Browse > Article
http://dx.doi.org/10.7314/APJCP.2014.15.22.9915

Inhibition Effects of Lamellarin D on Human Leukemia K562 Cell Proliferation and Underlying Mechanisms  

Zhang, Nan (Department of Pharmacology, Tianjin Children's Hospital)
Wang, Dong (Tianjin Key Laboratory of Tumor Prevention and Therapeutics, Department of Pharmacy of Tianjin Medical University Cancer Institute and Hospital)
Zhu, Yu (Department of Clinical Laboratory, Tianjin Huanhu Hospital, Tianjin Key Laboratory of Cerebral Vessels and Neural Degeneration)
Wang, Jian (Department of Pharmacology, Tianjin Children's Hospital)
Lin, Hong (Department of Pharmacology, Tianjin Children's Hospital)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.15, no.22, 2014 , pp. 9915-9919 More about this Journal
Abstract
Lamellarin D (LamD) is a marine alkaloid with a pronounced cytotoxicity against a large panel of cancer cells, affecting cell growth and inducing apoptosis. However, the molecular mechanisms of action of this compound are poorly understood. In this study, the anticancer efficacy of LamD was investigated in human leukemia K562 cells. The results showed suppressed cell proliferation and induction of G0/G1-phase arrest,while expression of CDK1, and activity of smad3 and smad5 were reduced, but that of p27, p53 and STGC3 was increased. LamD induced cell apoptosis through activation of caspases-8/-3, inhibition of survivin and Bcl-2, suggesting that this compound may also act through a caspase-independent pathway. Moreover, LamD inhibited the secretion of TGF-${\beta}$, IL-$1{\beta}$, IL-6, IL-8 and other inflammatory cytokines and the transcriptional activity of transcription factor NF-${\kappa}B$ in human leukemia K562 cells.Taken together, our results suggest that LamD-mediated inhibition of leukemia cell proliferation may be related to the induction of apoptosis and the regulation of cell cycle, tumor-related gene expression and cytokine expression, which may provide a new way of thinking for the treatment leukemia.
Keywords
Lamellarin D; proliferation; apoptosis; K562 cells; leukemia;
Citations & Related Records
Times Cited By KSCI : 3  (Citation Analysis)
연도 인용수 순위
1 Banerjee P, Basu A, Wegiel B, et al (2012).Heme oxygenase-1 promotes survival of renal cancer cells through modulation of apoptosis- and autophagy-regulating molecules. J Biol Chem, 38, 32113-23.
2 Chanmee T, Ontong P, Konno K,et al (2014).Tumor-associated macrophages as major players in the tumor microenvironment. Cancers (Basel), 6, 1670-90.   DOI
3 Chittchang M, Batsomboon P, Ruchirawat S, et al (2009). Cytotoxicities and structure-activity relationships of natural and unnatural lamellarins toward cancer cell lines. ChemMedChem, 4, 457-65.   DOI
4 Davis AS, Viera AJ, Mead MD (2014). Leukemia: an overview for primary care. Am Fam Physician, 89,731-8.
5 Deng S, Hu B, Shen KP, et al (2012).Inflammation, macrophage in cancer progression and chinese herbal treatment. J Basic Clin Pharm, 3, 269-72.   DOI
6 El-Kadre LJ, Tinoco AC (2013). Interleukin-6 and obesity: the crosstalk between intestine, pancreas and liver. Curr Opin Clin Nutr Metab Care, 16, 564-8.
7 Gallego MA, Ballot C, Kluza J, et al (2008). Overcoming chemoresistance of non-small cell lung carcinoma through restoration of an AIF-dependent apoptotic pathway. Oncogene, 27, 1981-92.   DOI   ScienceOn
8 Itzykson R, Solary E (2013). An evolutionary perspective on chronic myelomonocytic leukemia. Leukemia, 27, 1441-50.   DOI
9 Kojima H, Inoue T, Kunimoto H, et al (2013). IL-6-STAT3 signaling and premature senescence. JAKSTAT, 2, 25763.
10 Lai CS, Li S, Miyauchi Y, et al (2013). Potent anti-cancer effects of citrus peel flavonoids in human prostate xenograft tumors. Food Funct, 4, 944-9.   DOI
11 Landskron G, De la Fuente M, Thuwajit P, et al (2014). Chronic inflammation and cytokines in the tumor microenvironment. J Immunol Res, 2014, 149185.
12 Leibovich-Rivkin T, Liubomirski Y, Bernstein B, et al (2013). Inflammatory factors of the tumor microenvironment induce plasticity in nontransformed breast epithelial cells: EMT, invasion, and collapse of normally organized breast textures. Neoplasia, 15,1330-46.   DOI
13 Li Y, Wang L, Pappan L,et al (2012). IL-$1{\beta}$ promotes stemness and invasiveness of colon cancer cells through Zeb1 activation. Mol Cancer, 11, 87.
14 Li Z, Zhang LJ, Zhang HR, et al (2014). Tumor-derived transforming growth factor-$\beta$ is critical for tumor progression and evasion from immune surveillance. Asian Pac J Cancer Prev, 15, 5181-6.   과학기술학회마을   DOI
15 Prabhu VV, Guruvayoorappan C (2012). Anti-inflammatory and anti-tumor activity of the marine mangrove Rhizophora apiculata. J Immunotoxicol, 9, 341-52.   DOI   ScienceOn
16 Manola KN (2013). Cytogenetic abnormalities in acute leukaemia of ambiguous lineage: an overview. Br J Haematol, 163, 24-39.   DOI
17 Peppicelli S, Bianchini F, Calorini L (2014). Inflammatory cytokines induce vascular endothelial growth factor-C expression in melanoma-associated macrophages and stimulate melanoma lymph node metastasis. Oncol Lett, 8, 1133-8.
18 Plisson F, Huang XC, Zhang H,et al (2012). Lamellarins as inhibitors of P-glycoprotein -mediated multidrug resistance in a human colon cancer cell line. Chem Asian J, 7, 1616-23.   DOI
19 Sakthivel KM, Guruvayoorappan C (2013). Acacia ferruginea inhibits tumor progression by regulating inflammatory mediators-(TNF-a, iNOS, COX-2, IL-$1{\beta}$, IL-6, IFN-$\gamma$, IL-2, GM-CSF) and pro-angiogenic growth factor- VEGF. Asian Pac J Cancer Prev, 14, 3909-19.   과학기술학회마을   DOI   ScienceOn
20 Taylor MA, Lee YH, Schiemann WP (2013). Role of TGF-$\beta$ and the tumor microenvironment during mammary tumorigenesis. Gene Expr, 15, 117-32.
21 Tohme R, Darwiche N, Gali-Muhtasib H (2011). A journey under the sea: the quest for marine anti-cancer alkaloids. Molecules, 16, 9665-96.   DOI
22 Vilela FM, Syed DN, Chamcheu JC, et al (2014). Biotransformed soybean extract (BSE) inhibits melanoma cell growth and viability in vitro: involvement of nuclear factor-kappa B signaling. PLoS One, 9, 103248.   DOI
23 Zhu Y, Zhang L, Zhang GD, et al (2014). Potential mechanisms of benzyl isothiocyanate suppression of invasion and angiogenesis by the U87MG human glioma cell line. Asian Pac J Cancer Prev, 15, 8225-8.   과학기술학회마을   DOI
24 Vinken M, Landesmann B, Goumenou M, et al (2013). Development of an adverse outcome pathway from drugmediated bile salt export pump inhibition to cholestatic liver injury. Toxicol Sci, 136, 97-106.   DOI
25 Voronov E, Carmi Y, Apte RN (2014). The role IL-1 in tumormediated angiogenesis. Front Physiol, 5, 114.
26 Wang JH, Chen WL, Li JM, et al (2013). Prognostic significance of 2-hydroxyglutarate levels in acute myeloid leukemia in China. Proc Natl Acad Sci U S A, 110, 17017-22.   DOI