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Anticancer Activities and Mechanism of Action of Nagilactones, a Group of Terpenoid Lactones Isolated from Podocarpus Species |
Christian Bailly |
OncoWitan, 59290 Lille(Wasquehal), France |
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Abstract Nagilactones are tetracyclic natural products isolated from various Podocarpus species. These lactone-based compounds display a range of pharmacological effects, including antifungal, anti-atherosclerosis, anti-inflammatory and anticancer activities reviewed here. The most active derivatives, such as nagilactones C, E and F, exhibit potent anticancer activities against different cancer cell lines and tumor models. A comprehensive analysis of their mechanism of action indicates that their anticancer activity mainly derives from three complementary action:(i) a drug-induced inhibition of cell proliferation coupled with a cell cycle perturbation and induction of apoptosis, (ii) a blockade of the epithelial to mesenchymal cell transition contributing to an inhibition of cancer cell migration and invasion and (iii) a capacity to modulate the PD-L1 immune checkpoint. Different molecular effectors have been implicated in the antitumor activity, chiefly the AP-1 pathway blocked upon activation of the JNK/c-Jun axis. Nag-C is a potent inhibitor of protein synthesis binding to eukaryotic ribosomes and inhibition of different protein kinases, such as RIOK2 and JAK2, has been postulated with Nag-E. The literature survey on nagilactones highlights the therapeutic potential of these little-known terpenoids. The mechanistic analysis also provides useful information for structurally related compounds (podolactones, oidiolactones, inumakilactones) isolated from Podocarpus plants.
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Keywords
Cancer
Natural products
Mechanism of action
Molecular target
Terpenoids
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Corresponding Authors:
Christian Bailly
E-mail: christian.bailly@oncowitan.com
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Issue Date: 24 December 2020
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1. Y. Hayashi, S. Takahashi, H. Ona, T. Sakan, Tetrahedron Lett. 17, 2071-2076 (1968) 2. Y. Hayashi, J. Yokoi, Y. Watanabe, T. Sakan, Chem Lett. 1(9), 759-762 (1972) 3. D.P. Little, P. Knopf, C. Schulz, PLoS ONE 8, e81008 (2013) 4. G.B. Russell, P.G. Fenemore, P. Singh, Aust. J. Biol. Sci. 25, 1025-1029 (1972) 5. B.P. Ying, I. Kubo, Phytochemistry 34, 1107-1110 (1993) 6. K. Shrestha, A.H. Banskota, S. Kodata, S.P. Shrivastava, G. Strobel, M.B. Gewali, Phytomedicine 8, 489-491 (2001) 7. Y.J. Kuo, S.Y. Hwang, M.D. Wu, C.C. Liao, Y.H. Liang, Y.H. Kuo, H.O. Ho, Chem. Pharm. Bull. (Tokyo) 56, 585-588 (2008) 8. H.S. Abdillahi, G.I. Stafford, J.F. Finnie, J. Van Staden, S. Afr. J. Bot. 76, 1-24 (2010) 9. L.C. Zhang, X.D. Wu, J. He, Y. Li, R.P. Zhang, Q.S. Zhao, Phytochem. Lett. 6, 364-367 (2013) 10. E.M. Addo, H.B. Chai, A. Hymete, M.Y. Yeshak, C. Slebodnick, D.G. Kingston, L.H. Rakotondraibe, J. Nat. Prod. 78, 827-835 (2015) 11. Y.D. Zheng, X.C. Guan, D. Li, A.Q. Wang, C.Q. Ke, C.P. Tang, L.G. Lin, Y. Ye, Z.L. Wang, S. Yao, Molecules 21, 1282 (2016) 12. H. Zhao, H. Li, G. Huang, Y. Chen, Nat. Prod. Res. 31, 844-848 (2017) 13. L.J. Xuan, Y.M. Xu, S.D. Fang, Phytochemistry 39, 1143-1145 (1995) 14. L. Faiella, A. Temraz, N. De Tommasi, A. Braca, Phytochemistry 76, 172-177 (2012) 15. Y.D. Zheng, G. Bai, C. Tang, C.Q. Ke, S. Yao, L.J. Tong, F. Feng, Y. Li, J. Ding, H. Xie, Y. Ye, Fitoterapia 125, 174-183 (2018) 16. Y. Hayashi, T. Matsumoto, J. Org. Chem. 47, 3421-3428 (1982) 17. A.F. Barrero, Q. Del Moral, M. Marherrador, Stud. Nat. Prod. Chem. 28, 453-516 (2003) 18. I. Kubo, B.P. Ying, Phytochemistry 1991(30), 3476-3477 (1991) 19. Y. Ohmae, K. Shibata, T. Yamakura, J. Chem. Ecol. 22, 477-489 (1996) 20. I. Kubo, T. Matsumoto, J.A. Klocke, J. Chem. Ecol. 10, 547-559 (1984) 21. H. Yasui, J. Chem. Ecol. 27, 1345-1353 (2001) 22. P. Singh, P.G. Fenemore, G.B. Russell, Aust. J. Biol. Sci. 26, 911-915 (1973) 23. P. Singh, G.B. Russell, Y. Hayashi, R.T. Gallagher, S. Fredericksen, Entomol. Exp. Appl. 25, 121-127 (1979) 24. I. Kubo, H. Muroi, M. Himejima, J. Nat. Prod. 56, 220-226 (1993) 25. Y. Hayashi, T. Sakan, Gan 66, 587-588 (1975) 26. Y.Y. Qi, J. Su, Z.J. Zhang, L.W. Li, M. Fan, Y. Zhu, X.D. Wu, Q.S. Zhao, Chem. Biodivers. 15, e1800043 (2018) 27. S.Y. Huang, L.Y. Fan, Y.C. Shen, C.C. Liao, L.C. Hsu, Y.W. Hsu, T.S. Wu, P.C. Hsiao, C.C. Shen, M.J. Don, Y.H. Kuo, J. Asian Nat. Prod. Res. 11, 410-416 (2009) 28. Z.L. Feng, L.L. Zhang, Y.D. Zheng, Q.Y. Liu, J.X. Liu, L. Feng, L. Huang, Q.W. Zhang, J.J. Lu, L.G. Lin, J. Nat. Prod. 80, 2110-2117 (2017) 29. K. Sato, Y. Inaba, H.S. Park, T. Akiyama, T. Koyama, H. Fukaya, Y. Aoyagi, K. Takeya, Chem. Pharm. Bull. (Tokyo) 57, 668-679 (2009) 30. L.L. Zhang, Z.L. Feng, M.X. Su, X.M. Jiang, X. Chen, Y. Wang, A. Li, L.G. Lin, J.J. Lu, Eur. J. Pharmacol. 830, 17-25 (2018) 31. H. Shan, S. Yao, Y. Ye, Q. Yu, Acta Pharmacol. Sin. 40, 1578-1586 (2019) 32. P.A. Benatrehina, W.L. Chen, A.A. Czarnecki, S. Kurina, H.B. Chai, D.D. Lantvit, T.N. Ninh, X. Zhang, D.D. Soejarto, J.E. Burdette, A.D. Kinghorn, L.H. Rakotondraibe, Nat. Prod. Bioprospect. 9, 157-163 (2019) 33. L.L. Zhang, J. Guo, X.M. Jiang, X.P. Chen, Y.T. Wang, A. Li, L.G. Lin, H. Li, J.J. Lu, Acta Pharmacol. Sin. 41, 698-705 (2020) 34. K. Hayashi, Y. Yamaguchi, A. Ogita, T. Tanaka, I. Kubo, K.I. Fujita, Fitoterapia 128, 112-117 (2018) 35. K. Fujita, M. Tatsumi, A. Ogita, I. Kubo, T. Tanaka, FEBS J. 281, 1304-1313 (2014) 36. K.I. Fujita, T. Ishikura, Y. Jono, Y. Yamaguchi, A. Ogita, I. Kubo, T. Tanaka, Biochim. Biophys. Acta Gen. Subj. 1861, 477-484 (2017) 37. Z.L. Feng, T. Zhang, J.X. Liu, X.P. Chen, L.S. Gan, Y. Ye, L.G. Lin, J. Nat. Med. 72, 882-889 (2018) 38. S.J. Chen, W.C. Huang, T.T. Yang, J.H. Lu, L.T. Chuang, Food Chem. Toxicol. 50, 3687-3695 (2012) 39. Y. Gui, S. Yao, H. Yan, L. Hu, C. Yu, F. Gao, C. Xi, H. Li, Y. Ye, Y. Wang, Cardiovasc. Res. 112, 502-514 (2016) 40. A. Li, X. Xiao, Z.L. Feng, X. Chen, L.J. Liu, L.G. Lin, J.J. Lu, L.L. Zhang, Toxicol. Appl. Pharmacol. 389, 114882 (2020) 41. Y. Sun, X. Jiang, Y. Lu, J. Zhu, L. Yu, B. Ma, Q. Zhang, Chem. Biol. Interact. 296, 57-64 (2018) 42. C.S. Cheng, J.X. Chen, J. Tang, Y.W. Geng, L. Zheng, L.L. Lv, L.Y. Chen, Z. Chen, Cancer Manag. Res. 12, 641-651 (2020) 43. L.L. Zhang, X.M. Jiang, M.Y. Huang, Z.L. Feng, X. Chen, Y. Wang, H. Li, A. Li, L.G. Lin, J.J. Lu, Phytomedicine 52, 32-39 (2019) 44. K.P. Devkota, R. Ratnayake, N.H. Colburn, J.A. Wilson, C.J. Henrich, J.B. McMahon, J.A. Beutler, J. Nat. Prod. 74, 374-377 (2011) 45. S. Trop-Steinberg, Y. Azar, Am. J. Med. Sci. 353, 474-483 (2017) 46. V. Atsaves, V. Leventaki, G.Z. Rassidakis, Cancers (Basel) 11, 1037 (2019) 47. Y.C. Chen, M.Y. Huang, L.L. Zhang, Z.L. Feng, X.M. Jiang, L.W. Yuan, R.Y. Huang, B. Liu, H. Yu, Y.T. Wang, X.P. Chen, L.G. Lin, J.J. Lu, Chin. J. Nat. Med. 18, 517-525 (2020) 48. H.R. Zhou, K. He, J. Landgraf, X. Pan, J.J. Pestka, Toxins (Basel) 6, 3406-3425 (2014) 49. J. Chan, S.N. Khan, I. Harvey, W. Merrick, J. Pelletier, RNA 10, 528-543 (2004) 50. N. Garreau de Loubresse, I. Prokhorova, W. Holtkamp, M.V. Rodnina, G. Yusupova, M. Yusupov, Nature 513, 517-522 (2014) 51. J. Wang, T. Varin, M. Vieth, J.M. Elkins, Open Biol. 9, 190037 (2019) 52. F. Maurice, N. Pérébaskine, S. Thore, S. Fribourg, RNA Biol. 16, 1633-1642 (2019) 53. Y. Song, C. Li, L. Jin, J. Xing, Z. Sha, T. Zhang, D. Ji, R. Yu, S. Gao, J. Cell. Mol. Med. 24, 4494-4509 (2020) 54. B.E. Campbell, P.R. Boag, A. Hofmann, C. Cantacessi, C.K. Wang, P. Taylor, M. Hu, Z.U. Sindhu, A. Loukas, P.W. Sternberg, R.B. Gasser, Biotechnol. Adv. 29, 338-350 (2011) 55. H. Zhou, T. Zhou, B. Zhang, W. Lei, W. Yuan, J. Shan, Y. Zhang, N. Gupta, M. Hu, Int. J. Parasitol 50, 595-602 (2020) 56. H. Cai, X. Qin, C. Yang, J. Cell. Biochem. 118, 3381-3390 (2017) 57. N.H. Thoennissen, G.B. Iwanski, N.B. Doan, R. Okamoto, P. Lin, S. Abbassi, J.H. Song, D. Yin, M. Toh, W.D. Xie, J.W. Said, H.P. Koeffler, Cancer Res. 69, 5876-5884 (2009) 58. Q. Zheng, Y. Liu, W. Liu, F. Ma, Y. Zhou, M. Chen, J. Chang, Y. Wang, G. Yang, G. He, Mol. Med. Rep. 10, 89-94 (2014) 59. S. Liu, S. Chen, J. Zeng, Mol. Med. Rep. 17, 699-704 (2018) 60. Global Biodiversity Information Facility (GBIF). https://www.gbif.org/fr/species/2687779. Accessed 9 Aug 2020 61. Y. Yang, J. Yong, C. Lu, Biomed. Res. Rev. 2, 1-5 (2018) 62. Y. Hayashi, T. Matsumoto, T. Hyono, N. Nishikawa, M. Uemura, M. Nishizawa, M. Togami, T. Sakan, Tetrahedron Lett. 1979(35), 3311-3314 (1979) 63. S.D. Burke, M.E. Kort, S.M.S. Strickland, H.M. Organ, L.A. Silks Ⅲ, Tetrahedron Lett. 35, 1503-1506 (1994) 64. S. Hanessian, N. Boyer, G.J. Reddy, B. Deschênes-Simard, Org. Lett. 11, 4640-4643 (2009) 65. E. Lautié, O. Russo, P. Ducrot, J.A. Boutin, Front. Pharmacol. 11, 397 (2020) 66. N. Ye, Y. Ding, C. Wild, Q. Shen, J. Zhou, J. Med. Chem. 57, 6930-6948 (2014) 67. E.F. Gilman, D.G. Watson, University of Florida, IFAS extension #ENH656. https://edis.ifas.ufl.edu/st497. Accessed 7 Aug 2020. 68. Y. Hayashi, T. Matsumoto, M. Uemura, M. Koreeda, Org. Magn. Res. 14, 86-91 (1980) 69. Y. Hayashi, T. Matsumoto, M. Nishizawa, M. Togami, T. Hyono, N. Nishikawa, M. Uemura, T. Sakan, J. Org. Chem. 47, 3428-3433 (1982) 70. J.A. Hembree, C.J. Chang, J.M. McLaughlin, J.M. Cassady, D.J. Watts, E. Wenkert, S.F. Fonseca, J.D.P. Campello, Phytochemistry 18, 1691-1694 (1979) |
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