Costunolide induces differentiation of human leukemia HL-60 cells

Abstract

Costunolide has been reported to be a cytotoxic and chemopreventive agent. This work investigated the mechanism of the antiproliferative effect of costunolide and determined that it induced differentiation of the human leukemia cell line HL-60. Costunolide exhibited a potent antiproliferative activity against HL-60 cells. It was also found to be a potent inducer of differentiation in human leukemia derived HL-60 cells through the examination of differentiation markers, as assessed by the reduction of nitroblue-tetrazolium, the increase in esterase activities and phagocytic activity, morphology change and the expression of CD14 and CD66b surface antigens. These results, accompanied by a decline in the expression of c-myc protein, suggest that costunolide induces differentiation of human leukemia cells to granulocytes and monocytes/macrophages lineage.

Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C NMR spectral data and biological properties

“…Costunolide markedly increased the degree of HL-60 leukemia cell differentiation when simultaneously combined with 5 nM 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3). The results indicate that PKC, PI3-K, ERK and NF-jB may be involved in 1,25-(OH)2D3-mediated cell differentiation enhanced by costunolide (Choi et al, 2002b;Kim et al, 2002).…”

Costunolide: A novel anti-cancer sesquiterpene lactone

“…It also reported that, costunolide is involved to inhibit the expression of inducible nitric oxide synthase (De Marino et al, 2005;Fukuda et al, 2001;Matsuda et al, 2000;Park et al, 1996) and the DNA-binding activity of NF-κB (Castro et al, 2000;Koo et al, 2001;Stefani et al, 2006) and has potential as natural herbicide (Macias et al, 1999). Furthermore, costunolide potentiated 1,25-(OH)2D3-induced differentiation in HL-60 promyelocytic leukemia cells (Choi et al, 2002b;Kim et al, 2008;Kim et al, 2002), via the interference with NF-κB activation. Further studies demonstrate that costunolide has antitumor potential by inhibiting proliferation, inducing apoptosis and reducing invasion and metastasis of a wide variety of tumor cells, including breast cancer cells (Bocca et al, 2004;Choi et al, 2005;Choi et al, 2011), hepatocellular carcinoma cells (Chen et al, 1995;Liu et al, 2011a;Sun et al, 2003), prostate cancer cells (Hsu et al, 2011), leukemia cells (Choi et al, 2002a;Choi and Lee, 2009;Choi et al, 2002b;Hibasami et al, 2003;Kanno et al, 2008;Kim et al, 2008;Kim et al, 2002;Kim et al, 2011b;Komiya et al, 2004;Lee et al, 2001;Song et al, 2001;Srivastava et al, 2006), gastric cancer cells (Ko et al, 2005;Rasul et al, 2011), colon cancer cells (Kawamori et al, 1995;Mori et al, 1994), melanoma cells (Chen et al, 2007;…”

“…Furthermore, costunolide potentiated 1,25-(OH)2D3-induced differentiation in HL-60 promyelocytic leukemia cells (Choi et al, 2002b;Kim et al, 2008;Kim et al, 2002), via the interference with NF-κB activation. Further studies demonstrate that costunolide has antitumor potential by inhibiting proliferation, inducing apoptosis and reducing invasion and metastasis of a wide variety of tumor cells, including breast cancer cells (Bocca et al, 2004;Choi et al, 2005;Choi et al, 2011), hepatocellular carcinoma cells (Chen et al, 1995;Liu et al, 2011a;Sun et al, 2003), prostate cancer cells (Hsu et al, 2011), leukemia cells (Choi et al, 2002a;Choi and Lee, 2009;Choi et al, 2002b;Hibasami et al, 2003;Kanno et al, 2008;Kim et al, 2008;Kim et al, 2002;Kim et al, 2011b;Komiya et al, 2004;Lee et al, 2001;Song et al, 2001;Srivastava et al, 2006), gastric cancer cells (Ko et al, 2005;Rasul et al, 2011), colon cancer cells (Kawamori et al, 1995;Mori et al, 1994), melanoma cells (Chen et al, 2007;Park et al, 2001b), cervical cancer cells (Sun et al, 2003), KB and P388 tumor cell (Mondranondra et al, 1990), and platinum-resistant human ovarian cancer cells . It was also reported that costunolide inhibited angiogenic response by blocking the angiogenic factor signaling pathway (Jeong et al, 2002) and microtubule-interactting activity of costunolide (Bocca et al, 2004).…”

Metabolic transformation of breast cancer in a MCF-7 xenograft mouse model and inhibitory effect of volatile oil from Saussurea lappa Decne treatment

“…The anticancer activity in vitro and the pharmacological mechanism of Cos have been reported in many papers (Bocca et al 2004;Choi et al 2002;Jeong et al 2002).…”