MAPK inhibitor (SB203580) significantly blocks ACAN-induced apoptosis and cell viability. ► Thus, the activation of p38 MAPK may play an important role in ACAN-induced apoptosis. The present study was designed to evaluate the molecular mechanisms of the action of acanthoic acid (ACAN) from Acanthopanax koreanum (Araliaceae) against HL-60 human promyelocytic leukaemia cells. ACAN reduced the proliferation of HL-60 cells in a dose- and time-dependent manner accompanied by the induction of apoptosis. Possible mechanisms of ACAN-induced apoptosis were also examined. The results showed that ACAN-induced the phosphorylation of members of the mitogen-activated protein kinase (MAPK) family, c-Jun N-terminal kinase (JNK), p38 MAPK (p38), and extracellular signal-regulated kinase (ERK). A specific p38 MAPK inhibitor (SB203580) significantly blocked ACAN-induced apoptosis and cell viability, whereas an ERK inhibitor (PD98059) and JNK inhibitor (SP600125) had no effect. Moreover, ACAN induced the cleavage of caspase-3 and poly-ADP-ribose polymerase (PARP), and decreased the level of Bcl-xL, but these effects were inhibited by SB203580 pre-treatment. These results strongly suggest that ACAN may have cancer chemopreventive and therapeutic potential, due to its ability to activate the p38 MAPK-mediated signalling pathways.