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Article

Wedelolactone inhibits breast cancer-induced osteoclastogenesis by decreasing Akt/mTOR signaling

  • Authors:
    • Chia-Jung Hsieh
    • Po-Lin Kuo
    • Ming-Feng Hou
    • Jen-Yu Hung
    • Fang-Rong Chang
    • Ying-Chan Hsu
    • Ya-Fang Huang
    • Eing-Mei Tsai
    • Ya-Ling Hsu
  • View Affiliations / Copyright

    Affiliations: Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan, R.O.C., Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan, R.O.C., School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan, R.O.C., Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 807, Taiwan, R.O.C., Department of Chinese Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan, R.O.C.
  • Pages: 555-562
    |
    Published online on: November 21, 2014
       https://doi.org/10.3892/ijo.2014.2769
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Abstract

The bone is the most common metastatic site of breast cancer. Bone metastasis causes pain, pathologic fractures, and severely reduces the quality of life. Breast cancer causes osteolytic bone metastasis, which is dependent on osteoclast-mediated bone resorption. While current treatments rely on palliative anti-resorptive agents, there is a need to develop a drug based on potential alternative therapies. This study is the first to determine that wedelolactone (WDL), a natural coumarin isolated from plants, can inhibit breast cancer-mediated osteoclastogenesis. Osteoclasts were generated from human CD14+ monocytes cultured with M-CSF/RANKL and WDL suppressed human osteoclast differentiation and activity in vitro in a dose-dependent manner. Moreover, WDL inhibited the upregulation of osteoclasts stimulated by MDA‑MB‑231 breast cancer cells. The activity of WDL on osteoclasts and breast cancer-mediated osteoclastogenesis was associated with the inhibition of Akt/mammalian target of the rapamycin signaling pathway (mTOR). Blocking Akt and mTOR by specific inhibitors significantly decreased osteoclast differentiation and bone resorption. Furthermore, WDL regulated breast cancer-enhanced interaction of osteoblasts and osteoclasts by decreasing M-CSF expression in MDA‑MB‑231-stimulated osteoblasts. Thus, this study suggests that WDL may be a potential natural agent for preventing and treating bone destruction in patients with bone metastasis due to breast cancer.
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1 

Akhtari M, Mansuri J, Newman KA, Guise TM and Seth P: Biology of breast cancer bone metastasis. Cancer Biol Ther. 7:3–9. 2008. View Article : Google Scholar

2 

Rordorf T, Hassan AA, Azim H, et al: Bone health in breast cancer patients: a comprehensive statement by CECOG/SAKK intergroup. Breast. 23:511–525. 2014. View Article : Google Scholar : PubMed/NCBI

3 

Rove KO and Crawford ED: Metastatic cancer in solid tumors and clinical outcome: skeletal-related events. Oncology. 23:21–27. 2009.

4 

Weilbaecher KN, Guise TA and McCauley LK: Cancer to bone: a fatal attraction. Nat Rev Cancer. 11:411–425. 2011. View Article : Google Scholar : PubMed/NCBI

5 

Gupta S, Gupta H, Mandhyan D and Srivastava S: Bisphophonates related osteonecrosis of the jaw. Natl J Maxillofac Surg. 4:151–158. 2013. View Article : Google Scholar

6 

Verron E, Schmid-Antomarchi H, Pascal-Mousselard H, Schmid-Alliana A, Scimeca JC and Bouler JM: Therapeutic strategies for treating osteolytic bone metastases. Drug Discov Today. 19:1419–1426. 2014. View Article : Google Scholar : PubMed/NCBI

7 

Roodman GD: Mechanisms of bone metastasis. N Engl J Med. 350:1655–1664. 2004. View Article : Google Scholar : PubMed/NCBI

8 

Mundy GR: Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer. 2:584–593. 2002. View Article : Google Scholar : PubMed/NCBI

9 

Rodan GA and Martin TJ: Therapeutic approaches to bone diseases. Science. 289:1508–1514. 2000. View Article : Google Scholar : PubMed/NCBI

10 

Suda T, Takahashi N, Udagawa N, Jimi E, Gillespie MT and Martin TJ: Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocr Rev. 20:345–357. 1999. View Article : Google Scholar : PubMed/NCBI

11 

Lee ZH and Kim HH: Signal transduction by receptor activator of nuclear factor kappa B in osteoclasts. Biochem Biophys Res Commun. 305:211–214. 2003. View Article : Google Scholar : PubMed/NCBI

12 

Chen YC, Sosnoski DM and Mastro AM: Breast cancer metastasis to the bone: mechanisms of bone loss. Breast Cancer Res. 12:2152010. View Article : Google Scholar : PubMed/NCBI

13 

Mountzios G, Dimopoulos MA, Bamias A, et al: Abnormal bone remodeling process is due to an imbalance in the receptor activator of nuclear factor-kappaB ligand (RANKL)/osteoprotegerin (OPG) axis in patients with solid tumors metastatic to the skeleton. Acta Oncol. 46:221–229. 2007. View Article : Google Scholar : PubMed/NCBI

14 

McGrath EE: OPG/RANKL/RANK pathway as a therapeutic target in cancer. J Thorac Oncol. 6:1468–1473. 2011. View Article : Google Scholar : PubMed/NCBI

15 

Azim HA, Kamal NS and Azim HA Jr: Bone metastasis in breast cancer: the story of RANK-ligand. J Egypt Nat Cancer Inst. 24:107–114. 2012. View Article : Google Scholar : PubMed/NCBI

16 

Patel M, Kadakia V and Mishra S: Simultaneous estimation of andrographolide and wedelolactone in herbal formulations. Indian J Pharm Sci. 70:6892008. View Article : Google Scholar : PubMed/NCBI

17 

Roy RK, Thakur M and Dixit VK: Hair growth promoting activity of Eclipta alba in male albino rats. Arch Dermatol Res. 300:357–364. 2008. View Article : Google Scholar : PubMed/NCBI

18 

Singh B, Saxena AK, Chandan BK, Agarwal SG and Anand KK: In vivo hepatoprotective activity of active fraction from ethanolic extract of Eclipta alba leaves. Indian J Physiol Pharmacol. 45:435–441. 2001.

19 

Wagner H, Geyer B, Kiso Y, Hikino H and Rao GS: Coumestans as the main active principles of the liver drugs Eclipta alba and Wedelia calendulacea. Planta Med. 370–374. 1986. View Article : Google Scholar : PubMed/NCBI

20 

Lin FM, Chen LR, Lin EH, et al: Compounds from Wedelia chinensis synergistically suppress androgen activity and growth in prostate cancer cells. Carcinogenesis. 28:2521–2529. 2007. View Article : Google Scholar : PubMed/NCBI

21 

Tewtrakul S, Subhadhirasakul S, Cheenpracha S and Karalai C: HIV-1 protease and HIV-1 integrase inhibitory substances from Eclipta prostrata. Phytother Res. 21:1092–1095. 2007. View Article : Google Scholar : PubMed/NCBI

22 

Tsai CH, Lin FM, Yang YC, et al: Herbal extract of Wedelia chinensis attenuates androgen receptor activity and orthotopic growth of prostate cancer in nude mice. Clin Cancer Res. 15:5435–5444. 2009. View Article : Google Scholar : PubMed/NCBI

23 

Vender JR, Laird MD and Dhandapani KM: Inhibition of NFkappaB reduces cellular viability in GH3 pituitary adenoma cells. Neurosurgery. 62:1122–1128. 2008. View Article : Google Scholar : PubMed/NCBI

24 

Idris AI, Libouban H, Nyangoga H, Landao-Bassonga E, Chappard D and Ralston SH: Pharmacologic inhibitors of IkappaB kinase suppress growth and migration of mammary carcinosarcoma cells in vitro and prevent osteolytic bone metastasis in vivo. Mol Cancer Ther. 8:2339–2347. 2009. View Article : Google Scholar : PubMed/NCBI

25 

Sarveswaran S, Gautam SC and Ghosh J: Wedelolactone, a medicinal plant-derived coumestan, induces caspase-dependent apoptosis in prostate cancer cells via downregulation of PKCɛ without inhibiting Akt. Int J Oncol. 41:2191–2199. 2012.PubMed/NCBI

26 

Sterling JA, Edwards JR, Martin TJ and Mundy GR: Advances in the biology of bone metastasis: how the skeleton affects tumor behavior. Bone. 48:6–15. 2011. View Article : Google Scholar

27 

Furugaki K, Moriya Y, Iwai T, et al: Erlotinib inhibits osteolytic bone invasion of human non-small-cell lung cancer cell line NCI-H292. Clin Exp Metastasis. 28:649–659. 2011. View Article : Google Scholar : PubMed/NCBI

28 

Hsu YL, Huang MS, Yang CJ, Hung JY, Wu LY and Kuo PL: Lung tumor-associated osteoblast-derived bone morphogenetic protein-2 increased epithelial-to-mesenchymal transition of cancer by Runx2/Snail signaling pathway. J Biol Chem. 286:37335–37346. 2011. View Article : Google Scholar : PubMed/NCBI

29 

Takayanagi H: New immune connections in osteoclast formation. Ann NY Acad Sci. 192:117–123. 2010. View Article : Google Scholar

30 

Yoneda T, Tanaka S and Hata K: Role of RANKL/RANK in primary and secondary breast cancer. World J Orthop. 4:178–185. 2013. View Article : Google Scholar : PubMed/NCBI

31 

Skeen JE, Bhaskar PT, Chen CC, et al: Akt deficiency impairs normal cell proliferation and suppresses oncogenesis in a p53-independent and mTORC1-dependent manner. Cancer Cell. 10:269–280. 2006. View Article : Google Scholar : PubMed/NCBI

32 

Moon JB, Kim JH, Kim K, et al: Akt induces osteoclast differentiation through regulating the GSK3β/NFATc1 signaling cascade. J Immunol. 188:163–169. 2012. View Article : Google Scholar

33 

Cao H, Zhu K, Qiu L, et al: Critical role of AKT protein in myeloma-induced osteoclast formation and osteolysis. J Biol Chem. 288:30399–30410. 2013. View Article : Google Scholar : PubMed/NCBI

34 

Sugatani T and Hruska KA: Akt1/Akt2 and mammalian target of rapamycin/Bim play critical roles in osteoclast differentiation and survival, respectively, whereas Akt is dispensable for cell survival in isolated osteoclast precursors. J Biol Chem. 280:3583–3589. 2005. View Article : Google Scholar

35 

Sanchez CP and He YZ: Bone growth during rapamycin therapy in young rats. BMC Pediatr. 9:32009. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Hsieh C, Kuo P, Hou M, Hung J, Chang F, Hsu Y, Huang Y, Tsai E and Hsu Y: Wedelolactone inhibits breast cancer-induced osteoclastogenesis by decreasing Akt/mTOR signaling. Int J Oncol 46: 555-562, 2015.
APA
Hsieh, C., Kuo, P., Hou, M., Hung, J., Chang, F., Hsu, Y. ... Hsu, Y. (2015). Wedelolactone inhibits breast cancer-induced osteoclastogenesis by decreasing Akt/mTOR signaling. International Journal of Oncology, 46, 555-562. https://doi.org/10.3892/ijo.2014.2769
MLA
Hsieh, C., Kuo, P., Hou, M., Hung, J., Chang, F., Hsu, Y., Huang, Y., Tsai, E., Hsu, Y."Wedelolactone inhibits breast cancer-induced osteoclastogenesis by decreasing Akt/mTOR signaling". International Journal of Oncology 46.2 (2015): 555-562.
Chicago
Hsieh, C., Kuo, P., Hou, M., Hung, J., Chang, F., Hsu, Y., Huang, Y., Tsai, E., Hsu, Y."Wedelolactone inhibits breast cancer-induced osteoclastogenesis by decreasing Akt/mTOR signaling". International Journal of Oncology 46, no. 2 (2015): 555-562. https://doi.org/10.3892/ijo.2014.2769
Copy and paste a formatted citation
x
Spandidos Publications style
Hsieh C, Kuo P, Hou M, Hung J, Chang F, Hsu Y, Huang Y, Tsai E and Hsu Y: Wedelolactone inhibits breast cancer-induced osteoclastogenesis by decreasing Akt/mTOR signaling. Int J Oncol 46: 555-562, 2015.
APA
Hsieh, C., Kuo, P., Hou, M., Hung, J., Chang, F., Hsu, Y. ... Hsu, Y. (2015). Wedelolactone inhibits breast cancer-induced osteoclastogenesis by decreasing Akt/mTOR signaling. International Journal of Oncology, 46, 555-562. https://doi.org/10.3892/ijo.2014.2769
MLA
Hsieh, C., Kuo, P., Hou, M., Hung, J., Chang, F., Hsu, Y., Huang, Y., Tsai, E., Hsu, Y."Wedelolactone inhibits breast cancer-induced osteoclastogenesis by decreasing Akt/mTOR signaling". International Journal of Oncology 46.2 (2015): 555-562.
Chicago
Hsieh, C., Kuo, P., Hou, M., Hung, J., Chang, F., Hsu, Y., Huang, Y., Tsai, E., Hsu, Y."Wedelolactone inhibits breast cancer-induced osteoclastogenesis by decreasing Akt/mTOR signaling". International Journal of Oncology 46, no. 2 (2015): 555-562. https://doi.org/10.3892/ijo.2014.2769
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