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Recent Patents on Anti-Cancer Drug Discovery

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ISSN (Print): 1574-8928
ISSN (Online): 2212-3970

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Mini-Review Article

Anti-cancer Research on Arnebiae radix-derived Naphthoquinone in Recent Five Years

Author(s): Lian Zhu, Kailin Li, Mingjuan Liu, Kexin Liu, Shengjun Ma* and Wei Cai*

Volume 17, Issue 3, 2022

Published on: 21 February, 2022

Page: [218 - 230] Pages: 13

DOI: 10.2174/1574892816666211209164745

Price: $65

Abstract

Background: In recent years, many naphthoquinone compounds with anticancer activity have been identified in Arnebiae Radix, and some of them have the potential to be developed into anticancer drugs.

Objective: This article aimed to provide a comprehensive overview of the anticancer effects of naphthoquinone compounds through a detailed review of literature and Chinese patents, and discuss their potential to be developed as anticancer drugs for clinical application.

Methods: Research papers were collected through the databases of PubMed, Cnki and SciDirect using keyword searches “naphthoquinone compounds” and “anticancer”. The keywords of “shikonin” and “shikonin derivatives” were also used in PubMed, Cnki and SciDirect databases to collect research articles. The Chinese patents were collected using the Cnki patent database.

Results: Naphthoquinone compounds have been found to possess anti-cancer activity, and their modes of action are associated with inducing apoptosis, inhibiting cancer cell proliferation, promoting autophagy in cancer cells, anti-cancer angiogenesis and inhibition of cell adhesion, invasion and metastasis, inhibiting glycolysis and inhibiting DNA topoisomerase activity.

Conclusion: Most of the naphthoquinone compounds show effective anti-cancer activity in vitro. The structure modification of naphthoquinone aims to develop anti-cancer drugs with high efficacy and low toxicity.

Keywords: Arnebiae radix, anti-cancer, naphthoquinone compounds, shikonin derivatives, apoptosis, autophagy.

« Previous Next »
[1]
Hanahan D, Weinberg RA. Hallmarks of cancer: The next generation. Cell 2011; 144(5): 646-74.
[http://dx.doi.org/10.1016/j.cell.2011.02.013] [PMID: 21376230]
[2]
Kushlinskiĭ NE, Nemtsova MV. Molecular biological characteristics of cancer. Vestn Ross Akad Med Nauk 2014; (1-2): 5-15.
[http://dx.doi.org/10.15690/vramn.v69i1-2.934] [PMID: 25055553]
[3]
Newman DJ, Cragg GM. Natural products as sources of new drugs over the last 25 years. J Nat Prod 2007; 70(3): 461-77.
[http://dx.doi.org/10.1021/np068054v] [PMID: 17309302]
[4]
Harvey AL, Edrada-Ebel R, Quinn RJ. The re-emergence of natural products for drug discovery in the genomics era. Nat Rev Drug Discov 2015; 14(2): 111-29.
[http://dx.doi.org/10.1038/nrd4510] [PMID: 25614221]
[5]
Zhan ZL, Hu J, Liu T, Kang LP, Nan TG, Guo LP. Advances in studies on chemical compositions and pharmacological activities of Arnebiae radix. Zhongguo Zhongyao Zazhi 2015; 40(21): 4127-35.
[PMID: 27071244]
[6]
Zhang J, et al. Herbal textual analysis of medicinal plant arnebia. J Anhui Agr Sci 2019; 47(23): 199-202.
[http://dx.doi.org/10.3969/j.issn.0517-6611.2019.23.058]
[7]
Establishment of polymerase chain reaction method in Chinese Pharmacopoeia (2020 edition). Zhongguo Zhong Yao Za Zhi 2020; 45(19): 4537-44.
[http://dx.doi.org/10.19540/j.cnki.cjcmm.20200603.609] [PMID: 33164416]
[8]
Wada N, Kawano Y, Fujiwara S, et al. Shikonin, dually functions as a proteasome inhibitor and a necroptosis inducer in multiple myeloma cells. Int J Oncol 2015; 46(3): 963-72.
[http://dx.doi.org/10.3892/ijo.2014.2804] [PMID: 25530098]
[9]
Zhu XF. Effect of shikonin on interleukin-22-mediated HaCaT biological behaviour and its mechanism. Yangzhou University 2013. Available from: www.dissertationtopic.net/doc/215778.
[10]
Wang F, Yao X, Zhang Y, Tang J. Synthesis, biological function and evaluation of Shikonin in cancer therapy. Fitoterapia 2019; 134: 329-39.
[http://dx.doi.org/10.1016/j.fitote.2019.03.005] [PMID: 30858045]
[11]
Zhou W, Jiang HdaG, Peng Y, Li SS. Comparative study on enantiomeric excess of main akannin/shikonin derivatives isolated from the roots of three endemic Boraginaceae plants in China. Biomed Chromatogr 2011; 25(10): 1067-75.
[http://dx.doi.org/10.1002/bmc.1570] [PMID: 21308700]
[12]
Sun YT, Li TT, Han Y, et al. Isolation and extraction of isovalerylshikonin in Arnebia guttata Bunge. Jilin Normal University Journal 2019; 40(2): 86-8.
[http://dx.doi.org/10.16862/j.cnki.issn1674-3873.2019.02.016]
[13]
Mao Y, Cai XC, et al. Simultaneous determination of six naphthoquinones in Xinjiang Arnebiae radix. Chin Tradit Herbal Drugs 2019; 50(17): 4170-5.
[http://dx.doi.org/10.7501/j.issn.0253-2670.2019.17.024]
[14]
Dwivedi P. ROS mediated apoptotic pathways in primary effusion lymphoma: Comment on induction of apoptosis by Shikonin through ROS-mediated intrinsic and extrinsic pathways in primary effusion lymphoma. Transl Oncol 2021; 14(7): 101061.
[http://dx.doi.org/10.1016/j.tranon.2021.101061] [PMID: 33857745]
[15]
Ko H, Kim SJ, Shim SH, Chang H, Ha CH. Shikonin induces the apoptotic cell death via regulation of p53 and Nrf2 in AGS human stomach carcinoma cells. Biomol Ther (Seoul) 2016; 24(5): 501-9.
[http://dx.doi.org/10.4062/biomolther.2016.008] [PMID: 27257011]
[16]
Liu C, Yin L, Chen J, Chen J. The apoptotic effect of shikonin on human papillary thyroid carcinoma cells through mitochondrial pathway. Tumour Biol 2014; 35(3): 1791-8.
[http://dx.doi.org/10.1007/s13277-013-1238-5] [PMID: 24081676]
[17]
Yang XH, Lv BY, Mao QL, et al. Research progress on the biological activity of tea pigments. Jiangxi Nongye Daxue Xuebao 2012; 24(1): 102-5.
[http://dx.doi.org/10.19386/j.cnki.jxnyxb.2012.01.031]
[18]
Huang G, Zhao HR, Zhou W, et al. 6-Substituted 1,4-naphthoquinone oxime derivatives (I): Synthesis and evaluation of their cytotoxic activity. Monatsh Chem 2017; 148(6): 1011-23.
[http://dx.doi.org/10.1007/s00706-016-1899-z]
[19]
Zhang Y, Xu WT, Wang H, et al. Recent advances in antitumor activity of naphthaquinones. Anim Husb Feed Sci 2017; 38(11): 100-2.
[http://dx.doi.org/10.16003/j.cnki.issn1672-5190.2017.11.028]
[20]
Li SS, Cui JH. Racemic shikonin oxime amino acid ester derivative preparation method and application. CN110128291A, 2019.
[21]
Li SS, Zhang QJ, Cui JH. Shikonin oxime derivative containing nitrogen side chain preparation method and medical application. CN110041180A, 2019.
[22]
Li SS, Huang G, Meng QQ, Zhao HR. Sulfur-containing shikonin oxime derivative and application. CN109384697, 2019.
[23]
Li SS, Cui JH. Racemic shikonin oxime amino acid ester derivative preparation method and application. CN110128291B, 2020.
[24]
Li SS, Zhang QJ, Cui JH. Shikonin oxime derivative containing nitrogen side chain preparation method and medical application. CN110041180B, 2020.
[25]
Wang R, Zhang X, Song H, Zhou S, Li S. Synthesis and evaluation of novel alkannin and shikonin oxime derivatives as potent antitumor agents. Bioorg Med Chem Lett 2014; 24(17): 4304-7.
[http://dx.doi.org/10.1016/j.bmcl.2014.07.012] [PMID: 25127868]
[26]
Huang G, Zhao HR, Meng QQ, et al. Synthesis and biological evaluation of sulfur-containing shikonin oxime derivatives as potential antineoplastic agents. Eur J Med Chem 2018; 143: 166-81.
[http://dx.doi.org/10.1016/j.ejmech.2017.11.031] [PMID: 29174813]
[27]
Yang YH, Lin HY, Feng L. A class of shikonin lipothioether twin drug molecule and its synthesis method and application. CN111892575, 2020.
[28]
Li SS, Huang G, Meng QQ, Zhao HR. Sulfur-containing shikonin oxime derivative and its application. CN109384697, 2020.
[29]
Sun WX, Jiang P, Zhao SS, et al. Shikonin carboxylate derivatives containing cinnamic acid skeleton synthesis method and application. CN111960995, 2020.
[30]
Jiang P, Sun WW, Liu MM, Zhao SY, Guo YJ, et al. Novel shikonin phenylacetate derivatives containing benzenesulfonamide structural unit synthesis method and application. CN112010791, 2020.
[31]
Yang YH, Wang XM, Lin HY. Shikonin lipoic acid ester derivatives synthesis method and application. CN107304197, 2021.
[32]
Yang YH, Wang XM, Wang ZZ, Qiu HY, Luo YL. Shikonin carboxylate derivatives synthesis method and application. CN105153060, 2021.
[33]
Papageorgiou VP, Assimopoulou AN, Couladouros EA, Hepworth D, Nicolaou KC. The chemistry and biology of alkannin, shikonin, and related naphthazarin natural products. Angew Chem Int Ed Engl 1999; 38(3): 270-301.
[http://dx.doi.org/10.1002/(SICI)1521-3773(19990201)38:3<270::AID-ANIE270>3.0.CO;2-0] [PMID: 29711637]
[34]
Ahn BZ, Baik KU, Kweon GR, Lim K, Hwang BD. Acylshikonin analogues: Synthesis and inhibition of DNA topoisomerase-I. J Med Chem 1995; 38(6): 1044-7.
[http://dx.doi.org/10.1021/jm00006a025] [PMID: 7699697]
[35]
Yang YH, Chu SJ, Hu C, et al. Synthesis and biological activity evaluation of shikonin benzoyl acrylate carboxylate derivatives. CN108863798, 2018.
[36]
Durchschein C, Hufner A, Rinner B, et al. Synthesis of novel shikonin derivatives and pharmacological effects of cyclopropylacetylshikonin on melanoma cells. Molecules 2018; 23(11): 2820-93.
[http://dx.doi.org/10.3390/molecules23112820] [PMID: 30380765]
[37]
Lin HY, Han HW, Bai LF, et al. Design, synthesis and biological evaluation of shikonin thio-glycoside derivatives: New anti-tubulin agents. RSC Advances 2014; 4(91): 49796-805.
[http://dx.doi.org/10.1039/C4RA08810G]
[38]
Kerr JF, Wyllie AH, Currie AR. Apoptosis: A basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 1972; 26(4): 239-57.
[http://dx.doi.org/10.1038/bjc.1972.33] [PMID: 4561027]
[39]
Yang Q, Li S, Fu Z, et al. Shikonin promotes adriamycin‑induced apoptosis by upregulating caspase-3 and caspase-8 in osteosarcoma. Mol Med Rep 2017; 16(2): 1347-52.
[http://dx.doi.org/10.3892/mmr.2017.6729] [PMID: 28627658]
[40]
Sun H, Zhang AJ, Wang XJ. Preparation method and application of Arnebiae radix extract. CN103494860, 2014.
[41]
Xu J, Koizumi K, Liu M, et al. Shikonin induces an anti‑tumor effect on murine mammary cancer via p38-dependent apoptosis. Oncol Rep 2019; 41(3): 2020-6.
[http://dx.doi.org/10.3892/or.2019.6966] [PMID: 30664166]
[42]
Hu X, Fang JP. Application of shikonin in preparing medicine for treating cancer diseases. CN1579378, 2005.
[43]
Hong M, Li J, Li S, M Almutairi M. Acetylshikonin sensitizes hepatocellular carcinoma cells to apoptosis through ROS-Mediated caspase activation. Cells 2019; 8(11): 1-19.
[http://dx.doi.org/10.3390/cells8111466] [PMID: 31752383]
[44]
Wang HB, Ma XQ, Ma XQ, et al. β, β-Dimethylacrylshikonin induces mitochondria-dependent apoptosis of human lung adenocarcinoma cells in vitro via p38 pathway activation. Acta Pharmacol Sin 2015; 36(1): 131-8.
[http://dx.doi.org/10.1038/aps.2014.108] [PMID: 25434989]
[45]
Gong K, Li W. Shikonin, a Chinese plant-derived naphthoquinone, induces apoptosis in hepatocellular carcinoma cells through reactive oxygen species: A potential new treatment for hepatocellular carcinoma. Free Radic Biol Med 2011; 51(12): 2259-71.
[http://dx.doi.org/10.1016/j.freeradbiomed.2011.09.018] [PMID: 22011623]
[46]
Wu YY, Wan LH, Zheng XW, et al. Inhibitory effects of β,β-dimethylacrylshikonin on hepatocellular carcinoma in vitro and in vivo. Phytother Res 2012; 26(5): 764-71.
[http://dx.doi.org/10.1002/ptr.3623] [PMID: 22109831]
[47]
Tang X, Zhang C, Wei J, Fang Y, Zhao R, Yu J. Apoptosis is induced by shikonin through the mitochondrial signaling pathway. Mol Med Rep 2016; 13(4): 3668-74.
[http://dx.doi.org/10.3892/mmr.2016.4967] [PMID: 26935754]
[48]
Liang W, Cui J, Zhang K, et al. Shikonin induces ROS-based mitochondria-mediated apoptosis in colon cancer. Oncotarget 2017; 8(65): 109094-106.
[http://dx.doi.org/10.18632/oncotarget.22618] [PMID: 29312593]
[49]
Hou Y, Xu J, Liu X, Xia X, Li N, Bi X. Shikonin induces apoptosis in the human gastric cancer cells HGC-27 through mitochondria-mediated pathway. Pharmacogn Mag 2015; 11(42): 250-6.
[http://dx.doi.org/10.4103/0973-1296.153074] [PMID: 25829762]
[50]
Yeh YC, Liu TJ, Lai HC. Shikonin induces apoptosis, necrosis, and premature senescence of human A549 lung cancer cells through upregulation of p53 expression. Evid Based Complement Alternat Med 2015; 2015: 620383.
[http://dx.doi.org/10.1155/2015/620383] [PMID: 25737737]
[51]
Wang H, Liu Z, Li X, et al. Shikonin causes apoptosis by disrupting intracellular calcium homeostasis and mitochondrial function in human hepatoma cells. Exp Ther Med 2018; 15(2): 1484-92.
[http://dx.doi.org/10.3892/etm.2017.5591] [PMID: 29434733]
[52]
Shilnikova K, Piao MJ, Kang KA, et al. Shikonin induces mitochondria-mediated apoptosis and attenuates epithelial-mesenchymal transition in cisplatin-resistant human ovarian cancer cells. Oncol Lett 2018; 15(4): 5417-24.
[http://dx.doi.org/10.3892/ol.2018.8065] [PMID: 29563994]
[53]
Zhou G, Yang Z, Wang X, Tao R, Zhou Y. TRAIL enhances shikonin induced apoptosis through ROS/JNK signaling in cholangiocarcinoma cells. Cell Physiol Biochem 2017; 42(3): 1073-86.
[http://dx.doi.org/10.1159/000478758] [PMID: 28662515]
[54]
Liu CZ, Guo ZL, Li JZ. Application of shikonin compounds in preparation of drugs for promoting trail's anti-cancer activity. CN109223737, 2019.
[55]
Huang L, Xie H, Liu H. Endoplasmic reticulum stress, diabetes mellitus, and tissue injury. Curr Protein Pept Sci 2014; 15(8): 812-8.
[http://dx.doi.org/10.2174/1389203715666140930125426] [PMID: 25266908]
[56]
Liu Y, Kang X, Niu G, et al. Shikonin induces apoptosis and prosurvival autophagy in human melanoma A375 cells via ROS-mediated ER stress and p38 pathways. Artif Cells Nanomed Biotechnol 2019; 47(1): 626-35.
[http://dx.doi.org/10.1080/21691401.2019.1575229] [PMID: 30873870]
[57]
Han X, Kang KA, Piao MJ, et al. Shikonin exerts cytotoxic effects in human colon cancers by inducing apoptotic cell death via the endoplasmic reticulum and mitochondria-mediated pathways. Biomol Ther (Seoul) 2019; 27(1): 41-7.
[http://dx.doi.org/10.4062/biomolther.2018.047] [PMID: 29925224]
[58]
Shan ZL, Zhong L, Xiao CL, et al. Shikonin suppresses proliferation and induces apoptosis in human leukemia NB4 cells through modulation of MAPKs and c-Myc. Mol Med Rep 2017; 16(3): 3055-60.
[http://dx.doi.org/10.3892/mmr.2017.6965] [PMID: 28713949]
[59]
Zhao Q, Assimopoulou AN, Klauck SM, et al. Inhibition of c-MYC with involvement of ERK/JNK/MAPK and AKT pathways as a novel mechanism for shikonin and its derivatives in killing leukemia cells. Oncotarget 2015; 6(36): 38934-51.
[http://dx.doi.org/10.18632/oncotarget.5380] [PMID: 26472107]
[60]
Liu C, Zhang K, Shen H, Yao X, Sun Q, Chen G. Necroptosis: A novel manner of cell death, associated with stroke (Review). Int J Mol Med 2018; 41(2): 624-30.
[http://dx.doi.org/10.3892/ijmm.2017.3279] [PMID: 29207014]
[61]
Wang H, Sun L, Su L, et al. Mixed lineage kinase domain-like protein MLKL causes necrotic membrane disruption upon phosphorylation by RIP3. Mol Cell 2014; 54(1): 133-46.
[http://dx.doi.org/10.1016/j.molcel.2014.03.003] [PMID: 24703947]
[62]
Chen X, Li W, Ren J, et al. Translocation of mixed lineage kinase domain-like protein to plasma membrane leads to necrotic cell death. Cell Res 2014; 24(1): 105-21.
[http://dx.doi.org/10.1038/cr.2013.171] [PMID: 24366341]
[63]
Lee MJ, Kao SH, Hunag JE, et al. Shikonin time-dependently induced necrosis or apoptosis in gastric cancer cells via generation of reactive oxygen species. Chem Biol Interact 2014; 211: 44-53.
[http://dx.doi.org/10.1016/j.cbi.2014.01.008] [PMID: 24463199]
[64]
Agarwalla P, Banerjee R. N-end rule pathway inhibition assists colon tumor regression via necroptosis. Mol Ther Oncolytics 2016; 3: 16020.
[http://dx.doi.org/10.1038/mto.2016.20] [PMID: 27556106]
[65]
Shahsavari Z, Karami-Tehrani F, Salami S, Ghasemzadeh M. RIP1K and RIP3K provoked by shikonin induce cell cycle arrest in the triple negative breast cancer cell line, MDA-MB-468: Necroptosis as a desperate programmed suicide pathway. Tumour Biol 2016; 37(4): 4479-91.
[http://dx.doi.org/10.1007/s13277-015-4258-5] [PMID: 26496737]
[66]
Lu B, Gong X, Wang ZQ, et al. Shikonin induces glioma cell necroptosis in vitro by ROS overproduction and promoting RIP1/RIP3 necrosome formation. Acta Pharmacol Sin 2017; 38(11): 1543-53.
[http://dx.doi.org/10.1038/aps.2017.112] [PMID: 28816233]
[67]
Zhang Z, Zhang Z, Li Q, et al. Shikonin induces necroptosis by reactive oxygen species activation in nasopharyngeal carcinoma cell line CNE-2Z. J Bioenerg Biomembr 2017; 49(3): 265-72.
[http://dx.doi.org/10.1007/s10863-017-9714-z] [PMID: 28547157]
[68]
Sun W, Wu X, Gao H, et al. Cytosolic calcium mediates RIP1/RIP3 complex-dependent necroptosis through JNK activation and mitochondrial ROS production in human colon cancer cells. Free Radic Biol Med 2017; 108: 433-44.
[http://dx.doi.org/10.1016/j.freeradbiomed.2017.04.010] [PMID: 28414098]
[69]
Shahsavari Z, Karami-Tehrani F, Salami S. Targeting cell necroptosis and apoptosis induced by shikonin via receptor interacting protein kinases in estrogen receptor positive breast cancer cell line, MCF-7. Anticancer Agents Med Chem 2018; 18(2): 245-54.
[http://dx.doi.org/10.2174/1871520617666170919164055] [PMID: 28933271]
[70]
Chen C, Xiao W, Huang L, et al. Shikonin induces apoptosis and necroptosis in pancreatic cancer via regulating the expression of RIP1/RIP3 and synergizes the activity of gemcitabine. Am J Transl Res 2017; 9(12): 5507-17.
[PMID: 29312502]
[71]
Gary S. Cell cycle and growth control: Biomolecular regulation and cancer, second edition. J Cell Biochem 2004; 54(4): 373-452.
[http://dx.doi.org/10.1002/0471656437]
[72]
Zhong Y, Zheng XB, Cai KR, et al. Study of isobutyrylshikonin inhibiting proliferation of colon carcinoma cells through PI3K/Akt/m-TOR pathway. Zhongguo Zhongyao Zazhi 2018; 43(11): 2358-64.
[http://dx.doi.org/10.19540/j.cnki.cjcmm.20180130.001] [PMID: 29945391]
[73]
Lin KH, Huang MY, Cheng WC, et al. RNA-seq transcriptome analysis of breast cancer cell lines under shikonin treatment. Sci Rep 2018; 8(1): 2672-83.
[http://dx.doi.org/10.1038/s41598-018-21065-x] [PMID: 29422643]
[74]
Xu J, Guo Z, Wang QY, et al. Reversal effect of shikonin on cisplatin resistance of ovarian cancer SKOV3/DDP cells. Chin J Pathophysiol 2018; 34(9): 1616-21.
[http://dx.doi.org/10.3969/j.issn.1000-4718.2018.09.013]
[75]
Lu D, Qian J, Li W, Feng Q, Pan S, Zhang S. β-hydroxyisovaleryl-shikonin induces human cervical cancer cell apoptosis via PI3K/AKT/mTOR signaling. Oncol Lett 2015; 10(6): 3434-42.
[http://dx.doi.org/10.3892/ol.2015.3769] [PMID: 26788147]
[76]
Li MY, Mi C, Wang KS, et al. Shikonin suppresses proliferation and induces cell cycle arrest through the inhibition of hypoxia-inducible factor-1α signaling. Chem Biol Interact 2017; 274: 58-67.
[http://dx.doi.org/10.1016/j.cbi.2017.06.029] [PMID: 28684144]
[77]
Vukic MD, Vukovic NL, Obradovic AD, et al. Naphthoquinone rich Onosma visianii Clem (Boraginaceae) root extracts induce apoptosis and cell cycle arrest in HCT-116 and MDA-MB-231 cancer cell lines. Nat Prod Res 2018; 32(22): 2712-6.
[http://dx.doi.org/10.1080/14786419.2017.1374271] [PMID: 28882053]
[78]
Zhai T, Hei Z, Ma Q, et al. Shikonin induces apoptosis and G0/G1 phase arrest of gallbladder cancer cells via the JNK signaling pathway. Oncol Rep 2017; 38(6): 3473-80.
[http://dx.doi.org/10.3892/or.2017.6038] [PMID: 29039581]
[79]
Huang C, Hu G. Shikonin suppresses proliferation and induces apoptosis in endometrioid endometrial cancer cells via modulating miR-106b/PTEN/AKT/mTOR signaling pathway. Biosci Rep 2018; 38(2): BSR20171546.
[http://dx.doi.org/10.1042/BSR20171546] [PMID: 29449346]
[80]
Lin HY, Li ZK, Bai LF, et al. Synthesis of aryl dihydrothiazol acyl shikonin ester derivatives as anticancer agents through microtubule stabilization. Biochem Pharmacol 2015; 96(2): 93-106.
[http://dx.doi.org/10.1016/j.bcp.2015.04.021] [PMID: 25957661]
[81]
Dong ZG, Li MX, Zhao R, et al. Application of β, β’-Dimethacryloylakine in the preparation of anti-cancer drugs. CN110269852, 2019.
[82]
Dong ZG, Li MX, Zhao R, Huang H, Cui FR, Liu KD. Application of acetyl shikonin in preparation of drugs for preventing and treating colon cancer. CN110433150, 2019.
[83]
Zhang S, Gao Q, Li W, et al. Shikonin inhibits cancer cell cycling by targeting Cdc25s. BMC Cancer 2019; 19(1): 20.
[http://dx.doi.org/10.1186/s12885-018-5220-x] [PMID: 30616572]
[84]
Yu L, Chen Y, Tooze SA. Autophagy pathway: Cellular and molecular mechanisms. Autophagy 2018; 14(2): 207-15.
[http://dx.doi.org/10.1080/15548627.2017.1378838] [PMID: 28933638]
[85]
Kretschmer N, Deutsch A, Durchschein C, et al. Comparative gene expression analysis in WM164 melanoma cells revealed that β, β′-dimethylacrylshikonin leads to ROS generation, loss of mitochondrial membrane potential, and autophagy induction. Molecules 2018; 23(11): 2823-39.
[http://dx.doi.org/10.3390/molecules23112823] [PMID: 30380804]
[86]
Gong K, Zhang Z, Chen Y, Shu HB, Li W. Extracellular signal-regulated kinase, receptor interacting protein, and reactive oxygen species regulate shikonin-induced autophagy in human hepatocellular carcinoma. Eur J Pharmacol 2014; 738: 142-52.
[http://dx.doi.org/10.1016/j.ejphar.2014.05.034] [PMID: 24886888]
[87]
Song M, Zhang H, Chen Z, et al. Shikonin reduces hepatic fibrosis by inducing apoptosis and inhibiting autophagy via the platelet-activating factor-mitogen-activated protein kinase axis. Exp Ther Med 2021; 21(1): 28.
[http://dx.doi.org/10.3892/etm.2020.9460] [PMID: 33262814]
[88]
Kim HJ, Hwang KE, Park DS, et al. Shikonin-induced necroptosis is enhanced by the inhibition of autophagy in non-small cell lung cancer cells. J Transl Med 2017; 15(1): 123.
[http://dx.doi.org/10.1186/s12967-017-1223-7] [PMID: 28569199]
[89]
Gu MZ, Li XY, Tang XX. Effect of autophagy on the shikonin induced apoptosis of human medullary thyroid carcinoma TT cells. Int J Clin Exp Med 2016; 9(9): 17428-34.
[90]
Tang JC, Zhao J, Long F, et al. Efficacy of shikonin against esophageal cancer cells and its possible mechanisms in vitro and in vivo. J Cancer 2018; 9(1): 32-40.
[http://dx.doi.org/10.7150/jca.21224] [PMID: 29290767]
[91]
Hsieh YS, Liao CH, Chen WS, Pai JT, Weng MS. Shikonin inhibited migration and invasion of human lung cancer cells via suppression of c-Met-mediated epithelial-to-mesenchymal transition. J Cell Biochem 2017; 118(12): 4639-51.
[http://dx.doi.org/10.1002/jcb.26128] [PMID: 28485480]
[92]
Li X, Fan XX, Jiang ZB, et al. Shikonin inhibits gefitinib-resistant non-small cell lung cancer by inhibiting TrxR and activating the EGFR proteasomal degradation pathway. Pharmacol Res 2017; 115(5): 45-55.
[http://dx.doi.org/10.1016/j.phrs.2016.11.011] [PMID: 27864022]
[93]
Zhao Q, Kretschmer N, Bauer R, Efferth T. Shikonin and its derivatives inhibit the epidermal growth factor receptor signaling and synergistically kill glioblastoma cells in combination with erlotinib. Int J Cancer 2015; 137(6): 1446-56.
[http://dx.doi.org/10.1002/ijc.29483] [PMID: 25688715]
[94]
Li B, Yuan Z, Jiang J, Rao Y. Anti-tumor activity of Shikonin against afatinib resistant non-small cell lung cancer via negative regulation of PI3K/Akt signaling pathway. Biosci Rep 2018; 38(6): BSR20181693.
[http://dx.doi.org/10.1042/BSR20181693] [PMID: 30420490]
[95]
Jiang X, Wang J, Deng X, et al. The role of microenvironment in tumor angiogenesis. J Exp Clin Cancer Res 2020; 39(1): 204.
[http://dx.doi.org/10.1186/s13046-020-01709-5] [PMID: 32993787]
[96]
Yang L, Shen X, Li J, Yang J, Le Y, Gong Z. MicroRNAs affect tumor metastasis through regulating epithelial- mesenchymal transition. Yi Chuan 2014; 36(7): 637-45.
[http://dx.doi.org/10.3724/SP.J.1005.2014.0637] [PMID: 25076027]
[97]
Thompson EW, Newgreen DF, Tarin D. Carcinoma invasion and metastasis: A role for epithelial-mesenchymal transition? Cancer Res 2005; 65(14): 5991-5.
[http://dx.doi.org/10.1158/0008-5472.CAN-05-0616] [PMID: 16024595]
[98]
Gavert N, Ben-Ze’ev A. Epithelial-mesenchymal transition and the invasive potential of tumors. Trends Mol Med 2008; 14(5): 199-209.
[http://dx.doi.org/10.1016/j.molmed.2008.03.004] [PMID: 18406208]
[99]
Zhu JY, Wang HW, Qiu JF. The role of epithelial-mesenchymal transition in tumor metastasis. Chin J Biochem Mol Biol 2014; 30(12): 1169-75.
[http://dx.doi.org/10.13865/j.cnki.cjbmb.2014.12.02]
[100]
Yan H, Wang J. Research progress of epithelial-mesenchymal transition and tumor metastasis. China J Cancer Prev Treat 2010; 17(4): 311-4.
[http://dx.doi.org/10.16073/j.cnki.cjcpt.2010.04.016]
[101]
Zhang YH, Sun ZJ. Research progress of epidermal growth factor receptor and breast cancer. J Modern Oncol 2011; 19(7): 1454-6. 1672-4992-(2011)07-1454-03
[102]
Chen Y, Chen ZY, Chen L, et al. Shikonin inhibits triple-negative breast cancer-cell metastasis by reversing the epithelial-to-mesenchymal transition via glycogen synthase kinase 3β-regulated suppression of β-catenin signaling. Biochem Pharmacol 2019; 166: 33-45.
[http://dx.doi.org/10.1016/j.bcp.2019.05.001] [PMID: 31071331]
[103]
Conlon GA, Murray GI. Recent advances in understanding the roles of matrix metalloproteinases in tumour invasion and metastasis. J Pathol 2019; 247(5): 629-40.
[http://dx.doi.org/10.1002/path.5225] [PMID: 30582157]
[104]
Matias D, Balça-Silva J, Dubois LG, et al. Dual treatment with shikonin and temozolomide reduces glioblastoma tumor growth, migration and glial-to-mesenchymal transition. Cell Oncol (Dordr) 2017; 40(3): 247-61.
[http://dx.doi.org/10.1007/s13402-017-0320-1] [PMID: 28401486]
[105]
Zhang FY, Hu Y, Que ZY, et al. Shikonin inhibits the migration and invasion of human glioblastoma cells by targeting phosphorylated β-catenin and phosphorylated PI3K/Akt: A potential mechanism for the anti-glioma efficacy of a traditional Chinese herbal medicine. Int J Mol Sci 2015; 16(10): 23823-48.
[http://dx.doi.org/10.3390/ijms161023823] [PMID: 26473829]
[106]
Liu JP, Liu D, Gu JF, Zhu MM, Cui L. Shikonin inhibits the cell viability, adhesion, invasion and migration of the human gastric cancer cell line MGC-803 via the Toll-like receptor 2/nuclear factor-kappa B pathway. J Pharm Pharmacol 2015; 67(8): 1143-55.
[http://dx.doi.org/10.1111/jphp.12402] [PMID: 25880237]
[107]
Wen X, Li J, Cai D, et al. Anticancer efficacy of targeted shikonin liposomes modified with RGD in breast cancer cells. Molecules 2018; 23(2): 268-82.
[http://dx.doi.org/10.3390/molecules23020268] [PMID: 29382149]
[108]
Deng B, Qiu B. Shikonin inhibits invasiveness of osteosarcoma through MMP13 suppression. Tumour Biol 2015; 36(12): 9311-7.
[http://dx.doi.org/10.1007/s13277-015-3662-1] [PMID: 26104765]
[109]
Deng B, Feng Y, Deng B. TIPE2 mediates the suppressive effects of shikonin on MMP13 in osteosarcoma cells. Cell Physiol Biochem 2015; 37(6): 2434-43.
[http://dx.doi.org/10.1159/000438596] [PMID: 26650545]
[110]
Altenberg B, Greulich KO. Genes of glycolysis are ubiquitously overexpressed in 24 cancer classes. Genomics 2004; 84(6): 1014-20.
[http://dx.doi.org/10.1016/j.ygeno.2004.08.010] [PMID: 15533718]
[111]
Gao X, Wang H, Yang JJ, Liu X, Liu ZR. Pyruvate kinase M2 regulates gene transcription by acting as a protein kinase. Mol Cell 2012; 45(5): 598-609.
[http://dx.doi.org/10.1016/j.molcel.2012.01.001] [PMID: 22306293]
[112]
Yang W, Xia Y, Ji H, et al. Nuclear PKM2 regulates β-catenin transactivation upon EGFR activation. Nature 2011; 480(7375): 118-22.
[http://dx.doi.org/10.1038/nature10598] [PMID: 22056988]
[113]
Wang Y, Hao F, Nan Y, et al. PKM2 inhibitor shikonin overcomes the cisplatin resistance in bladder cancer by inducing necroptosis. Int J Biol Sci 2018; 14(13): 1883-91.
[http://dx.doi.org/10.7150/ijbs.27854] [PMID: 30443191]
[114]
Zhao X, Zhu Y, Hu J, et al. Shikonin inhibits tumor growth in mice by suppressing pyruvate kinase M2-mediated aerobic glycolysis. Sci Rep 2018; 8(1): 14517.
[http://dx.doi.org/10.1038/s41598-018-31615-y] [PMID: 30266938]
[115]
Chen J, Hu X, Cui J. Shikonin, vitamin K3 and vitamin K5 inhibit multiple glycolytic enzymes in MCF-7 cells. Oncol Lett 2018; 15(5): 7423-32.
[http://dx.doi.org/10.3892/ol.2018.8251] [PMID: 29725454]
[116]
Chai XX, Le YF, Wang JC, et al. Carpesium abrotanoides (L.) root as a potential source of natural anticancer compounds: Targeting glucose metabolism and PKM2/HIF 1-α axis of breast cancer cells. J Food Sci 2019; 84(12): 3825-32.
[http://dx.doi.org/10.1111/1750-3841.14953] [PMID: 31750963]
[117]
Chao TK, Huang TS, Liao YP, et al. Pyruvate kinase M2 is a poor prognostic marker of and a therapeutic target in ovarian cancer. PLoS One 2017; 12(7): e0182166.
[http://dx.doi.org/10.1371/journal.pone.0182166] [PMID: 28753677]
[118]
Ning X, Qi H, Li R, et al. Discovery of novel naphthoquinone derivatives as inhibitors of the tumor cell specific M2 isoform of pyruvate kinase. Eur J Med Chem 2017; 138: 343-52.
[http://dx.doi.org/10.1016/j.ejmech.2017.06.064] [PMID: 28688274]
[119]
Wu H, Zhao H, Chen L. Deoxyshikonin inhibits viability and glycolysis by suppressing the Akt/mTOR pathway in acute myeloid leukemia cells. Front Oncol 2020; 10: 1253.
[http://dx.doi.org/10.3389/fonc.2020.01253] [PMID: 32850379]
[120]
Song GY, Kim Y, Zheng XG, et al. Naphthazarin derivatives (IV): Synthesis, inhibition of DNA topoisomerase I and cytotoxicity of 2- or 6-acyl-5,8-dimethoxy-1, 4-naphthoquinones. Eur J Med Chem 2000; 35(3): 291-8.
[http://dx.doi.org/10.1016/S0223-5234(00)00129-X] [PMID: 10785555]
[121]
Cheng HM, Qiu YK, Wu Z, Zhao YF. DNA damage induced by shikonin in the presence of Cu(II) ions: Potential mechanism of its activity to apoptotic cell death. J Asian Nat Prod Res 2011; 13(1): 12-9.
[http://dx.doi.org/10.1080/10286020.2010.537262] [PMID: 21253945]
[122]
Plyta ZF, Li T, Papageorgiou VP, et al. Inhibition of topoisomerase I by naphthoquinone derivatives. Bioorg Med Chem Lett 1998; 8(23): 3385-90.
[http://dx.doi.org/10.1016/S0960-894X(98)00600-3] [PMID: 9873739]
[123]
Beretta GL, Ribaudo G, Menegazzo I, et al. Synthesis and evaluation of new naphthalene and naphthoquinone derivatives as anticancer agents. Arch Pharm (Weinheim) 2017; 350(1): 1155-67.
[http://dx.doi.org/10.1002/ardp.201600286] [PMID: 27990691]
[124]
Zhou Z, Lu B, Wang C, et al. RIP1 and RIP3 contribute to shikonin-induced DNA double-strand breaks in glioma cells via increase of intracellular reactive oxygen species. Cancer Lett 2017; 390(390): 77-90.
[http://dx.doi.org/10.1016/j.canlet.2017.01.004] [PMID: 28108311]
[125]
Wang Y, Zhou Y, Jia G, et al. Shikonin suppresses tumor growth and synergizes with gemcitabine in a pancreatic cancer xenograft model: Involvement of NF-κB signaling pathway. Biochem Pharmacol 2014; 88(3): 322-33.
[http://dx.doi.org/10.1016/j.bcp.2014.01.041] [PMID: 24522113]
[126]
Wang Z, Yin J, Li M, et al. Combination of shikonin with paclitaxel overcomes multidrug resistance in human ovarian carcinoma cells in a P-gp-independent manner through enhanced ROS generation. Chin Med 2019; 14: 7.
[http://dx.doi.org/10.1186/s13020-019-0231-3] [PMID: 30911326]
[127]
Wang J, Li Q, Wu JH, et al. Preparation of shikonin microemulsion modified by CD133 antibody and its anti-triple-negative breast cancer research. Chin Tradit Herbal Drugs 2019; 50(7): 1587-95.
[http://dx.doi.org/10.3969/j.issn.1000-4718.2018.09.013]
[128]
Shen Q, Fang TX, Li SS. Serum albumin nanoparticles loaded with anti-cancer active drugs and preparation. CN110898034, 2020.
[129]
Su YH, Huang YH, Li W, et al. Active targeting anti-cancer nanomicelles and preparation method and application. CN112237635, 2021.

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