A Mini-Review on the Structural Characteristics and Anticancer Activity of Nagilactones

Article ID: e070623217729 Pages: 7

  • * (Excluding Mailing and Handling)

Abstract

Natural products provide abundant resources for the development of new drugs. Podocarpus nagi is an arbor of Podocarpus L'Hér. ex Persoon. Its fruits, leaves, and roots exhibit a broad spectrum of pharmacological activities (such as antitumor, plant growth regulation, termite killing, and insect larval toxicity), which have been used in Yao folk for a long history. Nagilactone is one of the key components discovered in Podocarpus nagi, which has a variety of structures and a broad spectrum of antitumor activities. In this mini-review, the structures and spectral characteristics, together with the antitumor activities and the structure-activity relationships of nagilactones, are summarized by searching the database in order to provide detailed references for researchers to elucidate and modify their structures.

Graphical Abstract

[1]
Abdillahi HS, Verschaeve L, Finnie JF, Van Staden J. Mutagenicity, antimutagenicity and cytotoxicity evaluation of South African Podocarpus species. J Ethnopharmacol 2012; 139(3): 728-38.
[http://dx.doi.org/10.1016/j.jep.2011.11.044] [PMID: 22155396]
[2]
Hayashi Y, Matsumoto T, Tashiro T. Antitumor activity of norditerpenoid dilactones in Podocarpus plants: Structure-activity relationship on in vitro cytotoxicity against Yoshida sarcoma. Gann 1979; 70(3): 365-9.
[PMID: 572795]
[3]
Yang Y, Yong JP, Olagoke ZO. First isolation and confirmation of sterol based on β-sitosterol skeleton from the leaves of Podocarpusnagi Planted in Fujian, preliminary in vitro anticancer activity and the crystal structure. Chin J Struc Chem 2021; 40(5): 653-8.
[4]
Yang Y, Yong J, Lu C. Chemical and biological progress of Podocarpus nagi. Biomed Res Rev 2018; 2(3): 1-5.
[http://dx.doi.org/10.15761/BRR.1000118]
[5]
Yong JP, Lu CZ, Yang Y. Extraction method and application of sterides from Podocarpus nagi leaves. China Patent CN 112300239 B, 2020.
[6]
Yong JP, Yang Y, Tian DN. Study on the large-scale preparation, chemical constituents of Podocarpus Nagi kernel oil and in vitro antioxidant and anticancer activities. Acad J Med Plant 2022; 10(3): 22-39.
[7]
Xiao Y, Yong J, Yang Y, Lu C. The ethyl acetate extraction obtained from podocarpus nagi kernel meal with anticancer activity. Biomed Pharmacol J 2021; 14(1): 363-6.
[http://dx.doi.org/10.13005/bpj/2134]
[8]
Yong JP, Lu CZ, Xiao YC. Extraction method and application of ethyl acetate from Podocarpus nagi kernel meal. China Patent 202011199776.2, 2020.
[9]
Barrero AF, Quilez Del Moral JF, Mar Herrador M. Podolactones: A group of biologically active norditerpenoids. Stud Nat Prod Chem 2003; 28: 453-516.
[http://dx.doi.org/10.1016/S1572-5995(03)80147-3]
[10]
Hayashi Y, Matsumoto T, Uemura M, Koreeda M. Carbon-13 NMR studies of the biologically active nor-diterpenoid dilactones fromPodocarpus plants. Org Magn Reson 1980; 14(2): 86-91.
[http://dx.doi.org/10.1002/mrc.1270140203]
[11]
Xu YM, Fang SD. Chemical constituents of Podocarpus fleuryi Hickel. Zhiwuxue Tongbao 1990; 32(4): 302-6.
[12]
Xu YM, Fang SD. Structure of a new diflavone in Podocarpus fleuryi Hickel. Zhiwuxue Tongbao 1991; 33(2): 162-3.
[13]
Xu YM, Fang SD. Chemical constituents of Podocarpus fleuryi Hickel (II). Zhiwuxue Tongbao 1991; 33(5): 406-8.
[14]
Xu YM, Fang SD. Studied on chemical constituents of Podocarpaceae Endl. I. Antitumor constituents of Podocarpus nagi. Aata Chim Sinica 1989; 47: 1086-108.
[15]
Xu YM, Fang SD. Two new diterpene dilactones from Podocarpus nagi. Zhiwuxue Tongbao 1993; 35(2): 133-7.
[16]
Bloor SJ, Molloy BPJ. Cytotoxic norditerpene lactones from Ileostylus micranthus. J Nat Prod 1991; 54(5): 1326-30.
[http://dx.doi.org/10.1021/np50077a015] [PMID: 1800635]
[17]
Banerjee K, Resat H. Constitutive activation of STAT3 in breast cancer cells: A review. Int J Cancer 2016; 138(11): 2570-8.
[http://dx.doi.org/10.1002/ijc.29923] [PMID: 26559373]
[18]
Fathi N, Rashidi G, Khodadadi A, Shahi S, Sharifi S. STAT3 and apoptosis challenges in cancer. Int J Biol Macromol 2018; 117: 993-1001.
[http://dx.doi.org/10.1016/j.ijbiomac.2018.05.121] [PMID: 29782972]
[19]
Jing N, Tweardy DJ. Targeting Stat3 in cancer therapy. Anticancer Drugs 2005; 16(6): 601-7.
[http://dx.doi.org/10.1097/00001813-200507000-00002] [PMID: 15930886]
[20]
Shan H, Yao S, Ye Y, Yu Q. 3-Deoxy-2β,16-dihydroxyna-gilactone E, a natural compound from Podocarpus nagi, preferentially inhibits JAK2/STAT3 signaling by allosterically interacting with the regulatory domain of JAK2 and induces apoptosis of cancer cells. Acta Pharmacol Sin 2019; 40(12): 1578-86.
[http://dx.doi.org/10.1038/s41401-019-0254-4] [PMID: 31201357]
[21]
Benatrehina PA, Chen WL, Czarnecki AA, et al. Bioactivity-guided isolation of totarane-derived diterpenes from podocarpus neriifolius and Structure Revision of 3-Deoxy-2α-hydroxynagilactone E. Nat Prod Bioprospect 2019; 9(2): 157-63.
[http://dx.doi.org/10.1007/s13659-019-0198-x] [PMID: 30783922]
[22]
Feng ZL, Zhang LL, Zheng YD, et al. Norditerpenoids and Dinorditerpenoids from the Seeds of Podocarpus nagi as Cytotoxic Agents and Autophagy Inducers. J Nat Prod 2017; 80(7): 2110-7.
[http://dx.doi.org/10.1021/acs.jnatprod.7b00347] [PMID: 28719204]
[23]
Reck M, Popat S, Reinmuth N, De Ruysscher D, Kerr KM, Peters S. Metastatic non-small-cell lung cancer (NSCLC): ESMO clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2014; 25(3) (Suppl. 3): iii27-39.
[http://dx.doi.org/10.1093/annonc/mdu199] [PMID: 25115305]
[24]
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin 2020; 70(1): 7-30.
[http://dx.doi.org/10.3322/caac.21590] [PMID: 31912902]
[25]
Zheng R, Zhang S, Zeng H, et al. Cancer incidence and mortality in China, 2016. Journal of the National Cancer Center 2022; 2(1): 1-9.
[http://dx.doi.org/10.1016/j.jncc.2022.02.002]
[26]
Zhang LL, Feng ZL, Su MX, et al. Downregulation of Cyclin B1 mediates nagilactone E-induced G2 phase cell cycle arrest in non-small cell lung cancer cells. Eur J Pharmacol 2018; 830: 17-25.
[http://dx.doi.org/10.1016/j.ejphar.2018.04.020] [PMID: 29680228]
[27]
Lamouille S, Xu J, Derynck R. Molecular mechanisms of epithelial–mesenchymal transition. Nat Rev Mol Cell Biol 2014; 15(3): 178-96.
[http://dx.doi.org/10.1038/nrm3758] [PMID: 24556840]
[28]
Zhang LL, Jiang XM, Huang MY, et al. Nagilactone E suppresses TGF-β1-induced epithelial–mesenchymal transition, migration and invasion in non-small cell lung cancer cells. Phytomedicine 2019; 52: 32-9.
[http://dx.doi.org/10.1016/j.phymed.2018.09.222] [PMID: 30599910]
[29]
Zou W. Immunosuppressive networks in the tumour environment and their therapeutic relevance. Nat Rev Cancer 2005; 5(4): 263-74.
[http://dx.doi.org/10.1038/nrc1586] [PMID: 15776005]
[30]
Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 2012; 12(4): 252-64.
[http://dx.doi.org/10.1038/nrc3239] [PMID: 22437870]
[31]
Chen YC, Huang MY, Zhang LL, et al. Nagilactone E increases PD-L1 expression through activation of c-Jun in lung cancer cells. Chin J Nat Med 2020; 18(7): 517-25.
[http://dx.doi.org/10.1016/S1875-5364(20)30062-5] [PMID: 32616192]
[32]
Ren Y, Kinghorn AD. Development of potential antitumor agents from the scaffolds of plant-derived Terpenoid Lactones. J Med Chem 2020; 63(24): 15410-48.
[http://dx.doi.org/10.1021/acs.jmedchem.0c01449] [PMID: 33289552]