Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende
Erweiterte Suche
Anmelden
nach oben
Breast Cancer Research and Treatment
Erschienen in: Breast Cancer Research and Treatment 1/2014

01.02.2014 | Preclinical study

Andrographolide prevents human breast cancer-induced osteoclastic bone loss via attenuated RANKL signaling

verfasst von: Zanjing Zhai, Xinhua Qu, Wei Yan, Haowei Li, Guangwang Liu, Xuqiang Liu, Tingting Tang, An Qin, Kerong Dai

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 1/2014

Einloggen, um Zugang zu erhalten

Abstract

Bone metastasis is a common and serious complication in advanced cancers such as breast cancer, prostate cancer, and multiple myeloma. Agents that prevent bone loss could be used to develop an alternative therapy for bone metastasis. RANKL, a member of the tumor necrosis factor superfamily, has been shown to play a significant role in cancer-associated bone loss. In this study, we examined the efficacy of the natural compound andrographolide (AP), a diterpenoid lactone isolated from the traditional Chinese and Indian medicinal plant Andrographis paniculata, in reducing breast cancer-induced osteolysis. AP prevented human breast cancer-induced bone loss by suppressing RANKL-mediated and human breast cancer cell-induced osteoclast differentiation. Molecular analysis revealed that AP prevented osteoclast function by inhibiting RANKL-induced NF-κB and ERK signaling pathway in lower dose (20 μM), as well as inducing apoptosis at higher dose (40 μM). Thus, AP is a potent inhibitor of breast cancer-induced bone metastasis.
Literatur
1.
Coleman R (2001) Metastatic bone disease: clinical features, pathophysiology and treatment strategies. Cancer Treat Rev 27:165–176PubMedCrossRef
2.
3.
4.
Mundy GR (2002) Metastasis: metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer 2:584–593PubMedCrossRef
5.
Roodman GD, Dougall WC (2008) RANK ligand as a therapeutic target for bone metastases and multiple myeloma. Cancer Treat Rev 34:92–101PubMedCrossRef
6.
Bhatia P, Sanders MM, Hansen MF (2005) Expression of receptor activator of nuclear factor-kappaB is inversely correlated with metastatic phenotype in breast carcinoma. Clin Cancer Res 11:162–165PubMed
7.
De Leenheer E, Mueller GS, Vanderkerken K, Croucher PI (2004) Evidence of a role for RANKL in the development of myeloma bone disease. Curr Opin Pharmacol 4:340–346PubMedCrossRef
8.
Farrugia AN, Atkins GJ, To LB, Pan B, Horvath N, Kostakis P, Findlay DM, Bardy P, Zannettino AC (2003) Receptor activator of nuclear factor-κB ligand expression by human myeloma cells mediates osteoclast formation in vitro and correlates with bone destruction in vivo. Cancer Res 63:5438–5445PubMed
9.
Keller ET, Brown J (2004) Prostate cancer bone metastases promote both osteolytic and osteoblastic activity. J Cell Biochem 91:718–729PubMedCrossRef
10.
Boyle WJ, Simonet WS, Lacey DL (2003) Osteoclast differentiation and activation. Nature 423:337–342PubMedCrossRef
11.
12.
Kurata T, Nakagawa K (2012) Efficacy and safety of denosumab for the treatment of bone metastases in patients with advanced cancer. Jpn J Clin Oncol 42:663–669PubMedCrossRef
13.
Lipton A, Balakumaran A (2012) Denosumab for the treatment of cancer therapy-induced bone loss and prevention of skeletal-related events in patients with solid tumors. Expert Rev Clin Pharmacol 5:359–371PubMedCrossRef
14.
Mackiewicz-Wysocka M, Pankowska M, Wysocki PJ (2012) Progress in the treatment of bone metastases in cancer patients. Expert Opin Invest Drugs 21:785–795CrossRef
15.
Paller CJ, Carducci MA, Philips GK (2012) Management of bone metastases in refractory prostate cancer–role of denosumab. Clin Interv Aging 7:363PubMedCentralPubMedCrossRef
16.
Hillner BE, Ingle JN, Berenson JR, Janjan NA, Albain KS, Lipton A, Yee G, Biermann JS, Chlebowski RT, Pfister DG (2000) American society of clinical oncology guideline on the role of bisphosphonates in breast cancer. J Clin Oncol 18:1378–1391PubMed
17.
Ernst E (2004) Andrographis paniculata in the treatment of upper respiratory tract infections: a systematic review of safety and efficacy. Planta Med 70:293–298PubMedCrossRef
18.
Melchior J, Palm S, Wikman G (1997) Controlled clinical study of standardized Andrographis paniculata extract in common cold: a pilot trial. Phytomedicine 3:315–318PubMedCrossRef
19.
Negi AS, Kumar J, Luqman S, Shanker K, Gupta M, Khanuja S (2008) Recent advances in plant hepatoprotectives: a chemical and biological profile of some important leads. Med Res Rev 28:746–772PubMedCrossRef
20.
Puri A, Saxena R, Saxena R, Saxena K, Srivastava V, Tandon J (1993) Immunostimulant agents from Andrographis paniculata. J Nat Prod 56:995–999PubMedCrossRef
21.
Roxas M, Jurenka J (2007) Colds and influenza: a review of diagnosis and conventional, botanical, and nutritional considerations. Altern Med Rev 12:25–48PubMed
22.
Thamlikitkul V, Dechatiwongse T, Theerapong S, Chantrakul C, Boonroj P, Punkrut W, Ekpalakorn W, Boontaeng N, Taechaiya S, Petcharoen S (1991) Efficacy of Andrographis paniculata, Nees for pharyngotonsillitis in adults. J Med Assoc Thai 74:437PubMed
23.
Zhi-ling G, Hua-yue Z, Xin-hua Z (1995) An experimental study of the mechanism of andrographis paniculata nees (APN) in alleviating the Ca(2+)-overloading in the process of myocardial ischemie reperfusion. J Tongji Med Univ 15:205–208CrossRef
24.
Rajagopal S, Kumar RA, Deevi DS, Satyanarayana C, Rajagopalan R (2003) Andrographolide, a potential cancer therapeutic agent isolated from Andrographis paniculata. J Exp Ther Oncol 3:147–158PubMedCrossRef
25.
Wang L-J, Zhou X, Wang W, Tang F, Qi C-L, Yang X, Wu S, Lin Y-Q, Wang J-T, Geng J-G (2011) Andrographolide inhibits oral squamous cell carcinogenesis through NF-κB inactivation. J Dent Res 90:1246–1252PubMedCrossRef
26.
Chen H-W, Lin A-H, Chu H-C, Li C-C, Tsai C-W, Chao C-Y, Wang C-J, Lii C-K, Liu K-L (2011) Inhibition of TNF-α-induced inflammation by andrographolide via down-regulation of the PI3K/Akt signaling pathway. J Nat Prod 74:2408–2413PubMedCrossRef
27.
Chiou WF, Lin JJ, Chen CF (1998) Andrographolide suppresses the expression of inducible nitric oxide synthase in macrophage and restores the vasoconstriction in rat aorta treated with lipopolysaccharide. Br J Pharmacol 125:327–334PubMedCrossRef
28.
Shen YC, Chen CF, Chiou WF (2002) Andrographolide prevents oxygen radical production by human neutrophils: possible mechanism (s) involved in its anti-inflammatory effect. Br J Pharmacol 135:399–406PubMedCrossRef
29.
Handa S, Sharma A (1990) Hepatoprotective activity of andrographolide against galactosamine and paracetamol intoxication in rats. Indian J Med Res 92:284PubMed
30.
Trivedi NP, Rawal UM, Patel BP (2009) Potency of andrographolide as an antitumor compound in BHC-induced liver damage. Integr Cancer Ther 8:177–189PubMedCrossRef
31.
Jiang X, Yu P, Jiang J, Zhang Z, Wang Z, Yang Z, Tian Z, Wright SC, Larrick JW, Wang Y (2009) Synthesis and evaluation of antibacterial activities of andrographolide analogues. Eur J Med Chem 44:2936–2943PubMedCrossRef
32.
Miller FR, Santner SJ, Tait L, Dawson PJ (2000) MCF10DCIS. com xenograft model of human comedo ductal carcinoma in situ. J Natl Cancer Inst 92:1185–1186PubMedCrossRef
33.
Nangia-Makker P, Raz T, Tait L, Shekhar MP, Li H, Balan V, Makker H, Fridman R, Maddipati K, Raz A (2013) Ocimum gratissimum retards breast cancer growth and progression and is a natural inhibitor of matrix metalloproteases. Cancer Biol Ther 14:1CrossRef
34.
Nangia-Makker P, Tait L, Shekhar MP, Palomino E, Hogan V, Piechocki MP, Funasaka T, Raz A (2007) Inhibition of breast tumor growth and angiogenesis by a medicinal herb: Ocimum gratissimum. Int J Cancer 121:884–894PubMedCentralPubMedCrossRef
35.
Tait LR, Pauley RJ, Santner SJ, Heppner GH, Heng HH, Rak JW, Miller FR (2007) Dynamic stromal-epithelial interactions during progression of MCF10DCIS. com xenografts. Int J Cancer 120:2127–2134PubMedCrossRef
36.
Hsu H, Lacey DL, Dunstan CR, Solovyev I, Colombero A, Timms E, Tan H-L, Elliott G, Kelley MJ, Sarosi I (1999) Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand. Proc Natl Acad Sci USA 96:3540–3545PubMedCrossRef
37.
Qin A, Cheng TS, Lin Z, Cao L, Chim SM, Pavlos NJ, Xu J, Zheng MH, Dai KR (2012) Prevention of wear particle-induced osteolysis by a novel V-ATPase inhibitor saliphenylhalamide through inhibition of osteoclast bone resorption. PLoS One 7:e34132PubMedCentralPubMedCrossRef
38.
Wang C, Steer JH, Joyce DA, Yip KH, Zheng MH, Xu J (2003) 12-O-tetradecanoylphorbol-13-acetate (TPA) inhibits osteoclastogenesis by suppressing RANKL-induced NF-κB activation. J Bone Miner Res 18:2159–2168PubMedCrossRef
39.
Akama KT, Albanese C, Pestell RG, Van Eldik LJ (1998) Amyloid beta-peptide stimulates nitric oxide production in astrocytes through an NF-κB-dependent mechanism. Proc Natl Acad Sci USA 95:5795–5800PubMedCrossRef
40.
Steer JH, Kroeger KM, Abraham LJ, Joyce DA (2000) Glucocorticoids suppress tumor necrosis factor-alpha expression by human monocytic THP-1 cells by suppressing transactivation through adjacent NF-kappaB and c-Jun-activating transcription factor-2 binding sites in the promoter. J Biol Chem 275:18432–18440. doi:10.​1074/​jbc.​M906304199 PubMedCrossRef
41.
Wedemeyer C, Xu J, Neuerburg C, Landgraeber S, Malyar NM, von Knoch F, Gosheger G, von Knoch M, Löer F, Saxler G (2007) Particle-induced osteolysis in three-dimensional micro-computed tomography. Calcif Tissue Int 81:394–402PubMedCrossRef
42.
Chikatsu N, Takeuchi Y, Tamura Y, Fukumoto S, Yano K, Tsuda E, Ogata E, Fujita T (2000) Interactions between cancer and bone marrow cells induce osteoclast differentiation factor expression and osteoclast-like cell formation in vitro. Biochem Biophys Res Commun 267:632–637PubMedCrossRef
43.
Franzoso G, Carlson L, Xing L, Poljak L, Shores EW, Brown KD, Leonardi A, Tran T, Boyce BF, Siebenlist U (1997) Requirement for NF-kappaB in osteoclast and B-cell development. Genes Dev 11:3482–3496PubMedCrossRef
44.
Soysa N, Alles N (2009) NF-κB functions in osteoclasts. Biochem Biophys Res Commun 378:1–5PubMedCrossRef
45.
DiDonato JA, Hayakawa M, Rothwarf DM, Zandi E, Karin M (1997) A cytokine-responsive IκB kinase that activates the transcription factor NF-κB. Nature 388:548–554PubMedCrossRef
46.
Monje P, Hernández-Losa J, Lyons RJ, Castellone MD, Gutkind JS (2005) Regulation of the transcriptional activity of c-Fos by ERK A novel role for the prolyl isomerase PIN1. J Biol Chem 280:35081–35084PubMedCrossRef
47.
Ang E, Liu Q, Qi M, Liu HG, Yang X, Chen H, Zheng MH, Xu J (2011) Mangiferin attenuates osteoclastogenesis, bone resorption, and RANKL-induced activation of NF-κB and ERK. J Cell Biochem 112:89–97PubMedCrossRef
48.
Kim HJ, Lee Y, Chang E-J, Kim H-M, Hong S-P, Lee ZH, Ryu J, Kim H-H (2007) Suppression of osteoclastogenesis by N,N-dimethyl-d-erythro-sphingosine: a sphingosine kinase inhibition-independent action. Mol Pharmacol 72:418–428PubMedCrossRef
49.
Ikeda F, Nishimura R, Matsubara T, Tanaka S, Inoue J-I, Reddy SV, Hata K, Yamashita K, Hiraga T, Watanabe T (2004) Critical roles of c-Jun signaling in regulation of NFAT family and RANKL-regulated osteoclast differentiation. J Clin Invest 114:475–484PubMedCentralPubMedCrossRef
50.
Matsumoto M, Sudo T, Saito T, Osada H, Tsujimoto M (2000) Involvement of p38 mitogen-activated protein kinase signaling pathway in osteoclastogenesis mediated by receptor activator of NF-κB ligand (RANKL). J Biol Chem 275:31155–31161PubMedCrossRef
51.
David J-P, Sabapathy K, Hoffmann O, Idarraga MH, Wagner EF (2002) JNK1 modulates osteoclastogenesis through both c-Jun phosphorylation-dependent and-independent mechanisms. J Cell Sci 115:4317–4325PubMedCrossRef
52.
Lee J-H, Jin H, Shim H-E, Kim H-N, Ha H, Lee ZH (2010) Epigallocatechin-3-gallate inhibits osteoclastogenesis by down-regulating c-Fos expression and suppressing the nuclear factor-κB signal. Mol Pharmacol 77:17–25PubMedCrossRef
53.
Lee S, Woo K, Kim S, Kim H-M, Kwack K, Lee Z, Kim H-H (2002) The phosphatidylinositol 3-kinase, p38, and extracellular signal-regulated kinase pathways are involved in osteoclast differentiation. Bone 30:71–77PubMedCrossRef
54.
55.
56.
Pahl HL (1999) Activators and target genes of Rel/NF-kappaB transcription factors. Oncogene 18:6853PubMedCrossRef
57.
Chen C-L, Lin C-F, Wan S-W, Wei L-S, Chen M-C, Yeh T-M, Liu H-S, Anderson R, Lin Y-S (2013) Anti-dengue virus nonstructural protein 1 antibodies cause NO-mediated endothelial cell apoptosis via ceramide-regulated glycogen synthase kinase-3β and NF-κB activation. J Immunol 191:1744–1752PubMedCrossRef
58.
Ghosh Sankar KM (2002) Missing pieces in the NF-kappaB puzzle. Cell 109(Suppl):81–96CrossRef
59.
Puszynski K, Bertolusso R, Lipniacki T (2009) Crosstalk between p53 and nuclear factor-κB systems: pro-and anti-apoptotic functions of NF-κB. IET Syst Biol 3:356–367PubMedCrossRef
60.
Radhakrishnan SK, Kamalakaran S (2006) Pro-apoptotic role of NF-κB: implications for cancer therapy. Biochim Biophys Acta 1766:53–62PubMed
61.
Cory S, Adams JM (2002) The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer 2:647–656PubMedCrossRef
62.
Emoto Y, Manome Y, Meinhardt G, Kisaki H, Kharbanda S, Robertson M, Ghayur T, Wong W, Kamen R, Weichselbaum R (1995) Proteolytic activation of protein kinase C delta by an ICE-like protease in apoptotic cells. EMBO J 14:6148PubMed
63.
Porter AG, Jänicke RU (1999) Emerging roles of caspase-3 in apoptosis. Cell Death Differ 6:99PubMedCrossRef
64.
Xue D, Shaham S, Horvitz HR (1996) The Caenorhabditis elegans cell-death protein CED-3 is a cysteine protease with substrate specificities similar to those of the human CPP32 protease. Genes Dev 10:1073–1083PubMedCrossRef
65.
Garcia M, Jemal A, Ward E, Center M, Hao Y, Siegel R, Thun M (2007) Global cancer facts and figures 2007. American Cancer Society, Atlanta
66.
Society AC (2007) Breast cancer facts and figures 2007–2008. American Cancer Society, Atlanta
67.
68.
69.
Costa L, Major PP (2009) Effect of bisphosphonates on pain and quality of life in patients with bone metastases. Nat Clin Pract Oncol 6:163–174PubMedCrossRef
70.
Body J (2002) Calcitonin for the long-term prevention and treatment of postmenopausal osteoporosis. Bone 30:75SPubMedCrossRef
71.
72.
73.
Tremollieres F, Lopes P (2002) Specific estrogen receptor modulators (SERMs). Presse Med 31(28):1323–1328PubMed
74.
Watts NB (2003) Bisphosphonate treatment of osteoporosis. Clin Geriatr Med 19(2):395–414
75.
Wood AJJ, Eastell R (1998) Treatment of postmenopausal osteoporosis. N Engl J Med 338:736–746CrossRef
76.
Mariotti A (2008) Bisphosphonates and osteonecrosis of the jaws. J Dent Educ 72:919–929PubMed
77.
Gevorgyan A, Enepekides DJ (2008) Bisphosphonate-induced necrosis of the jaws: a reconstructive nightmare. Curr Opin Otolaryngol Head Neck Surg 16:325–330PubMedCrossRef
78.
79.
Canon J, Bryant R, Roudier M, Osgood T, Jones J, Miller R, Coxon A, Radinsky R, Dougall WC (2010) Inhibition of RANKL increases the anti-tumor effect of the EGFR inhibitor panitumumab in a murine model of bone metastasis. Bone 46:1613–1619PubMedCrossRef
80.
Canon JR, Roudier M, Bryant R, Morony S, Stolina M, Kostenuik PJ, Dougall WC (2008) Inhibition of RANKL blocks skeletal tumor progression and improves survival in a mouse model of breast cancer bone metastasis. Clin Exp Metastasis 25:119–129PubMedCrossRef
81.
Morony S, Capparelli C, Sarosi I, Lacey DL, Dunstan CR, Kostenuik PJ (2001) Osteoprotegerin inhibits osteolysis and decreases skeletal tumor burden in syngeneic and nude mouse models of experimental bone metastasis. Cancer Res 61:4432–4436PubMed
82.
Teitelbaum SL, Ross FP (2003) Genetic regulation of osteoclast development and function. Nat Rev Genet 4:638–649PubMedCrossRef
83.
Iotsova V, Caamaño J, Loy J, Yang Y, Lewin A, Bravo R (1997) Osteopetrosis in mice lacking NF-κB1 and NF-κB2. Nat Med 3:1285–1289PubMedCrossRef
84.
Xing L, Bushnell TP, Carlson L, Tai Z, Tondravi M, Siebenlist U, Young F, Boyce BF (2002) NF-kappaB p50 and p52 expression is not required for RANK-expressing osteoclast progenitor formation but is essential for RANK- and cytokine-mediated osteoclastogenesis. J Bone Miner Res 17:1200–1210. doi:10.​1359/​jbmr.​2002.​17.​7.​1200 PubMedCrossRef
85.
Ruocco MG, Karin M (2007) Control of osteoclast activity and bone loss by IKK subunits: new targets for therapy. Adv Exp Med Biol 602:125–134PubMedCrossRef
86.
Ruocco MG, Maeda S, Park JM, Lawrence T, Hsu L-C, Cao Y, Schett G, Wagner EF, Karin M (2005) IκB kinase (IKK) β, but not IKKα, is a critical mediator of osteoclast survival and is required for inflammation-induced bone loss. J Exp Med 201:1677–1687PubMedCentralPubMedCrossRef
87.
Lee ZH, Kim H-H (2003) Signal transduction by receptor activator of nuclear factor kappaB in osteoclasts. Biochem Biophys Res Commun 305:211–214PubMedCrossRef
88.
Biswas DK, Shi Q, Baily S, Strickland I, Ghosh S, Pardee AB, Iglehart JD (2004) NF-κB activation in human breast cancer specimens and its role in cell proliferation and apoptosis. Proc Natl Acad Sci USA 101:10137–10142PubMedCrossRef
Metadaten
Titel
Andrographolide prevents human breast cancer-induced osteoclastic bone loss via attenuated RANKL signaling
verfasst von
Zanjing Zhai
Xinhua Qu
Wei Yan
Haowei Li
Guangwang Liu
Xuqiang Liu
Tingting Tang
An Qin
Kerong Dai
Publikationsdatum
01.02.2014
Verlag
Springer US
Erschienen in
Breast Cancer Research and Treatment / Ausgabe 1/2014
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-014-2844-7

Weitere Artikel der Ausgabe 1/2014

Breast Cancer Research and Treatment 1/2014 Zur Ausgabe

Preclinical study

Risk of lymphedema after mastectomy: potential benefit of applying ACOSOG Z0011 protocol to mastectomy patients

Clinical trial

Body fat composition impacts the hematologic toxicities and pharmacokinetics of doxorubicin in Asian breast cancer patients

Clinical trial

Pure anti-tumor effect of zoledronic acid in naïve bone-only metastatic and locally advanced breast cancer: proof from the “biological window therapy”

Preclinical Study

Diallyl trisulfide inhibits estrogen receptor-α activity in human breast cancer cells

Clinical trial

Response and prognosis after neoadjuvant chemotherapy in 1,051 patients with infiltrating lobular breast carcinoma

Review

Shoulder and arm morbidity in sentinel node-negative breast cancer patients: a systematic review

Neu im Fachgebiet Onkologie

25.04.2024 | Nierenkarzinom | Nachrichten

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 | NSCLC | Nachrichten

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

24.04.2024 | DGIM 2024 | Nachrichten

Bei Senioren mit Prostatakarzinom auf Anämie achten!

23.04.2024 | Medikamente in Schwangerschaft und Stillzeit | Nachrichten

ICI-Therapie in der Schwangerschaft wird gut toleriert
weitere anzeigen

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen