twitter

Friday, 20 February 2015

Plant-derived anticancer agents: a promising treatment for bone metastasis



Plant-derived anticancer agents: a promising treatment for bone metastasis

BoneKEy Reports
(2014)
3,
Article number:
599
doi:10.1038/bonekey.2014.94
Received
Accepted
Published online

Abstract


Bone metastasis is a very frequent complication of advanced cancer, and it remains an incurable disease. Current therapies that have been approved for the treatment of bone metastases delay the occurrence of skeletal-related events and can extend the patient’s lifespan by a few years. However, they will not cure or cause the regression of established bone metastases, and new side effects are emerging after prolonged treatment. Thus, new therapies are severely needed. There are compelling evidences from in vitro and in vivo preclinical studies that support the use of compounds derived from plants to treat several forms of cancers including bone metastasis. More than 25% of the drugs used during the past 20 years were directly derived from plants, whereas another 25% are chemically altered natural products. Still, only 5–15% of the ~250 000 higher plants have ever been investigated for bioactive compounds. There is a growing interest for the study of anticancer drugs with relatively low side effects that target specific key signaling pathways that control the establishment and progression of the cancer metastasis. Therefore, further studies are needed to identify new natural compounds with high efficiency in cancer prevention and treatment. Extensive reviews about plant-derived agents and their use in cancer have been published, but none when it comes to the treatment of bone metastases. Only a few of these compounds have been evaluated for the treatment of bone metastasis; here we describe some of the most prominent ones that are having the potential to reach the clinic soon.

References



  1. Newman DJ, Cragg GM, Holbeck S, Sausville EA. Natural products and derivatives as leads to cell cycle pathway targets in cancer chemotherapy. Curr Cancer Drug Targets 2002;2:279–308.
  2. Balunas MJ, Kinghorn AD. Drug discovery from medicinal plants. Life Sci 2005;78:431–441.
  3. van Der Heijden R, Jacobs DI, Snoeijer W, Hallard D, Verpoorte R. The Catharanthus alkaloids: pharmacognosy and biotechnology. Curr Med Chem 2004;11:607–628.
  4. Gordaliza M, Castro MA, del Corral JM, Feliciano AS. Antitumor properties of podophyllotoxin and related compounds. Curr Pharm Des 2000;6:1811–1839.
  5. Oberlies NH, Kroll DJ. Camptothecin and taxol: historic achievements in natural products research. J Nat Prod 2004;67:129–135.
  6. Palombo EA. Phytochemicals from traditional medicinal plants used in the treatment of diarrhoea: modes of action and effects on intestinal function. Phytother Res 2006;20:717–724.
  7. Roodman GD. Mechanisms of bone metastasis. N Engl J Med 2004;350:1655–1664.
  8. Mundy GR. Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer 2002;2:584–593.
  9. Weilbaecher KN, Guise TA, McCauley LK. Cancer to bone: a fatal attraction. Nat Rev Cancer 2011;11:411–425.
  10. Ibrahim A, Scher N, Williams G, Sridhara R, Li N, Chen G et al. Approval summary for zoledronic acid for treatment of multiple myeloma and cancer bone metastases. Clin Cancer Res 2003;9:2394–2399 2003.
  11. Clezardin P. Potential anticancer properties of bisphosphonates: insights from preclinical studies. Anticancer Agents Med Chem 2012;12:102–113.
  12. Clezardin P, Fournier P, Boissier S, Peyruchaud O. In vitro and in vivo antitumor effects of bisphosphonates. Curr Med Chem 2003;10:173–180.
  13. Woo SB, Hellstein JW, Kalmar JR. Narrative [corrected] review: bisphosphonates and osteonecrosis of the jaws. Ann Intern Med 2006;144:753–761.
  14. Perazella MA, Markowitz GS. Bisphosphonate nephrotoxicity. Kidney Int 2008;74:1385–1393.
  15. Sandur SK, Pandey MK, Sung B, Aggarwal BB. 5-Hydroxy-2-methyl-1,4-naphthoquinone, a vitamin K3 analogue, suppresses STAT3 activation pathway through induction of protein tyrosine phosphatase, SHP-1: potential role in chemosensitization. Mol Cancer Res 2010;8:107–118.
  16. Hsu YL, Cho CY, Kuo PL, Huang YT, Lin CC. Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) induces apoptosis and cell cycle arrest in A549 cells through p53 accumulation via c-Jun NH2-terminal kinase-mediated phosphorylation at serine 15 in vitro and in vivo. J Pharmacol Exp Ther 2006;318:484–494.
  17. Manu KA, Shanmugam MK, Rajendran P, Li F, Ramachandran L, Hay HS et al. Plumbagin inhibits invasion and migration of breast and gastric cancer cells by downregulating the expression of chemokine receptor CXCR4. Mol Cancer 2011;10:107.
  18. Sand JM, Bin Hafeez B, Jamal MS, Witkowsky O, Siebers EM, Fischer J et al. Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone), isolated from Plumbago zeylanica, inhibits ultraviolet radiation-induced development of squamous cell carcinomas. Carcinogenesis 2012;33:184–190.
  19. Sun J, McKallip RJ. Plumbagin treatment leads to apoptosis in human K562 leukemia cells through increased ROS and elevated TRAIL receptor expression. Leuk Res 2011;35:1402–1408.
  20. Padhye S, Dandawate P, Yusufi M, Ahmad A, Sarkar FH. Perspectives on medicinal properties of plumbagin and its analogs. Med Res Rev 2012;32:1131–1158.
  21. Sinha S, Pal K, Elkhanany A, Dutta S, Cao Y, Mondal G et al. Plumbagin inhibits tumorigenesis and angiogenesis of ovarian cancer cells in vivo. Int J Cancer 2013;132:1201–1212.
  22. Chen CA, Chang HH, Kao CY, Tsai TH, Chen YJ. Plumbagin, isolated from Plumbago zeylanica, induces cell death through apoptosis in human pancreatic cancer cells. Pancreatology 2009;9:797–809.
  23. Shieh JM, Chiang TA, Chang WT, Chao CH, Lee YC, Huang GY et al. Plumbagin inhibits TPA-induced MMP-2 and u-PA expressions by reducing binding activities of NF-kappaB and AP-1 via ERK signaling pathway in A549 human lung cancer cells. Mol Cell Biochem 2010;335:181–193.
  24. Hafeez BB, Zhong W, Fischer JW, Mustafa A, Shi X, Meske L et al. Plumbagin, a medicinal plant (Plumbago zeylanica)-derived 1,4-naphthoquinone, inhibits growth and metastasis of human prostate cancer PC-3 M-luciferase cells in an orthotopic xenograft mouse model. Mol Oncol 2013;7:428–439.
  25. Srinivas P, Gopinath G, Banerji A, Dinakar A, Srinivas G. Plumbagin induces reactive oxygen species, which mediate apoptosis in human cervical cancer cells. Mol Carcinog 2004;40:201–211.
  26. Farrugia AN, Atkins GJ, To LB, Pan B, Horvath N, Kostakis P et al. Receptor activator of nuclear factor-kappaB ligand expression by human myeloma cells mediates osteoclast formation in vitro and correlates with bone destruction in vivo. Cancer Res 2003;63:5438–5445.
  27. Bhatia P, Sanders MM, Hansen MF. Expression of receptor activator of nuclear factor-kappaB is inversely correlated with metastatic phenotype in breast carcinoma. Clin Cancer Res 2005;11:162–165.
  28. Sung B, Oyajobi B, Aggarwal BB. Plumbagin inhibits osteoclastogenesis and reduces human breast cancer-induced osteolytic bone metastasis in mice through suppression of RANKL signaling. Mol Cancer Ther 2012;11:350–359.
  29. Sandur SK, Ichikawa H, Sethi G, Ahn KS, Aggarwal BB. Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) suppresses NF-kappaB activation and NF-kappaB-regulated gene products through modulation of p65 and IkappaBalpha kinase activation, leading to potentiation of apoptosis induced by cytokine and chemotherapeutic agents. J Biol Chem 2006;281:17023–17033.
  30. Kini DP, Pandey S, Shenoy BD, Singh UV, Udupa N, Umadevi P et al. Antitumor and antifertility activities of plumbagin controlled release formulations. Indian J Exp Biol 1997;35:374–379.
  31. Maruyama Y, Kuribara H, Morita M, Yuzurihara M, Weintraub ST. Identification of magnolol and honokiol as anxiolytic agents in extracts of saiboku-to, an oriental herbal medicine. J Nat Prod 1998;61:135–138.
  32. Woodbury A, Yu SP, Wei L, Garcia P. Neuro-modulating effects of honokiol: a review. Front Neurol 2013;4:130.
  33. Grivennikov SI, Karin M. Dangerous liaisons: STAT3 and NF-kappaB collaboration and crosstalk in cancer. Cytokine Growth Factor Rev 2010;21:11–19.
  34. Bollrath J, Greten FR. IKK/NF-kappaB and STAT3 pathways: central signalling hubs in inflammation-mediated tumour promotion and metastasis. EMBO Rep 2009;10:1314–1319.
  35. Lin SY, Liu JD, Chang HC, Yeh SD, Lin CH, Lee WS. Magnolol suppresses proliferation of cultured human colon and liver cancer cells by inhibiting DNA synthesis and activating apoptosis. J Cell Biochem 2002;84:532–544.
  36. Shigemura K, Arbiser JL, Sun SY, Zayzafoon M, Johnstone PA, Fujisawa M et al. Honokiol, a natural plant product, inhibits the bone metastatic growth of human prostate cancer cells. Cancer 2007;109:1279–1289.
  37. Aggarwal BB, Sung B. Pharmacological basis for the role of curcumin in chronic diseases: an age-old spice with modern targets. Trends Pharmacol Sci 2009;30:85–94.
  38. Nagpal M, Sood S. Role of curcumin in systemic and oral health: an overview. J Nat Sci Biol Med 2013;4:3–7.
  39. Singh S. From exotic spice to modern drug? Cell 2007;130:765–768.
  40. Wilken R, Veena MS, Wang MB, Srivatsan ES. Curcumin: a review of anti-cancer properties and therapeutic activity in head and neck squamous cell carcinoma. Mol Cancer 2011;10:12.
  41. Bharti AC, Takada Y, Aggarwal BB. Curcumin (diferuloylmethane) inhibits receptor activator of NF-kappa B ligand-induced NF-kappa B activation in osteoclast precursors and suppresses osteoclastogenesis. J Immunol 2004;172:5940–5947.
  42. Wright LE, Frye JB, Lukefahr AL, Timmermann BN, Mohammad KS, Guise TA et al. Curcuminoids block TGF-beta signaling in human breast cancer cells and limit osteolysis in a murine model of breast cancer bone metastasis. J Nat Prod 2013;76:316–321.
  43. Sharma RA, Steward WP, Gescher AJ. Pharmacokinetics and pharmacodynamics of curcumin. Adv Exp Med Biol 2007;595:453–470.
  44. Carroll RE, Benya RV, Turgeon DK, Vareed S, Neuman M, Rodriguez L et al. Phase IIa clinical trial of curcumin for the prevention of colorectal neoplasia. Cancer Prev Res (Phila) 2011;4:354–364.
  45. Dhillon N, Aggarwal BB, Newman RA, Wolff RA, Kunnumakkara AB, Abbruzzese JL et al. Phase II trial of curcumin in patients with advanced pancreatic cancer. Clin Cancer Res 2008;14:4491–4499.
  46. Kanai M, Yoshimura K, Asada M, Imaizumi A, Suzuki C, Matsumoto S et al. A phase I/II study of gemcitabine-based chemotherapy plus curcumin for patients with gemcitabine-resistant pancreatic cancer. Cancer Chemother Pharmacol 2011;68:157–164.
  47. Bayet-Robert M, Kwiatkowski F, Leheurteur M, Gachon F, Planchat E, Abrial C et al. Phase I dose escalation trial of docetaxel plus curcumin in patients with advanced and metastatic breast cancer. Cancer Biol Ther 2010;9:8–14.
  48. Baur JA, Sinclair DA. Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov 2006;5:493–506.
  49. Saiko P, Szakmary A, Jaeger W, Szekeres T. Resveratrol and its analogs: defense against cancer, coronary disease and neurodegenerative maladies or just a fad? Mutat Res 2008;658:68–94.
  50. Bishayee A. Cancer prevention and treatment with resveratrol: from rodent studies to clinical trials. Cancer Prev Res (Phila) 2009;2:409–418.
  51. Banerjee S, Bueso-Ramos C, Aggarwal BB. Suppression of 7,12-dimethylbenz(a)anthracene-induced mammary carcinogenesis in rats by resveratrol: role of nuclear factor-kappaB, cyclooxygenase 2, and matrix metalloprotease 9. Cancer Res 2002;62:4945–4954.
  52. Whitsett T, Carpenter M, Lamartiniere CA. Resveratrol, but not EGCG, in the diet suppresses DMBA-induced mammary cancer in rats. J Carcinog 2006;5:15.
  53. Garvin S, Ollinger K, Dabrosin C. Resveratrol induces apoptosis and inhibits angiogenesis in human breast cancer xenografts in vivo. Cancer Lett 2006;231:113–122.
  54. Harper CE, Patel BB, Wang J, Arabshahi A, Eltoum IA, Lamartiniere CA. Resveratrol suppresses prostate cancer progression in transgenic mice. Carcinogenesis 2007;28:1946–1953.
  55. Sheth S, Jajoo S, Kaur T, Mukherjea D, Sheehan K, Rybak LP et al. Resveratrol reduces prostate cancer growth and metastasis by inhibiting the Akt/MicroRNA-21 pathway. PLoS ONE 2012;7:e51655.
  56. Selcuklu SD, Donoghue MT, Spillane C. miR-21 as a key regulator of oncogenic processes. Biochem Soc Trans 2009;37:(Part 4): 918–925.
  57. Boissy P, Andersen TL, Abdallah BM, Kassem M, Plesner T, Delaisse JM. Resveratrol inhibits myeloma cell growth, prevents osteoclast formation, and promotes osteoblast differentiation. Cancer Res 2005;65:9943–9952.
  58. Kupisiewicz K, Boissy P, Abdallah BM, Hansen FD, Erben RG, Savouret JF et al. Potential of resveratrol analogues as antagonists of osteoclasts and promoters of osteoblasts. Calcif Tissue Int 2010;87:437–449.
  59. Castillo-Pichardo L, Martinez-Montemayor MM, Martinez JE, Wall KM, Cubano LA, Dharmawardhane S. Inhibition of mammary tumor growth and metastases to bone and liver by dietary grape polyphenols. Clin Exp Metastasis 2009;26:505–516.
  60. Hakimuddin F, Paliyath G, Meckling K. Selective cytotoxicity of a red grape wine flavonoid fraction against MCF-7 cells. Breast Cancer Res Treat 2004;85:65–79.
  61. Patel KR, Brown VA, Jones DJ, Britton RG, Hemingway D, Miller AS et al. Clinical pharmacology of resveratrol and its metabolites in colorectal cancer patients. Cancer Res 2010;70:7392–7399.
  62. Elkin M, Miao HQ, Nagler A, Aingorn E, Reich R, Hemo I et al. Halofuginone: a potent inhibitor of critical steps in angiogenesis progression. FASEB J 2000;14:2477–2485.
  63. Abramovitch R, Dafni H, Neeman M, Nagler A, Pines M. Inhibition of neovascularization and tumor growth, and facilitation of wound repair, by halofuginone, an inhibitor of collagen type I synthesis. Neoplasia 1999;1:321–329.
  64. Nagler A, Ohana M, Shibolet O, Shapira MY, Alper R, Vlodavsky I et al. Suppression of hepatocellular carcinoma growth in mice by the alkaloid coccidiostat halofuginone. Eur J Cancer 2004;40:1397–1403.
  65. Pinthus JH, Sheffer Y, Nagler A, Fridman E, Mor Y, Genina O et al. Inhibition of Wilms tumor xenograft progression by halofuginone is accompanied by activation of WT-1 gene expression. J Urol 2005;174:(Part 2): 1527–1531.
  66. Abramovitch R, Itzik A, Harel H, Nagler A, Vlodavsky I, Siegal T. Halofuginone inhibits angiogenesis and growth in implanted metastatic rat brain tumor model—an MRI study. Neoplasia 2004;6:480–489.
  67. Spector I, Honig H, Kawada N, Nagler A, Genin O, Pines M. Inhibition of pancreatic stellate cell activation by halofuginone prevents pancreatic xenograft tumor development. Pancreas 2010;39:1008–1015.
  68. Gavish Z, Pinthus JH, Barak V, Ramon J, Nagler A, Eshhar Z et al. Growth inhibition of prostate cancer xenografts by halofuginone. Prostate 2002;51:73–83.
  69. Juarez P, Mohammad KS, Yin JJ, Fournier PG, McKenna RC, Davis HW et al. Halofuginone inhibits the establishment and progression of melanoma bone metastases. Cancer Res 2012;72:6247–6256.
  70. De Jonge MJ, Dumez H, Verweij J, Yarkoni S, Snyder D, Lacombe D et al. Phase I and pharmacokinetic study of halofuginone, an oral quinazolinone derivative in patients with advanced solid tumours. Eur J Cancer 2006;42:1768–1774.
  71. Koon HB, Fingleton B, Lee JY, Geyer JT, Cesarman E, Parise RA et al. Phase II AIDS Malignancy Consortium trial of topical halofuginone in AIDS-related Kaposi sarcoma. J Acquir Immune Defic Syndr 2011;56:64–68.
  72. Xavier S, Piek E, Fujii M, Javelaud D, Mauviel A, Flanders KC et al. Amelioration of radiation-induced fibrosis: inhibition of transforming growth factor-beta signaling by halofuginone. J Biol Chem 2004;279:15167–15176.
  73. Roffe S, Hagai Y, Pines M, Halevy O. Halofuginone inhibits Smad3 phosphorylation via the PI3K/Akt and MAPK/ERK pathways in muscle cells: effect on myotube fusion. Exp Cell Res 2010;316:1061–1069.
  74. de Figueiredo-Pontes LL, Assis PA, Santana-Lemos BA, Jacomo RH, Lima AS, Garcia AB et al. Halofuginone has anti-proliferative effects in acute promyelocytic leukemia by modulating the transforming growth factor beta signaling pathway. PLoS ONE 2011;6:e26713.
  75. Sundrud MS, Koralov SB, Feuerer M, Calado DP, Kozhaya AE, Rhule-Smith A et al. Halofuginone inhibits TH17 cell differentiation by activating the amino acid starvation response. Science 2009;324:1334–1338.
  76. Kang Y, Siegel PM, Shu W, Drobnjak M, Kakonen SM, Cordon-Cardo C et al. A multigenic program mediating breast cancer metastasis to bone. Cancer Cell 2003;3:537–549.
Download references

Author information



Affiliations

  1. Division of Endocrinology, Department of Medicine, Indiana University-Purdue University at Indianapolis, Indianapolis, IN, USA

    • Patricia Juárez

  2. Biomedical Development Unit, Center for Scientific Research and Higher Education of Ensenada (CICESE), Ensenada, Baja California, México

    • Patricia Juárez

Conflict of Interest

The author declares no conflict of interest.
Posted by at