Honokiol analogs: A novel class of anticancer agents targeting cell signaling pathways and other bioactivities

Future Medicinal Chemistry

Volumn 5, Issue 7, 2013, Pages 809-829

  Kumar, Ankit ^a   Kumar Singh, Umesh ^a   Chaudhary, Anurag ^a  

^a SWAMI VIVEKANAND SUBHARTI UNIVERSITY   (India)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIINFECTIVE AGENT; ANTINEOPLASTIC AGENT; B LYMPHOCYTE RECEPTOR; BENZODIAZEPINE RECEPTOR AFFECTING AGENT; CALPAIN 2; CASPASE 10; CASPASE 2; CASPASE 8; CASPASE 9; CISPLATIN; DOCETAXEL; DOXORUBICIN; HONOKIOL; HONOKIOL DERIVATIVE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; MAMMALIAN TARGET OF RAPAMYCIN; NEUROPROTECTIVE AGENT; NEUROTROPHIC FACTOR; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PHOSPHOLIPASE D; PROTEIN TYROSINE PHOSPHATASE SHP 1; STAT3 PROTEIN; T LYMPHOCYTE RECEPTOR; TOLL LIKE RECEPTOR; UNCLASSIFIED DRUG; VASCULOTROPIN RECEPTOR;

ANTIINFLAMMATORY ACTIVITY; ANTINEOPLASTIC ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; APOPTOSIS; BLOOD BRAIN BARRIER; BREAST CANCER; CANCER GROWTH; CANCER INHIBITION; CANCER SURVIVAL; CELL PROLIFERATION; CYTOTOXICITY; DIGESTIVE SYSTEM CANCER; DNA BINDING; DRUG BIOAVAILABILITY; DRUG PROTEIN BINDING; DRUG SYNTHESIS; ENDOPLASMIC RETICULUM STRESS; ENZYME INHIBITION; GENETIC TRANSCRIPTION; HUMAN; HYDROGEN BOND; IMMUNITY; INFLAMMATION; LEWIS CARCINOMA; LIVER CANCER; LUNG CANCER; MITOCHONDRIAL PERMEABILITY; MOLECULARLY TARGETED THERAPY; NEUROPROTECTION; NONHUMAN; NUCLEAR LOCALIZATION SIGNAL; OVARY CANCER; PRIORITY JOURNAL; PROSTATE CANCER; PROTEIN PROTEIN INTERACTION; REVIEW; SIGNAL TRANSDUCTION; SKIN CANCER; STRUCTURE ACTIVITY RELATION; TRANSCRIPTION INITIATION; UBIQUITINATION;

ANTINEOPLASTIC AGENTS, PHYTOGENIC; BIPHENYL COMPOUNDS; CASPASES; HUMANS; LIGNANS; MAGNOLIA; NEOPLASMS; NF-KAPPA B; PHOSPHATIDYLINOSITOL 3-KINASES; PHOSPHOLIPASE D; SIGNAL TRANSDUCTION; STRUCTURE-ACTIVITY RELATIONSHIP; TOR SERINE-THREONINE KINASES;

EID: 84877626764     PISSN: 17568919     EISSN: 17568927     Source Type: Journal    
DOI: 10.4155/fmc.13.32     Document Type: Review

References (82)

1. 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. 61, 135-138 (1998).
2. Li H, Wang X, Hu Y. Distinct photoacidity of honokiol from magnolol. J. Fluoresc. 21, 265-273 (2011).
3. Bai X, Cerimele F, Ushio-Fukai M. Honokiol a small molecular weight natural product inhibits angiogenesis in vitro and tumor growth in vivo. J. Biol. Chem. 278, 35501-35507 (2003).
4. Fried LE, Arbiser JL. Honokiol, a multifunctional antiangiogenic and antitumor agent. Antioxid. Redox Signal. 11, 1139-1148 (2009).
5. Liou KT, Shen YC, Chen CF, Tsao CM, Tsai SK. The anti-inflammatory effect of honokiol on neutrophils: mechanisms in the inhibition of reactive oxygen species production. Eur. J. Pharmacol. 475, 19-27 (2003).
6. Tripathi S, Chan M, Chen C. An expedient synthesis of honokiol and its analogs as potential neuropreventive agents. Bioorg. Med. Chem. Lett. 22, 216-221 (2012).
7. Taferner B, Schuehly W, Huefner A, et al. Modulation of GABAA receptors by honokiol and derivatives: subtype selectivity and structure activity relationship. J. Med. Chem. 54, 5349-5361 (2011).
8. Ahn KS, Sethi G, Shishodia S, Sung B, Arbiser JL, Aggarwal BB. Honokiol potentiates apoptosis, suppresses osteoclastogenesis and inhibits invasion through modulation of nuclear factor-kappaB activation pathway. Mol. Cancer Res. 4, 621- 633 (2006).
9. Tse AK, Wan CK, Shen XL, Yang M, Fong WF. Honokiol inhibits TNF-alpha-stimulated NF-kappaB activation and NF-kappaB-regulated gene expression through suppression of IKK activation. Biochem. Pharmacol. 70, 1443-1457 (2005).
10. Leeman-Neil RJ. Prevention and treatment of head and neck cancer with natural compound inhibitors of STAT 3. Dissertation, Brandeis University, MA, USA (2002).
11. Leeman-Neil RJ, Cai Q, Joyce SC, et al. Honokiol inhibits epidermal growth factor receptor signaling and enhance the effect of epidermal growth factor receptor inhibitors. Clin. Cancer Res. 16, 2571-2579 (2010).
12. Crane C, Panner A, Pieper RO, Arbiser J, Parsa AT. Honokiol mediated inhibition of PI3k/mTOR pathway: a potential strategy to overcome immune-resistance in glioma breast and prostate carcinoma without impacting T cell function. J. Immunotherapy 32, 585-592 (2009).
13. Battle TE, Arbiser J, Frank DA. The natural product honokiol induces caspase-dependent apoptosis in B-cell chronic lymphocytic leukemia (B-CLL) cells. Blood 106, 690-697 (2005).
14. Yang SE, Hsieh MT, Tsai TH, Hsu SL. Down modulation of Bcl-XL release of cytochrome c and sequential activation of caspases during honokiol-induced apoptosis in human squamous lung cancer CH27 cells. Biochem. Pharmacol. 63, 1641-1651 (2002).
15. Teresa AL, William P, Bennett, et al. p53 Mutations, ras mutations, and p53-heat shock 70 protein complexes in human lung carcinoma cell lines. Cancer Res. 51, 4090-4096 (1991).
16. Hu J, Chen LJ, Liu L, et al. Liposomal honokiol, a potent antiangiogenesis agent, in combination with radiotherapy produces a synergistic antitumor efficacy without increasing toxicity. Exp. Mol. Med. 40, 617-628 (2008).
17. Wang T, Chen F, Chen Z, et al. Honokiol induces apoptosis through p53-independent pathway in human colorectal cell line RKO. World J. Gastroenterol. 10, 2205-2208 (2004).
18. Nagalingam A, Jack L, Arbiser, Bonner MY, Saxena NK, Sharma D. Honokiol activates AMP-activated protein kinase in breast cancer cells via an LKB1-dependent pathway and inhibits breast carcinogenesis. Breast Cancer Res. 14, R35 (2012).
19. Deng J, Quian Y, Geng L, et al. Involvement of p38 mitogen activated protein kinase pathway in honokiol-induced apoptosis in a human hepatoma cell line (hepG2). Liver Int. 28, 1458-1464 (2008).
20. Hibasami H, Achiwa Y, Katsuzaki H, et al. Honokiol induces apoptosis in human lymphoid leukemia Molt 4B cells. Int. J. Mol. Med. 2, 671-673 (1998).
21. Nagase H, Ikeda K, SakaiY. Inhibitory effect of magnolol and honokiol from Magnolia obovata on human fibrosarcoma HT-1080 invasiveness in vitro. Planta Medica. 67, 705-708 (2001).
22. Chilampalli S, Zhang X, Fahmy H, et al. Chemopreventive effect of honokiol on UVB-induced skin cancer development. Anticancer Res. 30, 777-783 (2010).
23. Liu SH, Shen CC, Yi YC, et al. Honokiol inhibit gastric tumorigenesis by activation of 15 lipoxgenase I and consequent inhibition of peroxisome proliferator activated receptor gamma and COX-2 dependent signals. Br. J. Pharmacol. 160, 1963-1972 (2010).
24. Sheu ML, Liu SH, Lan KH. Honokiol induces calpain-mediated glucose-regulated protein-94 cleavage and apoptosis in human gastric cancer cells and reduces tumor growth. PLoS ONE 2, e1096 (2007).
25. Hahm ER, Arlotti JA, Marynowski SW, Singh SV. Honokiol a constituent of oriental medicinal herb Magnolia officinalis inhibits growth of PC-3 xenografts in vivo in association with apoptosis induction. Clin. Cancer Res. 14, 1248-1257 (2008).
26. Ishitsuka K, Hideshima T, Hamasaki M. Honokiol overcomes conventional drug resistance in human multiple myeloma by induction of caspase-dependent and -independent apoptosis. Blood 106, 1794-1800 (2005).
27. Chen Y, Wub C, Liu J, Fong Y, Hsu S, Li T. Honokiol induces cell apoptosis in human chondrosarcoma cells through mitochondrial dysfunction and endoplasmic reticulum stress. Cancer Lett. 291, 20-30 (2010).
28. Sen R, Baltimore D. Inducibility of kappa immunoglobulin enhancerbinding protein Nf-kappa B by a posttranslational mechanism. Cell 47, 921-928 (1986).
29. Memet S. NF-kappaB functions in the nervous system: from development to disease. Biochem. Pharmacol. 72, 1180-1195 (2006).
30. Baldwin AS. Control of oncogenesis and cancer therapy resistance by the transcription factor NF-kappaB. J. Clin. Invest. 107, 241-246 (2001).
31. Yamamoto Y, Gaynor RB. Therapeutic potential of inhibition of the NF-kappaB pathway in the treatment of inflammation and cancer. J. Clin. Invest. 107, 135-142 (2001).
32. Baldwin AS. The NF-kappaB and I-kappaB proteins, new discoveries and insights. Annu. Rev. Immunol. 14, 649-683 (1996).
33. Karin M, Ben-Neriah Y. Phosphorylation meets ubiquitination, the control of NF- [kappa]B activity. Annu. Rev. Immunol. 18, 621-663 (2000).
34. Lu X, Farmer P, Rubin J, Nanes MS. Integration of the Nf-kappaB p65 subunit into the vitamin D receptor transcriptional complex: identification of p65 domains that inhibit 1,2,5-dihydroxyvitamin D3- stimulated transcription. J. Cell Biochem. 92, 833-848 (2004).
35. Aggarwal BB, Kunnumakkara AB, Hari KB, et al. Signal transducer and activator of transcription-3 inflammation and cancer, how intimate the relationship? Ann. NY Acad. Sci. 1171, 59-76 (2009).
36. Aggarwal BB, Sethi G, Ahn KS, et al. Targeting signal transducer and activator of transcription-3 for prevention and therapy of cancer, modern target but ancient solution. Ann. NY Acad. Sci. 1091, 151-169 (2006).
37. Rajendran P, Feng Li, Muthu K, et al. Honokiol inhibits signal transducer and activator of transcription3 signaling proliferation and survival of hepatocellular carcinoma cells via the protein tyrosine phosphatase SHP-1. J. Cell Physiol. 227, 2184-2195 (2011).
38. Ling L, Weidong H, Ying G, et al. Honokiol induces a necrotic cell death through the mitochondrial permeability transition pore. Cancer Res. 67, 4894-4903 (2007).
39. Hahm ER, Singh SV. Honokiol causes G0- G1 phase cell cycle arrest in human prostate cancer cells in association with suppression of retinoblastoma protein level/phosphorylation and inhibition of E2F1 transcriptional activity. Mol. Cancer Ther. 6, 2686-2695 (2007).
40. Li Z, Liu Y, Zhao X, et al. Honokiol a natural therapeutic candidate induces apoptosis and inhibits angiogenesis of ovarian tumor cells. Eur. J. Obstet. Gynecol. Reprod. Biol. 140, 95-102 (2008).
41. Liu SH, Wang KB, Lan KH, et al. Calpain/SHP-1 interaction by honokiol dampening peritoneal dissemination of gastric cancer in nu/nu mice. PLoS ONE 7, e43711 (2012).
42. Brian R, Anne G, Nahum S. The target of rapamycin (TOR) proteins. Proc. Natl Acad. Sci. USA 48, 7037-7044 (2000).
43. Maira S-M, Furet P, Stauffer F. Discovery of novel anticancer therapeutics targeting the PI3K/Akt/mTOR pathway. Future Med. Chem. 1, 137-150 (2009).
44. Foster DA. Phospholipase D survival signals as a therapeutic target in cancer. Curr. Signal Transduct. Ther. 1, 295-303 (2006).
45. Foster DA, Xu L. Phospholipase D in cell proliferation and cancer. Mol. Cancer Res. 1, 789-800 (2003).
46. Garcia A, Zheng Y, Zhao C, et al. Honokiol suppresses survival signals mediated by Ras dependent phospholipase D activity in human cancer cells. Clin Cancer Res. 14, 4267-4274 (2008).
47. Fantin VR, Leder P. Mitochondrion-toxic compounds for cancer therapy. Oncogene 25, 4787-4797 (2006).
48. Kroemer G. Introduction: mitochondrial control of apoptosis. Biochimie 84, 103-104 (2002).
49. Chernyak BV, Bernardi P. The mitochondrial permeability transition pore is modulated by oxidative agents through both pyridine nucleotides and glutathione at two separate sites. Eur. J. Biochem. 238, 623-630 (1996).
50. Yeretssian G, Doiron K, Shao W, et al. Gender differences in expression of the human caspase-12 long variant determines susceptibility to Listeria monocytogenes infection. Proc. Natl Acad. Sci. USA 106, 9016-9020 (2009).
51. Ikai T, Akao Y, Nakagawa Y, Ohguchi K, Sakai Y, Nozawa Y. Magnolol-induced apoptosis is mediated via the intrinsic pathway with release of AIF from mitochondria in U937 cells. Biol. Pharm. Bull. 29, 2498-2501 (2006).
52. Lodish H, Berk A, Matsudaira P, et al. Molecular Cell Biology (5th edition). WH Freeman and Co, NY, USA, 66-72 (2004).
53. Raja SM, Chen S, Yue P, et al. The natural product honokiol preferentially inhibits c-FLIP and augments death receptor induced apoptosis. Mol. Cancer Ther. 7, 2212-2223 (2008).
54. Rowinsky EK. Targeted induction of apoptosis in cancer management: the emerging role of tumor necrosis factor-related apoptosis-inducing ligand receptor activating agents. J. Clin. Oncol. 23, 9394-9407 (2005).
55. Park EJ, Min HY, Chung HJ, et al. Down-regulation of c-Src/EGFR-mediated signaling activation is involved in the honokiol-induced cell cycle arrest and apoptosis in MDA-MB-231 human breast cancer cells. Cancer Lett. 277, 133-140 (2009).
56. Singh T, Katiyar SK. Honokiol, a phytochemical from Magnolia spp., inhibits breast cancer cell migration by targeting nitric oxide and cyclooxygenase-2. Int. J. Oncol. 38, 769-776 (2011).
57. Hou W, Chen L, Yang G, et al. Synergistic antitumor effects of liposomal honokiol combined with adriamycin in breast cancer models. Phytother. Res. 22, 1125-1132 (2008).
58. Wolf I, O'Kelly J, Wakimoto N, et al. Honokiol, a natural biphenyl, inhibits in vitro and in vivo growth of breast cancer through induction of apoptosis and cell cycle arrest. Int. J. Oncol. 30, 1529-1537 (2007).
59. Luo H, Zhong Q, Chen LJ, et al. Liposomal honokiol, a promising agent for treatment of cisplatin-resistant human ovarian cancer. J. Cancer Res. Clin. Oncol. 134, 937-945 (2008).
60. Liu Y, Chen L, He X, et al. Enhancement of therapeutic effectiveness by combining liposomal honokiol with cisplatin in ovarian carcinoma. Int. J. Gynecol. Cancer 18, 652-659 (2008).
61. Shigemura K, Arbiser JL, Sun SY, et al. Honokiol, a natural plant product, inhibits the bone metastatic growth of human prostate cancer cells. Cancer 109, 1279-1289 (2007).
62. Jiang QQ, Fan LY, Yang GL, et al. Improved therapeutic effectiveness by combining liposomal honokiol with cisplatin in lung cancer model. BMC Cancer 8, 242 (2008).
63. Chen F, Wang T, Wu YF, et al. Honokiol: a potent chemotherapy candidate for human colorectal carcinoma. World J. Gastroenterol. 10, 3459-3463 (2004).
64. Arora S, Bhardwaj A, Srivastava SK, et al. Honokiol arrests cell cycle, induces apoptosis, and potentiates the cytotoxic effect of gemcitabine in human pancreatic cancer cells. PLoS ONE 6, e21573 (2011).
65. Mannal PW, Schneider J, Tangada A, McDonald D, McFadden DW. Honokiol produces anti-neoplastic effects on melanoma cells in vitro. J. Surg. Oncol. 104, 260-264 (2011).
66. Wang X, Duan X, Yang G, et al. Honokiol crosses BBB and BCSFB, and inhibits brain tumor growth in rat 9L intracerebral gliosarcoma model and human U251 xenograft glioma model. PLoS ONE 6, e18490 (2011).
67. Chen XR, Lu R, Dan HX, et al. Honokiol: a promising small molecular weight natural agent for the growth inhibition of oral squamous cell carcinoma cells. Int. J. Oral Sci. 3, 34-42 (2011).
68. Marin GH, Mansilla E. Apoptosis induced by Magnolia grandiflora extract in chlorambucil-resistant B-chronic lymphocytic leukemia cells. J. Cancer Res. Ther. 6, 463-465 (2010).
69. Fukuyama Y, Nakade K, Minoshima Y, Yokoyama R, Zhai H, Mitsumoto Y. Neurotrophic activity of honokiol on the cultures of fetal rat cortical neurons. Bioorg. Med. Chem. Lett. 12(8), 1163-1166 (2002).
70. Schuehly W, Paredes JM, Kleyer J, et al. Mechanisms of osteoclastogenesis inhibition by a novel class of biphenyl-type cannabinoid CB(2) receptor inverse agonists. Chem. Biol. 18(8), 1053-1064 (2011).
71. Alexeev M, Grosenbaugh DK, Mott DD, Fisher JL. The natural products magnolol and honokiol are positive allosteric modulators of both synaptic and extra-synaptic GABA(A) receptors. Neuropharmacology. 62(8), 2507-2514 (2012).
72. Liang M, Jinying C, Xuewei W, et al. Structural modification of honokiol a biphenyl occurring in Magnolia officinalis: the evaluation of honokiol analogs as inhibitors of angiogenesis and for their cytotoxicity and structure activity relationship. J. Med. Chem. 54, 6469-6481 (2011).
73. Lin JM, Gowda ASP, Sharma AK, Amin S. In vitro growth inhibition of human cancer cells by novel honokiol analogs. J. Bioorg. Med. Chem. 20, 3202-3211 (2012).
74. Luo Y, Xu Y, Chen L, et al. Semi-synthesis and anti-proliferative activity evaluation of novel analogs of honokiol. Bioorg. Med. Chem. Lett. 19(16), 4702-4705 (2009).
75. Amblard F, Govindarajan B, Lefkove B, et al. Synthesis, cytotoxicity, and antiviral activities of new neolignans related to honokiol and magnolol. Bioorg. Med. Chem. Lett. 17(16), 4428-4431 (2007).
76. Kong Z, Tzeng S, Liu Y. Cytotoxic neolignans: a SAR study. Bioorg. Med. Chem. Lett. 5(1), 163-166 (2005).
77. Schuehly W, Hufner A, Pferschy-Wenzig EM, et al. Design and synthesis of ten biphenyl-neolignan derivatives and their in vitro inhibitory potency against cyclooxygenase-1/2 activity and 5-lipoxygenase-mediated LTB4-formation. Bioorg. Med. Chem. 17, 4459-4465 (2009).
78. Lee B, Kwak J, Huang S, Jang J, et al. Design and synthesis of 4́-O-methylhonokiol analogs as inhibitors of cyclooxygenase-2 (COX-2) and PGF1 production. Bioorg. Med. Chem. 20(9), 2860-2868 (2012).
79. Kumar VP, Reddy Vo, Chakravarty S, Chandrasekhar S, Gree R. Synthesis and neurite growth evaluation of new analogs of honokiol, a neolignan with potent neurotrophic activity Bioorg. Med. Chem Lett. 22(3), 1439-1444 (2012).
80. Kim YS, Lee JY, Park J, Hwang W, Lee J, Park D. Synthesis and microbiological activity of honokiol derivatives as new antimicrobial agents Arch. Pharm. Res. 33(1), 61-65 (2010).
81. Yu C, Zhang Q, Zhang HY, et al. Targeting the intrinsic inflammatory pathway: honokiol exerts proapoptotic effects through STAT3 inhibition in transformed Barrett's cells. Am. J. Physiol. Gastrointest. Liver Physiol. 303, G561-G569 (2012).
82. Arora S, Singh S, Piazza GA, Contreras CM, Panyam J, Singh AP. Honokiol: a novel natural agent for cancer prevention and therapy. Curr. Mol. Med. 12, 1244-1252 (2012).