Artonin E: A Short Review of its Chemistry, Sources, Anti-Cancer Activities and Other Pharmacological Properties http://www.doi.org/10.26538/tjnpr/v7i6.1
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Abstract
In this short article, the chemistry, sources, anti-cancer and other medicinal properties of artonin E are reviewed for the first time. Sources of information cited on this prenylated flavonoid were from databases such as Google, Google Scholar, PubMed, Science Direct, J-Stage, Web of Science and PubChem. Artonin E or 5'-hydroxymorusin is a prenylated flavonoid from Artocarpus species (Moraceae). Its structure is that of a 3-isoprenyl 2',4',5'-trioxygenated flavone. Artonin E has been reported mostly in the root and bark of 12 Artocarpus species. The strong cytotoxic activities of artonin E are well-established and scientists from universities in Indonesia have been using artonin E as positive control when testing the cytotoxicity of compounds isolated from various plant species. The anti-cancer effects and mechanisms of artonin E have been reported in breast, lung, ovarian, colon and gastric cancer cells. Effects include apoptosis, anoikis, antiproliferation, cell cycle arrest, inhibition of migration and invasion, and overcoming tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) resistance. Mechanisms include activation of caspases, up-regulation of apoptotic proteins and down-regulation of anti-apoptotic proteins. Artonin E is endowed with a wealth of other medicinal properties. A brief account on
the medicinal properties and sources of other artonins is provided. Some prospects and further research on artonin E and other artonins are suggested.
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References
Yang X, Jiang Y, Yang J, He J, Sun J, Chen F, Zhang M, Yang B. Prenylated flavonoids, promising nutraceuticals with impressive biological activities. Trends Food Sci Technol. 2015; 44(1):93-104.
Osorio M, Carvajal M, Vergara A, Butassi E, Zacchino S, Mascayano C, Montoya M, Mejías S, Martín MC, VásquezMartínez Y. Prenylated flavonoids with potential antimicrobial activity: Synthesis, biological activity, and in silico study. Int J Mol Sci. 2021; 22(11):5472-5494.
Chen X, Mukwaya E, Wong MS, Zhang Y. A systematic review on biological activities of prenylated flavonoids. Pharm Biol. 2014; 52(5):655-660.
Jagtap UB, Bapat VA. Artocarpus: A review of its traditional uses, phytochemistry and pharmacology. J Ethnopharmacol. 2010; 129(2):142-166.
Hakim EH, Achmad SA, Juliawaty LD, Makmur L, Syah YM, Aimi N, Kitajima M, Takayama H, Ghisalberti EL. Prenylated flavonoids and related compounds of the Indonesian Artocarpus (Moraceae). J Nat Med. 2006; 60(3):161-184.
Bailly C. Anticancer mechanism of artonin E and related prenylated flavonoids from the medicinal plant Artocarpus elasticus. Asian J Nat Prod Biochem. 2021; 19(2):45-57.
Nomura T, Fukai T, Hano Y. Chemistry and biological activities of isoprenylated flavonoids from medicinal plants (Moraceous plants and Glycyrrhiza species). Stud Nat Prod Chem. 2003; 28:199-256.
Chan EWC, Wong SK, Tangah J, Chan HT. Chemistry and pharmacology of artocarpin: An isoprenyl flavone from Artocarpus species. Syst Rev Pharm. 2018; 9(1):58-63.
Chan EWC, Wong SK, Inoue T, Chan HT. Phenolic constituents from the root bark of Morus alba with emphasis on morusin and its anti-cancer properties. J Chin Pharm Sci. 2019; 28(2):75-87.
Hano Y, Yamagami Y, Kobayashi M, Isohata R, Nomura T. Artonins E and F, two new prenyflavones from the bark of Artocarpus communis Forst. Heterocycles. 1990; 31(5):877-882.
Boonphong S, Baramee A, Kittakoop P, Puangsombat P. Anti-tubercular and anti-plasmodial prenylated flavones from the roots of Artocarpus altilis. Chiang Mai J Sci, 2007; 34(3):339-344.
Wang YH, Hou AJ, Chen L, Chen DF, Sun HD, Zhao QS, Bastow KF, Nakanish Y, Wang XH, Lee KH. New isoprenylated flavones, artochamins A−E, and cytotoxic principles from Artocarpus chama. J Nat Prod. 2004; 67(5): 757-761.
Reddy GR, Ueda N, Hada T, Sackeyfio AC, Yamamoto S, Hano Y, Aida M, Nomura T. A prenylflavone, artonin E, as arachidonate 5-lipoxygenase inhibitor. Biochem Pharmacol. 1991; 41(1):115-118.
Aida M, Yamaguchi N, Hano Y, Nomura T. Artonols A, B, C, D, and E, five new isoprenylated phenols from the bark of Artocarpus communis Forst. Heterocycles. 1997; 1(45):163- 175.
Toume K, Habu T, Arai MA, Koyano T, Kowithayakorn T, Ishibashi M. Prenylated flavonoids and resveratrol derivatives isolated from Artocarpus communis with the ability to overcome TRAIL resistance. J Nat Prod. 2015; 78(1):103-110.
Kuete V, Ango PY, Fotso GW, Kapche GD, Dzoyem JP, Wouking AG, Ngadjui BT, Abegaz BM. Antimicrobial activities of the methanol extract and compounds from Artocarpus communis (Moraceae). BMC Complement Altern Med. 2011; 11(1):1-5.
Zajmi A, Mohd Hashim N, Noordin MI, Khalifa SA, Ramli F, Mohd Ali H, El-Seedi HR. Ultrastructural study on the antibacterial activity of artonin E versus streptomycin against Staphylococcus aureus strains. PLoS One. 2015; 10(6): e0128157.
Chan STS, Popplewell WL, Bokesch HR, McKee TC, Gustafson KR. Five new stilbenes from the stem bark of Artocarpus communis. Nat Prod Sci. 2018; 24(4):266-271.
Ramli F, Rahmani M, Ismail IS, Sukari MA, Rahman MA, Zajmi A, Akim AM, Hashim NM, Go R. A new bioactive secondary metabolite from Artocarpus elasticus. Nat Prod Commun. 2016; 11(8):1103-1106.
Etti IC, Abdullah RB, Hashim NM, Kadir A, Yeap SK, Sani D, Ramli F, Malami I, Waziri P. Reduction of breast tumor burden in mice by a prenylated flavonoid, artonin E. Aust Med J. 2017; 10(8):681-693.
Rahman MA, Ramli F, Karimian H, Dehghan F, Nordin N, Mohd Ali H, Mohan S, Mohd Hashim N. Artonin E induces apoptosis via mitochondrial dysregulation in SKOV-3 ovarian cancer cells. PloS One. 2016; 11(3):e0151466.
Rahman MA, Hashim NM. Apoptotic induction mechanism of artonin E in 3D ovarian cancer cell lines. Indones J Pharm.
; 33(1):147-158.
Wongpankam E, Chunhacha P, Pongrakhananon V, Sritularak B, Chanvorachote P. Artonin E mediates MCL1 down-regulation and sensitizes lung cancer cells to anoikis. Anticancer Res. 2012; 32(12):5343-5351.
Plaibua K, Pongrakhananon V, Chunhacha P, Sritularak B, Chanvorachote P. Effects of artonin E on migration and invasion capabilities of human lung cancer cells. Anticancer Res. 2013; 33(8):3079-3088.
Sritularak B, Tantituvanont A, Chanvorachote P, Meksawan K, Miyamoto T, Kohno Y, Likhitwitayawuid K. Flavonoids with free radical scavenging activity and nitric oxide inhibitory effect from the stem bark of Artocarpus gomezianus. J Med Plants Res. 2010; 4(5):387-392.
Suhartati T, Andini V, Ramadhan I, Yandri Y, Hadi S. Cytotoxicity test and antibacterial assay on the compound produced by the isolation and modification of artonin E from Artocarpus kemando Miq. Phys Sci Rev. 2022; DOI: 10.1515/psr-2021-0140.
Seo EK, Lee D, Shin YG, Chai HB, Navarro HA, Kardono L, Rahman I, Cordell GA, Farnsworth NR, Pezzuto JM, Kinghorn AD, Wani MC, Wall ME. Bioactive prenylated flavonoids from the stem bark of Artocarpus kemando. Arch Pharm Res. 2003; 26(2): 124-127.
Cao S, Butler MS, Buss AD. Flavonoids from Artocarpus lanceifolius. Nat Prod Res. 2003; 17(2):79-81.
Musthapa I, Latip J, Takayama H, Juliawaty LD, Hakim EH, Syah YM. Prenylated flavones from Artocarpus lanceifolius and their cytotoxic properties against P-388 cells. Nat Prod Commun. 2009; 4(7):927-930.
Jantan I, Mohd Yasin YH, Jamil S, Sirat H, Basar N. Effect of prenylated flavonoids and chalcones isolated from Artocarpus species on platelet aggregation in human whole blood. J Nat Med. 2010; 64(3):365-369.
Jayasinghe UL, Samarakoon TB, Kumarihamy BM, Hara N, Fujimoto Y. Four new prenylated flavonoids and xanthones from the root bark of Artocarpus nobilis. Fitoterapia. 2008; 79(1):37-41.
Liyanaararchchi GD, Perera AS, Samarasekera JK, Mahanama KR, Hemalal KD, Dlamini S, Perera HD, Alhadidi Q, Shah ZA, Tillekeratne LV. Bioactive constituents isolated from the Sri Lankan endemic plant Artocarpus nobilis and their potential to use in novel cosmeceuticals. Ind Crops Prod. 2022; 184:115076.
Hernawan, H, Suhartati T, Yandri Y, Suwandi JF. Isolation, characterization, modification, and bioactivity test of artonin E from root barks of kenangkan (Artocarpus rigida). In: International Conference on Applied Sciences Mathematics and Informatics, Bandar Lampung, Indonesia, July 2017.
Suhartati T, Yandri SH, Hadi S. The bioactivity test of artonin E from the bark of Artocarpus rigida Blume. Eur J Sci Res. 2008; 23(2):330-337.
Rattanaburi S, Sriklung K, Watanapokasin R, Mahabusarakam W. New flavonoids and xanthone from the stem bark of Artocarpus rigidus Blume and cytotoxicity. Nat Prod Res. 2021; 35(21): 4010−4017.
Suhartati T. Artonin E, a flavonoid from Artocarpus rotunda. J Mater Sci. 1999; 4:178-184.
Suhartati T, Achmad SA, Aimi N, Hakim EH, Kitajima M, Takayama H, Takeya K. Artoindonesianin L, a new prenylated flavone with cytotoxic activity from Artocarpus rotunda. Fitoterapia. 2001; 72(8):912-918.
Suhartati T, Hernawan H, Suwandi JF, Yandri Y, Hadi S. Isolation of Artonin E from the root bark of Artocarpus rigida, synthesis of artonin E acetate and evaluation of anticancer activity. Maced J Chem Chem Eng. 2018; 37(1):35-42.
Arriffin NM, Jamil S, Basar N, Khamis S, Abdullah SA, Lathiff SM. Phytochemical studies and antioxidant activities of Artocarpus scortechinii King. Rec Nat Prod. 2017; 11:299-303.
Jamil S, Sirat HM, Jantan I, Aimi N, Kitajima M. Flavonoids from Artocarpus teysmanii Miq. Mal J Sci.2005; 24(1):99-103.
Etti I, Abdullah R, Hashim NM, Kadir A, Abdul AB, Etti C, Malami I, Waziri P, How CW. Artonin E and structural analogs from Artocarpus species abrogates estrogen receptor signaling in breast cancer. Molecules. 2016; 21(7):839-856.
Etti IC, Rasedee A, Hashim NM, Abdul AB, Kadir A, Yeap SK, Waziri P, Malami I, Lim KL, Etti CJ. Artonin E induces p53-independent G1 cell cycle arrest and apoptosis through ROS-mediated mitochondrial pathway and livin suppression in MCF-7 cells. Drug Design Dev Ther. 2017; 11:865-880.
Etti I, Abdullah R, Kadir A. Apoptosis-inducing effect of artonin E in breast cancer. In: Current Understanding of Apoptosis-Programmed Cell Death, IntechOpen, pp 21-32, 2018.
Etti IC, Abdullah R, Kadir A, Hashim NM, Yeap SK, Imam MU, Ramli F, Malami I, Lam KL, Etti U, Waziri P. The molecular mechanism of the anticancer effect of artonin E in MDA-MB 231 triple negative breast cancer cells. PLoS One. 2017; 12(8): e0182357.
Tanjung M, Hakim EH, Mujahidin D, Hanafi M, Syah YM. Macagigantin, a farnesylated flavonol from Macaranga gigantea. J Asian Nat Prod Res. 2009; 11(11): 929-932.
Darmawan A, Kosela S, Kardono LB, Syah YM. Scopoletin, a coumarin derivative compound isolated from Macaranga gigantifolia Merr. J Appl Pharm Sci. 2012; 2(12):175-177.
Heliawati L, Kardinan A, Mayanti T, Tjokronegoro RA. Piceatanol: Anti-cancer compound from Gewang seed extract. J Appl Pharm Sci. 2015; 5(1):110-113.
Saputri RD, Tjahjandarie TS, Tanjung M. Meliglabrin, a new flavonol derivative from the leaves of Melicope glabra(Blume) TG Hartley. Nat Prod Sci. 2018; 24(3):155-158.
Tanjung M, Juliawaty LD, Hakim EH, Syah YM. Flavonoid and stilbene derivatives from Macaranga trichocarpa. Fitoterapia. 2018; 126:74-77.
Tanjung M, Nurmalasari I, Wilujeng AK, Saputri RD, Rachmadiarti F, Tjahjandarie TS. Acronyculatin P, a new isoprenylated acetophenone from the stem bark of Acronychia pedunculata. Nat Prod Sci. 2018; 24(4):284-287.
Tanjung M, Rachmadiarti F, Prameswari A, Ultha Wustha Agyani V, Dewi Saputri R, Srie Tjahjandarie T, Maolana Syah Y. Airlanggins AB, two new isoprenylated benzofuran- 3-ones from the stem bark of Calophyllum soulattri. Nat Prod Res. 2018; 32(13):1493-1498.
Tanjung M, Tjahjandarie TS, Saputri RD, Harsono A, Aldin MF. A new cinnamyl acid derivative from the roots of Willughbeia coriacea Wall. Nat Prod Sci. 2020; 26(1):79-82.
Hasballah K, Sarong M, Rusly R, Fitria H, Maida DR, Iqhrammullah M. Antiproliferative activity of triterpenoid and steroid compounds from ethyl acetate extract of Calotropis gigantea root bark against P388 murine leukemia cell lines. Sci Pharm. 2021; 89(2):21-32.
Paoli P, Giannoni E, Chiarugi P. Anoikis molecular pathways and its role in cancer progression. Biochim Biophys Acta -Mol Cell Res. 2013; 1833(12):3481-3498.
Sophonnithiprasert T, Mahabusarakam W, Watanapokasin R. Artonin E sensitizes TRAIL-induced apoptosis by DR5 upregulation and cFLIP downregulation in TRAIL-refractory colorectal cancer LoVo cells. J Gastrointest Oncol. 2019; 10(2):209-218.
Nimnuan-ngam S, Yangnok K, Innajak S, Watanapokasin R. Effect of artonin E on apoptosis cell death induction in colon cancer cell. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved, San Francisco, USA. September 2019.
Yangnok K, Innajak S, Sawasjirakij R, Mahabusarakam W, Watanapokasin R. Effects of artonin E on cell growth inhibition and apoptosis induction in colon cancer LoVo and HCT116 cells. Molecules. 2022; 27(7):2095-2106.
Innajak S, Tangchirakhaphan S, Nilwarangoon S, Tanjapatkul N, Mahabusarakam W, Watanapokasin R. Antiproliferation and apoptosis induction in epidermoid carcinoma A431 cells by artonin E. J Med Assoc Thai. 2017; 100(10):S54-S60.
Fukai T, Satoh K, Nomura T, Sakagami H. Anti-nephritis and radical scavenging activity of prenylflavonoids. Fitoterapia. 2003; 74(7-8):720-724.
Musthapa I, Hakim EH, Juliawaty LD, Syah YM, Achmad SA. Prenylated flavones from some Indonesian Artocarpusand their antimalarial properties. Med Plants - Int J Phytomed. 2010; 2(2):157-160.
Chaturvedi I. A molecular docking study to find natural inhibitor against FAT10 protein for curing hepatic carcinoma. J Sci. 2015; 1(2):1-9.
Sazali SN, Jalil J, Arriffin NM, Abdullah SA, Jamil S. In vitro inhibitory effects of flavonoids from the extracts of Artocarpus species on prostaglandin E2 (PGE2) production in human plasma. J Innov Pharm Biol Sci. 2017; 11:181-190.
Lee CC, Lin CN, Jow GM. Cytotoxic and apoptotic effects of prenylflavonoid artonin B in human acute lymphoblastic leukemia cells 1. Acta Pharmacologica Sinica. 2006; 27(9):1165-1174.
Namdaung U, Aroonrerk N, Suksamrarn S, Danwisetkanjana K, Saenboonrueng J, Arjchomphu W, Suksamrarn A. Bioactive constituents of the root bark of Artocarpus rigidussubsp. rigidus. Chemical and Pharmaceutical Bulletin. 2006;54(10):1433-1436.
Syah YM, Juliawaty LD, Achmad SA, Hakim EH, Ghisalberti EL. Cytotoxic prenylated flavones from Artocarpus champeden. J Nat Med. 2006; 60(4):308-312.
Bourjot M, Apel C, Martin MT, Grellier P, Guéritte F, Litaudon M. Anti-plasmodial, anti-trypanosomal, and cytotoxic activities of prenylated flavonoids isolated from the stem bark of Artocarpus styracifolius. Planta Medica. 2010;76(14):1600-1604.
Soonnarong R, Putra ID, Sriratanasak N, Sritularak B, Chanvorachote P. Artonin F induces the ubiquitinproteasomal degradation of c-Met and decreases Akt-mTOR signaling. Pharmaceuticals. 2022;15(5):633-652.
Widyawaruyanti A, Kalauni SK, Awale S, Nindatu M, Zaini NC, Syafruddin D, Asih PB, Tezuka Y, Kadota S. New prenylated flavones from Artocarpus champeden, and their antimalarial activity in vitro. Journal of Natural Medicines. 2007;61(4):410-413.
Suhartati T, Yandri Y, Suwandi JF, Yuwono SD, Qudus HI, Hadi S. In vivo antimalarial test of artocarpin and in vitroantimalarial test of artonin M isolated from Artocarpus. Revista de Chimie. 2020;71(5):400-408.
Suhartati T, Hadi S. Artonin O, a xanthone compound from root wood of Artocarpus rigida. Oriental Journal of Chemistry. 2016;32(5):2777-2784.
Ko FN, Cheng ZJ, Lin CN, Teng CM. Scavenger and antioxidant properties of prenylflavones isolated from Artocarpus heterophyllus. Free Radical Biology and Medicine. 1998;25(2):160-168.
Zhai XX, Xiao CY, Jiang W, Chen YL, Ding YQ, Ren G. Isoprenylated phenolics from roots of Artocarpus heterophyllus. Natural Product Communications. 2017;12(6):921-924.
Hano Y. Artonins A and B, two new prenylflavones from the root bark of Artocarpus heterophyllus Lamk. Heterocycles. 1989;29:1447-1453.
Hano Y, Aida M, Nomura T. Two new natural Diels-Aldertype adducts from the root bark of Artocarpus heterophyllus. Journal of Natural Products. 1990;53(2):391-395.
Aida M, Shinomiya K, Hano Y, Nomura T. Artonins J, K, and L, three new isoprenylated flavones from the root bark of Artocarpus heterophyllus Lamk. Heterocycles. 1993;36(3):575-583.
Aida M, Shinomiya K, Matsuzawa K, Hano Y, Nomura T. Artonins Q, R, S, T, and U, five new isoprenylated phenols from the bark of Artocarpus heterophyllus Lamk. Heterocycles. 1994; 2(39):847-858.
Shinomiya K, Aida M, Hano Y, Nomura T. A diels-aldertype adduct from Artocarpus heterophyllus. Phytochemistry. 1995;40(4):1317-1319.
Shinomiya K, Hano Y, Nomura T. Mechanism on one-sided Wessely-Moser rearrangement reaction. Heterocycles. 2000;53(4):877-886.
Hano Y, Yamagami Y, Kobayashi M, Isohata R, Nomura T. Artonins E and F, two new prenyflavones from the bark of Artocarpus communis Forst. Heterocycles. 1990; 31(5): 877-882.
Hano Y, Inami R, Nomura T. Components of the bark of Artocarpus rigida Bl. I, Structures of two new isoprenylated flavones, artonins G and H. Heterocycles. 1990; 31(12):2173-2179.
Hano Y, Inami R, Nomura T. Components of the bark of Artocarpus rigida BL. II: Structures of four new isoprenylated flavone derivatives artonins M, N, O, and P. Heterocycles. 1993; 35(2):1341-1350.
Hano Y, Inami R, Nomura T. A novel flavone, artonin V, from the root bark of Artocarpus altilis. Synopses. 1994; (9):348-349.