Potential Anti-Cancer Activities and Mechanisms of Costunolide and Dehydrocostuslactone

International Journal of Molecular Sciences - Tập 16 Số 5 - Trang 10888-10906
Xuejing Lin1, Zhangxiao Peng2, Changqing Su3
1Department of Molecular Oncology, Eastern Hepatobiliary Surgical Hospital & National Center of Liver Cancer, Second Military Medical University, Shanghai, 200438, China
2Department of Molecular Oncology, Eastern Hepatobiliary Surgical Hospital & National Center of Liver Cancer, Second Military Medical University, Shanghai 200438, China. [email protected].
3Department of Molecular Oncology, Eastern Hepatobiliary Surgical Hospital & National Center of Liver Cancer, Second Military Medical University, Shanghai 200438, China. [email protected].

Tóm tắt

Costunolide (CE) and dehydrocostuslactone (DE) are derived from many species of medicinal plants, such as Saussurea lappa Decne and Laurus nobilis L. They have been reported for their wide spectrum of biological effects, including anti-inflammatory, anticancer, antiviral, antimicrobial, antifungal, antioxidant, antidiabetic, antiulcer, and anthelmintic activities. In recent years, they have caused extensive interest in researchers due to their potential anti-cancer activities for various types of cancer, and their anti-cancer mechanisms, including causing cell cycle arrest, inducing apoptosis and differentiation, promoting the aggregation of microtubule protein, inhibiting the activity of telomerase, inhibiting metastasis and invasion, reversing multidrug resistance, restraining angiogenesis has been studied. This review will summarize anti-cancer activities and associated molecular mechanisms of these two compounds for the purpose of promoting their research and application.

Từ khóa


Tài liệu tham khảo

Koehn, 2005, The evolving role of natural products in drug discovery, Nat. Rev. Drug Discov., 4, 206, 10.1038/nrd1657

Pan, 2010, The continuing search for antitumor agents from higher plants, Phytochem. Lett., 3, 1, 10.1016/j.phytol.2009.11.005

DeVita, V.T., Hellman, S., and Rosenberg, S.A. (2008). Cancer: Principles and Practice of Oncology, Lippincott-Williams & Wilkins. [8th ed.].

Butturini, 2011, Two naturally occurring terpenes, dehydrocostuslactone and costunolide, decrease intracellular GSH content and inhibit STAT3 activation, PLoS ONE, 6, e20174, 10.1371/journal.pone.0020174

Liu, 2011, Costunolide causes mitotic arrest and enhances radiosensitivity in human hepatocellular carcinoma cells, Radiat. Oncol., 6, 56, 10.1186/1748-717X-6-56

Hsu, 2009, Dehydrocostuslactone, a medicinal plant-derived sesquiterpene lactone, induces apoptosis coupled to endoplasmic reticulum stress in liver cancer cells, J. Pharmacol. Exp. Ther., 329, 808, 10.1124/jpet.108.148395

Choi, 2010, Evaluation of anticancer activity of dehydrocostuslactone in vitro, Mol. Med. Rep., 3, 185

Pitchai, 2014, In vitro and in silico evaluation of NF-κB targeted costunolide action on estrogen receptor-negative breast cancer cells-a comparison with normal breast cells, Phytother. Res., 28, 1499, 10.1002/ptr.5155

Choi, 2009, Antiproliferative effects of dehydrocostuslactone through cell cycle arrest and apoptosis in human ovarian cancer SK-OV-3 cells, Int. J. Mol. Med., 23, 211

Sun, 2003, Cytotoxic sesquiterpene lactones from the root of Saussurea lappa, J. Nat. Prod., 66, 1175, 10.1021/np030147e

Kim, 2008, Apoptosis of DU145 human prostate cancer cells induced by dehydrocostus lactone isolated from the root of Saussurea lappa, Food Chem. Toxicol., 46, 3651, 10.1016/j.fct.2008.08.038

Kim, 2012, The hexane extract of Saussurea lappa and its active principle, dehydrocostus lactone, inhibit prostate cancer cell migration, J. Med. Food, 15, 24, 10.1089/jmf.2011.1735

Rasul, 2013, Induction of apoptosis by costunolide in bladder cancer cells is mediated through ROS generation and mitochondrial dysfunction, Molecules, 18, 1418, 10.3390/molecules18021418

Robinson, 2008, A new sesquiterpene lactone from the roots of Saussurea lappa: Structure–anticancer activity study, Bioorg. Med. Chem. Lett., 18, 4015, 10.1016/j.bmcl.2008.06.008

Peng, 2013, A platform for fast screening potential anti-breast cancer compounds in traditional Chinese medicines, Biomed. Chromatogr., 27, 1759, 10.1002/bmc.2990

Cateni, 2006, Synthesis and biological properties of new α-methylene-γ-butyrolactones and α, β-unsaturated δ-lactones, Eur. J. Med. Chem., 41, 192, 10.1016/j.ejmech.2005.10.009

Romagnoli, 2005, Design, synthesis, and biological evaluation of hybrid molecules containing α-methylene-γ-butyrolactones and α-bromoacryloyl moieties, J. Med. Chem., 48, 7906, 10.1021/jm058012o

Wang, 2008, Effects of eighteen sesquiterpenes from Saussurea lappa on the proliferation of six human cancer cell lines, Nat. Prod. Res. Dev., 20, 808

Cho, 1998, Inhibitory effect of sesquiterpene lactones from Saussurea lappa on tumor necrosis factor-α production in murine macrophage like cells, Planta Med., 64, 594, 10.1055/s-2006-957528

Jeong, 2007, The α-methylene-γ-butyrolactone moiety in dehydrocostus lactone is responsible for cytoprotective heme oxygenase-1 expression through activation of the nuclear factor E2-related factor 2 in HepG2 cells, Eur. J. Pharmacol., 565, 37, 10.1016/j.ejphar.2007.02.053

Butturini, 2014, Costunolide and dehydrocostuslactone, two natural sesquiterpene lactones, ameliorate the inflammatory process associated to experimental pleurisyinmice, Eur. J. Pharmacol., 730, 107, 10.1016/j.ejphar.2014.02.031

Kassuya, 2009, Antipyretic and anti-inflammatory properties of the ethanolic extract, dichloromethane fraction and costunolide from Magnolia ovata (Magnoliaceae), J. Ethnopharmacol., 124, 369, 10.1016/j.jep.2009.06.003

Kuo, 2009, Dehydrocostuslactone disrupts signal transducers and activators of transcription 3 through up-regulation of suppressor of cytokine signaling in breast cancer cells, Mol. Cancer Ther., 8, 1328, 10.1158/1535-7163.MCT-08-0914

Park, 2001, Costunolide, a sesquiterpene from the stem bark of Magnolia sieboldii, inhibits the RAS-farnesyl-proteintransferase, Planta Med., 67, 358, 10.1055/s-2001-14315

Chen, 1995, Active compounds from Saussurea lappa Clarks that suppress hepatitis B virus surface antigen gene expression in human hepatoma cells, Antivir. Res., 27, 99, 10.1016/0166-3542(94)00083-K

Lee, 2014, Growth inhibitory, bactericidal, and morphostructural effects of dehydrocostus lactone from Magnolia sieboldii Leaves on antibiotic-susceptible and -resistant strains of Helicobacter pylori, PLoS ONE, 9, e95530, 10.1371/journal.pone.0095530

Duraipandiyan, 2012, Antimicrobial activity of sesquiterpene lactones isolated from traditional medicinal plant, Costus speciosus (Koen ex.Retz.) Sm, BMC Complement. Altern. Med., 12, 13, 10.1186/1472-6882-12-13

Barrero, 2000, New sources and antifungal activity of sesquiterpene lactones, Fitoterapia, 71, 60, 10.1016/S0367-326X(99)00122-7

Eliza, 2010, Antioxidant activity of costunolide and eremanthin isolated from Costus speciosus (Koen ex.Retz) Sm, Chem. Biol. Interact., 188, 467, 10.1016/j.cbi.2010.08.002

Seo, 2012, The effects of dehydrocostus lactone on osteoblastic MC3T3-E1 cells in redox changes and PI3K/Akt/CREB, Immunopharmacol. Immunotoxicol., 34, 810, 10.3109/08923973.2012.657799

Upadhyay, 1996, Studies on antidiabetic medicinal plants used in Indian folklore, Aryavaidyan, 9, 159

Sutar, 2011, Antiulcerogenic activity of Saussurea lappa root, Int. J. Pharm. Life Sci., 2, 516

Seki, 1991, Motility inhibitory effect on Anchusan and Jintan and its active components in Anisakis type larvae, Yakuri Chiryo, 19, 265

Triana, 2003, Sesquiterpenoid derivatives from Gonospermum elegans and their cytotoxic activity for HL-60 human promyelocytic cells, J. Nat. Prod., 66, 943, 10.1021/np020390y

Triana, 2008, Sesquiterpene lactones from Gonospermum gomerae and G. fruticosum and their cytotoxic activities, J. Nat. Prod., 71, 2015, 10.1021/np800474v

Ramasamy, 2008, Multitargeted therapy of cancer by silymarin, Cancer Lett., 269, 352, 10.1016/j.canlet.2008.03.053

Liu, 2014, Anti-tumor activities of matrine and oxymatrine: Literature review, Tumour Biol., 35, 5111, 10.1007/s13277-014-1680-z

Kim, 2002, Potentiation of 1,25-dihydroxyvitamin D3-induced differentiation of human promyelocytic leukemia cells into monocytes by costunolide, a germacranolide sesquiterpene lactone, Biochem. Pharmacol., 64, 1233, 10.1016/S0006-2952(02)01292-3

Yang, 2011, Costunolide induces apoptosis in platinum-resistant human ovarian cancer cells by generating reactive oxygen species, Gynecol. Oncol., 123, 588, 10.1016/j.ygyno.2011.08.031

Hao, 2010, Inhibitory efects of sesquiterpenes from Saussurealappa on the vascular endothelial growth factor, Nat. Prod. Res. Dev., 22, 687

Obaya, 2002, Regulation of cyclin-Cdk activity in mammalian cells, Cell. Mol. Life Sci., 59, 126, 10.1007/s00018-002-8410-1

Choi, 2012, Induction of Fas-mediated extrinsic apoptosis, p21WAF1-related G2/M cell cycle arrest and ROS generation by costunolide in estrogen receptor-negative breast cancer cells, MDA-MB-231, Mol. Cell. Biochem., 363, 119, 10.1007/s11010-011-1164-z

Rasul, 2012, Costunolide, a sesquiterpene lactone induces G2/M phase arrest and mitochondria-mediated apoptosis in human gastric adenocarcinoma SGC-7901 cells, J. Med. Plants Res., 6, 1191

Kretschmer, 2012, Effect of costunolide and dehydrocostus lactone on cell cycle, apoptosis, and ABC transporter expression in human soft tissue sarcoma, Planta Med., 78, 1749, 10.1055/s-0032-1315385

Lohberger, 2013, Sesquiterpene lactones downregulate G2/M cell cycle regulator proteins and affect the invasive potential of human soft tissue sarcoma cells, PLoS ONE, 8, e66300, 10.1371/journal.pone.0066300

Wang, 2012, Dehydrocostuslactone suppresses angiogenesis in vitro and in vivo through inhibition of Akt/GSK-3β and mTOR signaling pathways, PLoS ONE, 7, e31195, 10.1371/journal.pone.0031195

Hsu, 2011, Costunolide induces apoptosis through nuclear calcium2+ overload and DNA damage response in human prostate cancer, J. Urol., 185, 1967, 10.1016/j.juro.2010.12.091

Noh, 2014, p53 down-regulates SETDB1 gene expression during paclitaxel induced-cell death, Biochem. Biophys. Res. Commun., 28, 43, 10.1016/j.bbrc.2014.02.053

Gismondi, 2013, Antioxidant extracts of African medicinal plants induce cell cycle arrest and differentiation in B16F10 melanoma cells, Int. J. Oncol., 43, 956, 10.3892/ijo.2013.2001

Gismondi, 2014, Biochemical composition and antioxidant properties of Lavandula angustifolia Miller essential oil are shielded by propolis against UV radiations, Photochem. Photobiol., 90, 702, 10.1111/php.12339

Forni, 2014, Antineoplastic activity of strawberry (Fragaria × ananassa Duch.) crude extracts on B16-F10 melanoma cells, Mol. Biosyst., 10, 1255, 10.1039/C3MB70316A

Lee, 2001, Costunolide induces apoptosis by ROS-mediated mitochondrial permeability transition and cytochrome C release, Biol. Pharm. Bull., 24, 303, 10.1248/bpb.24.303

Coqueret, 2003, New roles for p21 and p27 cell-cycle inhibitors: A function for each cell compartment?, Trends Cell Biol., 13, 65, 10.1016/S0962-8924(02)00043-0

Bouissou, 2012, Interplay between microtubule dynamics and intracellular organization, Int. J. Biochem. Cell Biol., 44, 266, 10.1016/j.biocel.2011.11.009

Nogales, 2000, Structural insights into microtubule function, Annu. Rev. Biochem., 69, 277, 10.1146/annurev.biochem.69.1.277

Parker, 2014, Microtubules and their role in cellular stress in cancer, Front. Oncol., 4, 153, 10.3389/fonc.2014.00153

2014, Natural products as antimitotic agents, Curr. Top. Med. Chem., 14, 2274

Whipple, 2013, Parthenolide and costunolide reduce microtentacles and tumor cell attachment by selectively targeting detyrosinated tubulin independent from NF-κB inhibition, Breast Cancer Res., 15, R83, 10.1186/bcr3477

Bocca, 2004, A sesquiterpene lactone, costunolide, interacts with microtubule protein and inhibits the growth of MCF-7 cells, Chem. Biol. Interact., 147, 79, 10.1016/j.cbi.2003.10.008

Counter, 1992, Telomere shortening associated with chromosome instability is arrested in immortal cells which express telomerase activity, EMBO J., 11, 1921, 10.1002/j.1460-2075.1992.tb05245.x

Morin, 1989, The human telomere terminal transferase enzyme is a ribonucleoprotein that synthesizes TTAGGG repeats, Cell, 59, 521, 10.1016/0092-8674(89)90035-4

Kim, 1994, Specific association of human telomerase activity with immortal cells and cancer, Science, 266, 2011, 10.1126/science.7605428

Shay, 1996, Telomerase activity in human cancer, Curr. Opin. Oncol., 8, 66, 10.1097/00001622-199601000-00012

Choi, 2005, Inhibitory effects of costunolide on the telomerase activity in human breast carcinoma cells, Cancer Lett., 227, 153, 10.1016/j.canlet.2005.01.011

Kanno, 2008, Costunolide-induced apoptosis is caused by receptor-mediated pathway and inhibition of telomerase activity in NALM-6 cells, Biol. Pharm. Bull., 31, 1024, 10.1248/bpb.31.1024

Degterev, 2003, A decade of caspases, Oncogene, 22, 8543, 10.1038/sj.onc.1207107

Elmore, 2007, Apoptosis: A review of programmed cell death, Toxicol. Pathol., 35, 495, 10.1080/01926230701320337

Hengartner, 2000, The biochemistry of apoptosis, Nature, 407, 770, 10.1038/35037710

Spencer, 2011, Measuring and modeling apoptosis in single cells, Cell, 144, 926, 10.1016/j.cell.2011.03.002

Zhang, 2014, Oxymatrine induces mitochondria dependent apoptosis in human osteosarcoma MNNG/HOS cells through inhibition of PI3K/Akt pathway, Tumour Biol., 35, 1619, 10.1007/s13277-013-1223-z

Saelens, 2004, Toxic proteins released from mitochondria in cell death, Oncogene, 23, 2861, 10.1038/sj.onc.1207523

Garrido, 2006, Mechanisms of cytochrome c release from mitochondria, Cell Death Differ., 13, 1423, 10.1038/sj.cdd.4401950

Ekert, 2005, The mitochondrial death squad: Hardened killers or innocent bystanders?, Curr. Opin. Cell Biol., 17, 626, 10.1016/j.ceb.2005.09.001

Susin, 2000, Two distinct pathways leading to nuclear apoptosis, J. Exp. Med., 192, 571, 10.1084/jem.192.4.571

Cory, 2002, The Bcl2 family: Regulators of the cellular life-or-death switch, Nat. Rev. Cancer, 2, 647, 10.1038/nrc883

Kruyt, 2005, Cell death independent of caspases: A review, Clin. Cancer Res., 11, 3155, 10.1158/1078-0432.CCR-04-2223

Oh, 2004, Dehydrocostus lactone enhances tumor necrosis factor-α-induced apoptosis of human leukemia HL-60 cells, Immunopharmacol. Immunotoxicol., 26, 163, 10.1081/IPH-120037712

Yun, 2004, In vitro cytotoxicity of Mokko lactone in human leukemia HL-60 cells: Induction of apoptotic cell death by mitochondrial membrane potential collapse, Immunopharmacol. Immunotoxicol., 26, 343, 10.1081/IPH-200026863

Choi, 2009, Costunolide-induced apoptosis in human leukemia cells: Involvement of c-jun N-terminal kinase activation, Biol. Pharm. Bull., 32, 1803, 10.1248/bpb.32.1803

Kim, 2011, Costunolide induces apoptosis in human endometriotic cells through inhibition of the prosurvival Akt and nuclear factor κB signaling pathway, Biol. Pharm. Bull., 34, 580, 10.1248/bpb.34.580

Chicheportiche, 1997, TWEAK, a new secreted ligand in the tumor necrosis factor family that weakly induces apoptosis, J. Biol. Chem., 272, 32401, 10.1074/jbc.272.51.32401

Ashkenazi, 1998, Death receptors: Signaling and modulation, Science, 281, 1305, 10.1126/science.281.5381.1305

Blesa, 2005, Characterization of 8p21.3 chromosomal deletions in B-cell lymphoma: TRAIL-R1and TRAIL-R2 as candidate dosage-dependent tumor suppressor genes, Blood, 106, 3214, 10.1182/blood-2005-05-2013

Wajant, 2002, The Fas signaling pathway: More than a paradigm, Science, 296, 1635, 10.1126/science.1071553

Kischkel, 1995, Cytotoxicity-dependent APO-1 (Fas/CD95)-associated proteins form a death-inducing signaling complex (DISC) with the receptor, EMBO J., 14, 5579, 10.1002/j.1460-2075.1995.tb00245.x

Feldman, 2005, The unfolded protein response: A novel component of the hypoxic stress response in tumors, Mol. Cancer Res., 3, 597, 10.1158/1541-7786.MCR-05-0221

Moenner, 2007, Integrated endoplasmic reticulum stress responses in cancer, Cancer Res., 67, 10631, 10.1158/0008-5472.CAN-07-1705

Yung, 2007, Endoplasmic reticulum stress exacerbates ischemia-reperfusion-induced apoptosis through attenuation of Akt protein synthesis in human choriocarcinoma cells, FASEB J., 21, 872, 10.1096/fj.06-6054com

Hung, 2010, Oxidative and endoplasmic reticulum stress signaling are involved in dehydrocostuslactone-mediated apoptosis in human non-small cell lung cancer cells, Lung Cancer, 68, 355, 10.1016/j.lungcan.2009.07.017

Mehlen, 2006, Metastasis: A question of life or death, Nat. Rev., 6, 449, 10.1038/nrc1886

Kessenbrock, 2010, Matrix metalloproteinases: Regulators of the tumor microenvironment, Cell, 141, 52, 10.1016/j.cell.2010.03.015

Bourboulia, 2010, Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs): Positive and negative regulators in tumor cell adhesion, Semin. Cancer Biol., 20, 161, 10.1016/j.semcancer.2010.05.002

Roy, 2009, Matrix metalloproteinases as novel biomarkers and potential therapeutic targets in human cancer, J. Clin. Oncol., 27, 5287, 10.1200/JCO.2009.23.5556

Stamenkovic, 2000, Matrix metalloproteinases in tumor invasion and metastasis, Semin. Cancer Biol., 10, 415, 10.1006/scbi.2000.0379

Choi, 2013, Saussurea lappa clarke-derived costunolide prevents TNFα-induced breast cancer cell migration and invasion by inhibiting NF-κB activity, Evid. Based Complement. Altern. Med., 9, 362

Kuwano, 1999, Multidrug resistance-associated protein subfamily transporters and drug resistance, Anticancer Drug Des., 14, 123

Allen, 1999, The mouse Bcrp1/Mxr/Abcp gene: Amplification and overexpression in cell lines selected for resistance to ropotecan, mitoxantrone, or doxorubicin, Cancer Res., 59, 4237

Litman, 2001, From MDR to MXR: New understanding of multidrug resistance systems, their properties and clinical significance, Cell. Mol. Life Sci., 58, 931, 10.1007/PL00000912

Fletcher, 2010, ABC transporters in cancer: More than just drug efflux pumps, Nat. Rev. Cancer, 10, 147, 10.1038/nrc2789

Folkman, 1971, Tumor angiogenesis: Therapeutic implication, N. Engl. J. Med., 285, 1182, 10.1056/NEJM197111182852108

Folkman, 1987, Angiogenic factor, Science, 235, 442, 10.1126/science.2432664

Ingber, 1990, Synthetic analogues of fumagillin that inhibit angiogenesis and suppress tumour growth, Nature, 348, 555, 10.1038/348555a0

Jeong, 2002, Costunolide, a sesquiterpene lactone from Saussurea lappa, inhibits the VEGFR KDR/Flk-1 signaling pathway, Cancer Lett., 187, 129, 10.1016/S0304-3835(02)00361-0

Beere, 1993, Differentiation: A suitable strategy for cancer chemotherapy?, Anticancer Drug Des., 8, 299

Pan, 1997, Promotion of HL-60 cell differentiation by 1,25-dihydroxyvitamin D3 regulation of protein kinase C levels and activity, Biochem. Pharmacol., 54, 909, 10.1016/S0006-2952(97)00286-4

Martell, 1988, Effects of protein kinase inhibitors 1(5-isoquinol inesulfonyl)-2-methylpiperazine dihydrochloride (H-7) and N-(2-guanidinoethyl)-5-isoquinolinesulfonamide hydrochloride (HA1004) on calcitriol-induced differentiation of HL-60 cells, Biochem. Pharmacol., 37, 635, 10.1016/0006-2952(88)90136-0

Wu, 1989, Studies on the relationship between protein kinase C and differentiation of human promyelocytic leukemia cells induced by retinoic acid, Leuk. Res., 13, 869, 10.1016/0145-2126(89)90039-8

Choi, 2002, Costunolide induces differentiation of human leukemia HL-60 cells, Arch. Pharm. Res., 25, 480, 10.1007/BF02976606

Kim, 2008, Differential enhancement of leukaemia cell differentiation without elevation of intracellular calcium by plant-derived sesquiterpene lactone compounds, Br. J. Pharmacol., 155, 814, 10.1038/bjp.2008.319

Peng, Z., Wang, Y., Gu, X., Xue, Y., Wu, Q., Zhou, J., and Chan, Y. (2014). Metabolic transformation of breast cancer in a MCF-7 xenograft mouse model and inhibitory effect of volatile oil from Saussurea lappa Decne treatment. Metabolomics.

Hu, 2011, Quantitative analysis of costunolide and dehydrocostuslactone in rat plasma by ultraperformance liquid chromatography–electrospray ionization–mass spectrometry, Biomed. Chromatogr., 25, 547, 10.1002/bmc.1482

Zhang, 2014, Pharmacokinetic study on costunolide and dehydrocostuslactone after oral administration of traditional medicine Aucklandia lappa Decne. by LC/MS/MS, J. Ethnopharmacol., 151, 191, 10.1016/j.jep.2013.10.024

Peng, 2014, Study on the pharmacokinetics andmetabolism of costunolide and dehydrocostus lactone in rats by HPLC-UV and UPLC-Q-TOF/MS, Biomed. Chromatogr., 28, 1325, 10.1002/bmc.3167