Abstract
Cancers such as breast, colon, and lung cancers are among the leading causes of death with alarming increases in the number of new diagnoses and mortality rates. The non-specific toxicity limits current standard chemotherapeutic drugs, leading to severe and long-lasting side effects. New chemotherapeutic agents are urgently needed to address this worrying issue. A potential candidate to overcome this issue is xanthone, a natural compound that has been widely investigated for its promising cytotoxic activity. Specifically, prenylated xanthones exhibit good cytotoxicity against cancer cells with structure–activity relationship studies establishing prenyl moieties as the vital substituents in cellular internalization and binding interactions with molecular targets. A combination of in vitro, in vivo, and in silico approaches showed that xanthones exhibited various actions against breast, colon, and lung cancers, ranging from apoptosis, autophagy, cell cycle arrest, and modulation of key signaling pathways such as PI3K/Akt and MAPK. Prenylated xanthones could overcome drug resistance alone or combined with chemotherapeutic agents. The latter issue further corroborates their potential as anticancer drugs. α-Mangostin (2), γ-mangostin (3), and gambogenic acid (43) are considered lead molecules for developing antitumoral agents against breast, colon, and lung cancers. Other studies showed that prenylated xanthones, such as garcinone E (8), mangostanaxanthone IV (19), cowanin (20), mangosenone F (42), and many others, have potential anticancer activity. However, more comprehensive molecular investigations are required to establish their anticancer potential. Further studies are needed to elucidate prenylated xanthones’ pharmacokinetics and toxicity profiles to continue their progression through the drug development pipeline.
Graphical abstract
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Abe Y, Tanaka N (2016) The hedgehog signaling networks in lung cancer: the mechanisms and roles in tumor progression and implications for cancer therapy. Biomed Res Int 2016:7969286. https://doi.org/10.1155/2016/7969286
Akao Y, Nakagawa Y, Iinuma M, Nozawa Y (2008) Anti-cancer effects of xanthones from pericarps of mangosteen. Int J Mol Sci 9:3355–3370
Alam S, Khan F (2014) QSAR and docking studies on xanthone derivatives for anticancer activity targeting DNA topoisomerase IIalpha. Drug Des Dev Ther 8:183–195. https://doi.org/10.2147/DDDT.S51577
Alam S, Khan F (2018) Virtual screening, docking, ADMET and system pharmacology studies on garcinia caged xanthone derivatives for anticancer activity. Sci Rep 8:15524. https://doi.org/10.1038/s41598-018-23768-7
Arai MA, Akamine R, Tsuchiya A, Yoneyama T, Koyano T, Kowithayakorn T, Ishibashi M (2018) The Notch inhibitor cowanin accelerates nicastrin degradation. Sci Rep 8:15376. https://doi.org/10.1038/s41598-018-23698-4
Atluri N, Rashmihosur, Prasad H, Palempalli UMD (2013) Antiproliferation and apoptosis induction by α-mangostin on MDA-MB-231 human breast cancer cell line. Int J Adv Pharm Res 4:92222–92229
Baell JB, Holloway GA (2010) New substructure filters for removal of Pan Assay Interference Compounds (PAINS) from screening libraries and for their exclusion in bioassays. J Med Chem 53:72719–72740
Baell JB, Nissink JWM (2018) Seven year itch: pan-assay interference compounds (PAINS) in 2017-utility and limitations. ACS Chem Biol 13:136–144. https://doi.org/10.1021/acschembio.7b00903
Banik K, Harsha C, Bordoloi D, Lalduhsaki Sailo B, Sethi G, Leong HC, Arfuso F, Mishra S, Wang L, Kumar AP, Kunnumakkara AB (2018) Therapeutic potential of gambogic acid, a caged xanthone, to target cancer. Cancer Lett 416:75–86. https://doi.org/10.1016/j.canlet.2017.12.014
Bedi P, Gupta R, Gupta R, Pramanik T, Pramanik T (2018) Synthesis and biological properties of pharmaceutically important xanthones and benzoxanthone analogs: a brief review. Asian J Pharm Clin Res 11:2. https://doi.org/10.22159/ajpcr.2018.v11i2.22426
Bukowski K, Kciuk M, Kontek R (2020) Mechanisms of multidrug resistance in cancer chemotherapy. Int J Mol Sci 21:9. https://doi.org/10.3390/ijms21093233
Cabral C, Efferth T, Pires IM, Severino P, Lemos MFL (2018) Natural products as a source for new leads in cancer research and treatment. Evid Based Complement Alternat Med 2018:8243680. https://doi.org/10.1155/2018/8243680
Chang HF, Yang LL (2012) Gamma-mangostin, a micronutrient of mangosteen fruit, induces apoptosis in human colon cancer cells. Molecules 17:78010–78021. https://doi.org/10.3390/molecules17078010
Chen J, Qiu S, Kim JT, Cho JS, Moon JH, Zhou Y, Auh JH, Lee HJ (2020) Garcinone C suppresses colon tumorigenesis through the Gli1-dependent hedgehog signaling pathway. Phytomedicine 79:153334. https://doi.org/10.1016/j.phymed.2020.153334
Chen R, Zhang H, Liu P, Wu X, Chen B (2017) Gambogenic acid synergistically potentiates bortezomib-induced apoptosis in multiple myeloma. J Cancer 8:5839–5851. https://doi.org/10.7150/jca.17657
Chi X-Q, Zi C-T, Li H-M, Yang L, Lv Y-F, Li J-Y, Hou B, Ren F-C, Hu J-M, Zhou J (2018) Design, synthesis and structure–activity relationships of mangostin analogs as cytotoxic agents. RSC Adv 8:7241377–7241388. https://doi.org/10.1039/c8ra08409b
Chitchumroonchokchai C, Thomas-Ahner JM, Li J, Riedl KM, Nontakham J, Suksumrarn S, Clinton SK, Kinghorn AD, Failla ML (2013) Anti-tumorigenicity of dietary α-mangostin in an HT-29 colon cell xenograft model and the tissue distribution of xanthones and their phase II metabolites. Mol Nutr Food Res 57:2203–2211. https://doi.org/10.1002/mnfr.201200539
Chowchaikong N, Nilwarangkoon S, Laphookhieo S, Tanunyutthawongse C, Watanapokasin R (2018) p38 inhibitor inhibits the apoptosis of cowanin-treated human colorectal adenocarcinoma cells. Int J Oncol 52:62031–62040. https://doi.org/10.3892/ijo.2018.4353
Cragg GM, Pezzuto JM (2016) Natural products as a vital source for the discovery of cancer chemotherapeutic and chemopreventive agents. Med Princ Pract 25(Suppl 2):41–59. https://doi.org/10.1159/000443404
Ding YY, Luan JJ, Fan Y, Olatunji OJ, Song J, Zuo J (2020) α-Mangostin reduced the viability of A594 cells in vitro by provoking ROS production through downregulation of NAMPT/NAD. Cell Stress Chaperones 25:1163–1172. https://doi.org/10.1007/s12192-019-01063-2
Ekins S, Mestres J, Testa B (2007) In silico pharmacology for drug discovery: applications to targets and beyond. Br J Pharmacol 152:121–137. https://doi.org/10.1038/sj.bjp.0707306
El-Agamy DS, Mohamed GA, Ahmed N, Elkablawy MA, Elfaky MA, Elsaed WM, Mohamed SGA, Ibrahim SRM (2020) Protective anti-inflammatory activity of tovophyllin A against acute lung injury and its potential cytotoxicity to epithelial lung and breast carcinomas. Inflammopharmacology 28(1):153–163. https://doi.org/10.1007/s10787-019-00609-1
Fazry S, Noordin MAM, Sanusi S, Noor MM, Aizat WM, Lazim AM, Dyari HRE, Jamar NH, Remali J, Othman BA, Law D, Sidik NM, Cheah YH, Lim YC (2018) Cytotoxicity and toxicity evaluation of xanthone crude extract on hypoxic human hepatocellular carcinoma and zebrafish (Danio rerio) embryos. Toxics 6:4. https://doi.org/10.3390/toxics6040060
Feng C, Huang SX, Gao XM, Xu HX, Luo KQ (2014) Characterization of proapoptotic compounds from the bark of Garcinia oblongifolia. J Nat Prod 77:51111–51116. https://doi.org/10.1021/np4007316
Gertsch J (2009) How scientific is the science in ethnopharmacology? Historical perspectives and epistemological problems. J Ethnopharmacol 122:2177–2183. https://doi.org/10.1016/j.jep.2009.01.010
Gunter NV, Teh SS, Lim YM, Mah SH (2020) Natural xanthones and skin inflammatory diseases: multitargeting mechanisms of action and potential application. Front Pharmacol 11:594202. https://doi.org/10.3389/fphar.2020.594202
Haerani SN, Raksat A, Pudhom K (2021) Two new xanthones from the root of Thai Calophyllum inophyllum and their toxicity against colon and liver cancer cells. J Nat Med 75:670–674. https://doi.org/10.1007/s11418-021-01492-3
Haider T, Pandey V, Banjare N, Gupta PN, Soni V (2020) Drug resistance in cancer: mechanisms and tackling strategies. Pharmacol Rep 72:51125–51151. https://doi.org/10.1007/s43440-020-00138-7
Hatami E, Jaggi M, Chauhan SC, Yallapu MM (2020) Gambogic acid: a shining natural compound to nanomedicine for cancer therapeutics. Biochim Biophys Acta Rev Cancer 1874:1188381. https://doi.org/10.1016/j.bbcan.2020.188381
He Y, Ding J, Lin Y, Li J, Shi Y, Wang J, Zhu Y, Wang K, Hu X (2015) Gambogenic acid alters chemosensitivity of breast cancer cells to Adriamycin. BMC Complement Altern Med 15:181. https://doi.org/10.1186/s12906-015-0710-8
Ibrahim MY, Hashim NM, Mohan S, Abdulla MA, Kamalidehghan B, Ghaderian M, Dehghan F, Ali LZ, Arbab IA, Yahayu M, Lian GE, Ahmadipour F, Ali HM (2014) α-Mangostin from Cratoxylum arborescens demonstrates apoptogenesis in MCF-7 with regulation of NF-κB and Hsp70 protein modulation in vitro, and tumor reduction in vivo. Drug Des Dev Ther 8:1629–1647. https://doi.org/10.2147/DDDT.S66105
Ibrahim SRM, Abdallah HM, El-Halawany AM, Nafady AM, Mohamed GA (2018a) Mangostanaxanthone VIII, a new xanthone from Garcinia mangostana and its cytotoxic activity. Nat Prod Res 33:2258–2265. https://doi.org/10.1080/14786419.2018.1446012
Ibrahim SRM, Abdallah HM, El-Halawany AM, Radwan MF, Shehata IA, Al-Harshany EM, Zayed MF, Mohamed GA (2018b) Garcixanthones B and C, new xanthones from the pericarps of Garcinia mangostana and their cytotoxic activity. Phytochem Lett 25:12–16. https://doi.org/10.1016/j.phytol.2018.03.009
Ibrahim SRM, Mohamed GA, Elfaky MA, Haidari A, Zayed RA, El-Kholy MF, Khedr AIM (2018c) Garcixanthone A, a new cytotoxic xanthone from the pericarps of Garcinia mangostana. J Asian Nat Prod Res 21:3291–3297. https://doi.org/10.1080/10286020.2017.1423058
Jeon SM, Lee DS, Jeong GS (2016) Cudraticusxanthone A isolated from the roots of Cudrania tricuspidata inhibits metastasis and induces apoptosis in breast cancer cells. J Ethnopharmacol 194:57–62. https://doi.org/10.1016/j.jep.2016.08.042
Kaewpiboon C, Boonnak N, Kaowinn S, Chung YH (2018) Formoxanthone C, isolated from Cratoxylum formosum ssp. pruniflorum, reverses anticancer drug resistance by inducing both apoptosis and autophagy in human A549 lung cancer cells. Bioorg Med Chem Lett 28:4820–4825. https://doi.org/10.1016/j.bmcl.2017.07.066
Karunakaran T, Ee GCL, Tee KH, Ismail IS, Zamakshshari NH, Peter WM (2016) Cytotoxic prenylated xanthone and coumarin derivatives from Malaysian Mesua beccariana. Phytochem Lett 17:131–134. https://doi.org/10.1016/j.phytol.2016.07.026
Klein-Junior LC, Campos A, Niero R, Correa R, Vander Heyden Y, Filho VC (2020) Xanthones and cancer: from natural sources to mechanisms of action. Chem Biodivers 17:2e1900499. https://doi.org/10.1002/cbdv.201900499
Kosem N, Ichikawa K, Utsumi H, Moongkarndi P (2012) In vivo toxicity and antitumor activity of mangosteen extract. J Nat Med 67:2255–2263. https://doi.org/10.1007/s11418-012-0673-8
Krishnamachary B, Subramaniam D, Dandawate P, Ponnurangam S, Srinivasan P, Ramamoorthy P, Umar S, Thomas SM, Dhar A, Septer S, Weir SJ, Attard T, Anant S (2019) Targeting transcription factor TCF4 by γ-mangostin, a natural xanthone. Oncotarget 10:545576–545591. https://doi.org/10.18632/oncotarget.27159
Kritsanawong S, Innajak S, Imoto M, Watanapokasin R (2016) Antiproliferative and apoptosis induction of α-mangostin in T47D breast cancer cells. Int J Oncol 48:52155–52165. https://doi.org/10.3892/ijo.2016.3399
Kuete V, Mbaveng AT, Nono EC, Simo CC, Zeino M, Nkengfack AE, Efferth T (2016) Cytotoxicity of seven naturally occurring phenolic compounds towards multi-factorial drug-resistant cancer cells. Phytomedicine 23:8856–8863. https://doi.org/10.1016/j.phymed.2016.04.007
Kuete V, Sandjo LP, Ouete JL, Fouotsa H, Wiench B, Efferth T (2014) Cytotoxicity and modes of action of three naturally occurring xanthones (8-hydroxycudraxanthone G, morusignin I and cudraxanthone I) against sensitive and multidrug-resistant cancer cell lines. Phytomedicine 21:3315–3322. https://doi.org/10.1016/j.phymed.2013.08.018
Kurose H, Shibata MA, Iinuma M, Otsuki Y (2012) Alterations in cell cycle and induction of apoptotic cell death in breast cancer cells treated with α-mangostin extracted from mangosteen pericarp. J Biomed Biotechnol 2012:672428. https://doi.org/10.1155/2012/672428
Lee KW, Zamakshshari NH, Ee GCL, Mah SH, Mohd Nor SM (2018) Isolation and structural modifications of ananixanthone from Calophyllum teysmannii and their cytotoxic activities. Nat Prod Res 32:182147–182151. https://doi.org/10.1080/14786419.2017.1367781
Li G, Thomas S, Johnson JJ (2013) Polyphenols from the mangosteen (Garcinia mangostana) fruit for breast and prostate cancer. Front Pharmacol 4:80. https://doi.org/10.3389/fphar.2013.00080
Li P, Tian WX, Ma XF (2014) Alpha-mangostin inhibits intracellular fatty acid synthase and induces apoptosis in breast cancer cells. Mol Cancer 13:138. https://doi.org/10.1186/1476-4598-13-138
Liang Y, Luo D, Gao X, Wu H (2018) Inhibitory effects of garcinone E on fatty acid synthase. RSC Adv 8:158112–158117. https://doi.org/10.1039/c7ra13246h
Liu Y, Chen Y, Lin L, Li H (2020) Gambogic acid as a candidate for cancer therapy: a review. Int J Nanomed 15:10385–10399. https://doi.org/10.2147/IJN.S277645
Ma Y, Yu W, Shrivastava A, Srivastava RK, Shankar S (2019) Inhibition of pancreatic cancer stem cell characteristics by α-Mangostin: molecular mechanisms involving Sonic hedgehog and Nanog. J Cell Mol Med 23:42719–42730. https://doi.org/10.1111/jcmm.14178
Mah SH, Ee GC, Teh SS, Rahmani M, Lim YM, Go R (2012) Phylattrin, a new cytotoxic xanthone from Calophyllum soulattri. Molecules 17:78303–78311. https://doi.org/10.3390/molecules17078303
Mah SH, Ee GC, Teh SS, Sukari MA (2014) Calophyllum inophyllum and Calophyllum soulattri source of anti-proliferative xanthones and their structure–activity relationships. Nat Prod Res 29:198–101. https://doi.org/10.1080/14786419.2014.959949
Mariano LN, Vendramini-Costa DB, Ruiz AL, de Carvalho JE, Correa R, Filho C, Delle Monache V, Niero R (2016) In vitro antiproliferative activity of uncommon xanthones from branches of Garcinia achachairu. Pharm Biol 54:91697–91704. https://doi.org/10.3109/13880209.2015.1123279
McGlynn LM, Zino S, MacDonald AI, Curle J, Reilly JE, Mohammed ZM, McMillan DC, Mallon E, Payne AP, Edwards J, Shiels PG (2014) SIRT2: tumour suppressor or tumour promoter in operable breast cancer? Eur J Cancer 50:2290–2301. https://doi.org/10.1016/j.ejca.2013.10.005
Mei W, Dong C, Hui C, Bin L, Fenggen Y, Jingjing S, Cheng P, Meiling S, Yawen H, Xiaoshan W, Guanghui W, Zhiwu C, Qinglin L (2014) Gambogenic acid kills lung cancer cells through aberrant autophagy. PLoS ONE 9:1e83604. https://doi.org/10.1371/journal.pone.0083604
Miladiyah I, Jumina J, Haryana SM, Mustofa M (2018) Biological activity, quantitative structure–activity relationship analysis, and molecular docking of xanthone derivatives as anticancer drugs. Drug Des Dev Ther 12:149–158. https://doi.org/10.2147/DDDT.S149973
Mittermair E, Krenn L, Marian B (2019) Prenylated xanthones from Metaxya rostrata suppress FoxM1 and induce active cell death by distinct mechanisms. Phytomedicine 60:152912. https://doi.org/10.1016/j.phymed.2019.152912
Mittermair E, Schueffl H, Heffeter P, Krenn L, Marian B (2020) Destabilization of FoxM1 and inhibition of topoisomerase I contribute to cytotoxicity of prenylated xanthones isolated from Metaxya rostrata. Planta Med 86:151073–151079. https://doi.org/10.1055/a-1097-8722
Mizushina Y, Kuriyama I, Nakahara T, Kawashima Y, Yoshida H (2013) Inhibitory effects of α-mangostin on mammalian DNA polymerase, topoisomerase, and human cancer cell proliferation. Food Chem Toxicol 59:793–800. https://doi.org/10.1016/j.fct.2013.06.027
Mohamed GA, Al-Abd AM, El-Halawany AM, Abdallah HM, Ibrahim SRM (2017) New xanthones and cytotoxic constituents from Garcinia mangostana fruit hulls against human hepatocellular, breast, and colorectal cancer cell lines. J Ethnopharmacol 198:302–312. https://doi.org/10.1016/j.jep.2017.01.030
Muchtaridi M, Dermawan D, Yusuf M (2018) Molecular docking, 3D structure-based pharmacophore modeling, and ADME prediction of alpha mangostin and its derivatives against estrogen receptor alpha. J Young Pharm 10:3252–3259. https://doi.org/10.5530/jyp.2018.10.58
Nakanishi T, Ross DD (2012) Breast cancer resistance protein (BCRP/ABCG2): its role in multidrug resistance and regulation of its gene expression. Chin J Cancer 31:273–299
Nauman MC, Tocmo R, Vemu B, Veenstra JP, Johnson JJ (2020) Inhibition of CDK2/CyclinE1 by xanthones from the mangosteen (Garcinia mangostana): a structure–activity relationship study. Nat Prod Res. https://doi.org/10.1080/14786419.2020.1777413
Ng IMJ, Chua CLL (2019) The potential of xanthones as a therapeutic option in macrophage-associated inflammatory diseases. Pharmacogn Rev 13:2528–2533. https://doi.org/10.4103/phrev.phrev_25_18
Nguyen TTH, Qu Z, Nguyen VT, Nguyen TT, Le TTA, Chen S, Ninh ST (2022) Natural prenylated xanthones as potential inhibitors of PI3k/Akt/mTOR pathway in triple negative breast cancer cells. Planta Med. https://doi.org/10.1055/a-1728-5166
Nie S, Huang Y, Shi M, Qian X, Li H, Peng C, Kong B, Zou X, Shen S (2018) Protective role of ABCG2 against oxidative stress in colorectal cancer and its potential underlying mechanism. Oncol Rep 40:42137–42146. https://doi.org/10.3892/or.2018.6594
Phan TKT, Shahbazzadeh F, Pham TTH, Kihara T (2018) Alpha-mangostin inhibits the migration and invasion of A549 lung cancer cells. PeerJ 6:e5027. https://doi.org/10.7717/peerj.5027
Pinto MMM, Palmeira A, Fernandes C, Resende D, Sousa E, Cidade H, Tiritan ME, Correia-da-Silva M, Cravo S (2021) From natural products to new synthetic small molecules: a journey through the world of xanthones. Molecules 26:2. https://doi.org/10.3390/molecules26020431
Prakash O, Kumar A, Kumar P, Ajeet A (2013) Anticancer potential of plants and natural products: a review. Am J Pharmacol Sci 1:6104–6115. https://doi.org/10.12691/ajps-1-6-1
Resh MD (2013) Covalent lipid modifications of proteins. Curr Biol 23:10R431–R435. https://doi.org/10.1016/j.cub.2013.04.024
Riobo-Del Galdo NA, Lara Montero A, Wertheimer EV (2019) Role of hedgehog signaling in breast cancer: pathogenesis and therapeutics. Cells 8:4. https://doi.org/10.3390/cells8040375
Saeidnia S, Manayi A, Abdollahi M (2013) The pros and cons of the in-silico pharmaco-toxicology in drug discovery and development. Int J Pharmacol 9:3176–3181. https://doi.org/10.3923/ijp.2013.176.181
Sangsuwon C, Jiratchariyakul W (2015) Antiproliferative effect of lung cancer cell lines and antioxidant of macluraxanthone from Garcinia Speciosa Wall. Procedia Soc Behav Sci 197:1422–1427. https://doi.org/10.1016/j.sbspro.2015.07.089
Saraswathy SUP, Lalitha LCP, Rahim S, Gopinath C, Haleema S, SarojiniAmma S, Aboul-Enein HY (2022) A review on synthetic and pharmacological potential of compounds isolated from Garcinia mangostana Linn. Phytomed Plus 2:2. https://doi.org/10.1016/j.phyplu.2022.100253
Scolamiero G, Pazzini C, Bonafe F, Guarnieri C, Muscari C (2018) Effects of α-mangostin on viability, growth and cohesion of multicellular spheroids derived from human breast cancer cell lines. Int J Med Sci 15:123–130. https://doi.org/10.7150/ijms.22002
See I, Ee GCL, Jong VYM, Teh SS, Acuna CLC, Mah SH (2020) Cytotoxic activity of phytochemicals from Garcinia mangostana L. and G. benthamiana (Planch. & Triana) Pipoly against breast cancer cells. Nat Prod Res. https://doi.org/10.1080/14786419.2020.1836629
Seo KH, Ryu HW, Park MJ, Park KH, Kim JH, Lee MJ, Kang HJ, Kim SL, Lee JH, Seo WD, Mangosenone F (2015) A furanoxanthone from Garciana mangostana, induces reactive oxygen species-mediated apoptosis in lung cancer cells and decreases xenograft tumor growth. Phytother Res 29:111753–111760. https://doi.org/10.1002/ptr.5428
Shahbazi S, Kuanar A (2016) Semiemperical investigation of the postmenopausal breast cancer treatment potential of xanthone derivatives. Nat Prod Chem Res 04:02. https://doi.org/10.4172/2329-6836.1000206
Shahbazi S, Kuanar A, Gade DR, Kar D, Shrivastava A, Kunala P, Mahto MK (2016) Semiemperical investigation of the postmenopausal breast cancer treatment potential of xanthone derivatives. Nat Prod Chem Res 04:02. https://doi.org/10.4172/2329-6836.1000206
Shibata MA, Iinuma M, Morimoto J, Kurose H, Akamatsu K, Okuno Y, Akao Y, Otsuki Y (2011) α-Mangostin extracted from the pericarp of the mangosteen (Garcinia mangostana Linn) reduces tumor growth and lymph node metastasis in an immunocompetent xenograft model of metastatic mammary cancer carrying a p53 mutation. BMC Med 9:69. https://doi.org/10.1186/1741-7015-9-69
Soares JX, Loureiro DRP, Dias AL, Reis S, Pinto MMM, Afonso CMM (2022) Bioactive marine xanthones: a review. Mar Drugs 20:1. https://doi.org/10.3390/md20010058
Sukandar ER, Kaennakam S, Rassamee K, Ersam T, Siripong P, Tip-Pyang S, Tetrandraxanthones A-I (2019) Prenylated and geranylated xanthones from the stem bark of Garcinia tetrandra. J Nat Prod 82:51312–51318. https://doi.org/10.1021/acs.jnatprod.9b00046
Sun Y, Li D, Jia C, Xue C, Bai J, Li Z, Hua H (2016) Three new xanthones from the leaves of Garcinia lancilimba. J Nat Med 70:2173–2178. https://doi.org/10.1007/s11418-015-0950-4
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F (2021) Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Cancer J Clin 71:3209–3249. https://doi.org/10.3322/caac.21660
Tang Y, Hou J, Li G, Song Z, Li X, Yang C, Liu W, Hu Y, Xu Y (2014) ABCG2 regulates the pattern of self-renewing divisions in cisplatin-resistant non-small cell lung cancer cell lines. Oncol Rep 32:52168–52174
Tang YX, Fu WW, Wu R, Tan HS, Shen ZW, Xu HX (2016) Bioassay-guided isolation of prenylated xanthone derivatives from the leaves of Garcinia oligantha. J Nat Prod 79:71752–71761. https://doi.org/10.1021/acs.jnatprod.6b00137
Teh SS, Ee GC, Mah SH, Lim YM, Ahmad Z (2013) Cytotoxicity and structure–activity relationships of xanthone derivatives from Mesua beccariana, Mesua ferrea and Mesua congestiflora towards nine human cancer cell lines. Molecules 18:21985–21994. https://doi.org/10.3390/molecules18021985
Usui T, Sakurai M, Umata K, Elbadawy M, Ohama T, Yamawaki H, Hazama S, Takenouchi H, Nakajima M, Tsunedomi R, Suzuki N, Nagano H, Sato K, Kaneda M, Sasaki K (2018) Hedgehog signals mediate anti-cancer drug resistance in three-dimensional primary colorectal cancer organoid culture. Int J Mol Sci 19:4. https://doi.org/10.3390/ijms19041098
Vemu B, Nauman MC, Veenstra JP, Johnson JJ (2019) Structure activity relationship of xanthones for inhibition of cyclin dependent kinase 4 from mangosteen (Garcinia mangostana L.). Int J Nutr 4:238–245
Wahyuni FS, Shaari K, Stanslas J, Lajis NH, Hamidi D (2016) Cytotoxic properties and complete nuclear magnetic resonance assignment of isolated xanthones from the root of Garcinia cowa Roxb. Pharmacognosy Magazine 12:4552–4556. https://doi.org/10.4103/0973-1296.176115
Won YS, Lee JH, Kwon SJ, Kim JY, Park KH, Lee MK, Seo KI (2014) α-Mangostin-induced apoptosis is mediated by estrogen receptor α in human breast cancer cells. Food Chem Toxicol 66:158–165. https://doi.org/10.1016/j.fct.2014.01.040
Wu CP, Hsiao SH, Murakami M, Lu YJ, Li YQ, Huang YH, Hung TH, Ambudkar SV, Wu YS (2017) Alpha-mangostin reverses multidrug resistance by attenuating the function of the multidrug resistance-linked ABCG2 transporter. Mol Pharm 14:82805–82814. https://doi.org/10.1021/acs.molpharmaceut.7b00334
Wu J, Dai J, Zhang Y, Wang J, Huang L, Ding H, Li T, Zhang Y, Mao J, Yu S (2019) Synthesis of novel xanthone analogues and their growth inhibitory activity against human lung cancer A549 cells. Drug Des Dev Ther 13:4239–4246. https://doi.org/10.2147/DDDT.S217827
Xia Y, Liu X, Zou C, Feng S, Guo H, Yang Y, Lei Y, Zhang J, Lu Y (2018) Garcinone C exerts antitumor activity by modulating the expression of ATR/Stat3/4EBP1 in nasopharyngeal carcinoma cells. Oncol Rep 39:31485–31493. https://doi.org/10.3892/or.2018.6218
Xu L, Meng X, Xu N, Fu W, Tan H, Zhang L, Zhou Q, Qian J, Tu S, Li X, Lao Y, Xu H (2018) Gambogenic acid inhibits fibroblast growth factor receptor signaling pathway in erlotinib-resistant non-small-cell lung cancer and suppresses patient-derived xenograft growth. Cell Death Dis 9(3):262. https://doi.org/10.1038/s41419-018-0314-6
Xu Z, Huang L, Chen XH, Zhu XF, Qian XJ, Feng GK, Lan WJ, Li HJ (2014) Cytotoxic prenylated xanthones from the pericarps of Garcinia mangostana. Molecules 19(2):1820–1827. https://doi.org/10.3390/molecules19021820
Yeong KY, Khaw KY, Takahashi Y, Itoh Y, Murugaiyah V, Suzuki T (2020) Discovery of gamma-mangostin from Garcinia mangostana as a potent and selective natural SIRT2 inhibitor. Bioorg Chem 94:103403. https://doi.org/10.1016/j.bioorg.2019.103403
Yeh YH, Chen JH, Chen CL (2020) The effect of Ananixanthone in TGF- ß1 signaling. The FASEB Journal 34(S1):1. https://doi.org/10.1096/fasebj.2020.34.s1.05366
Yu XJ, Han QB, Wen ZS, Ma L, Gao J, Zhou GB (2012) Gambogenic acid induces G1 arrest via GSK3β-dependent cyclin D1 degradation and triggers autophagy in lung cancer cells. Cancer Lett 322:2185–2194. https://doi.org/10.1016/j.canlet.2012.03.004
Zamakshshari NH, Ee GCL, Ismail IS, Ibrahim Z, Mah SH (2019) Cytotoxic xanthones isolated from Calophyllum depressinervosum and Calophyllum buxifolium with antioxidant and cytotoxic activities. Food Chem Toxicol 133:110800. https://doi.org/10.1016/j.fct.2019.110800
Zhang BJ, Fu WW, Wu R, Yang JL, Yao CY, Yan BX, Tan HS, Zheng CW, Song ZJ, Xu HX (2019) Cytotoxic prenylated xanthones from the leaves of Garcinia bracteata. Planta Med 85:6444–6452. https://doi.org/10.1055/a-0828-9831
Zhang C, Yu G, Shen Y (2017a) The naturally occurring xanthone α-mangostin induces ROS-mediated cytotoxicity in non-small scale lung cancer cells. Saudi J Biol Sci 25:61090–61095. https://doi.org/10.1016/j.sjbs.2017.03.005
Zhang KJ, Gu QL, Yang K, Ming XJ, Wang JX (2017b) Anticarcinogenic effects of alpha-mangostin: a review. Planta Med 83:3–04188. https://doi.org/10.1055/s-0042-119651
Funding
This work was supported by the Fundamental Research Grant Scheme (FRGS/1/2019/STG01/TAYLOR/02/1) from the Ministry of Higher Education (MOHE).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest or competing financial interest.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Gunter, N.V., Teh, S.S., Jantan, I. et al. The mechanisms of action of prenylated xanthones against breast, colon, and lung cancers, and their potential application against drug resistance. Phytochem Rev 22, 467–503 (2023). https://doi.org/10.1007/s11101-022-09846-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11101-022-09846-9