[1] Lu, J.J.; Bao, J.L.; Wu, G.S.; Xu, W.S.; Huang, M.Q.; Chen, X.P.; Wang, Y.T. Quinones derived from plant secondary metabolites as anti-cancer agents. Anticancer Agents Med. Chem. 2013, 13, 456–463.
[2] Duval, J.; Pecher, V.; Poujol, M.; Lesellier, E. Research advances for the extraction, analysis and uses of anthraquinones: A review. Ind. Crop. Prod. 2016, 94, 812−833.
[3] Huang, Q.; Lu, G.D.; Shen, H.M.; Chung, M.C.; Ong, C.N. Anti-cancer properties of anthraquinones from rhubarb. Med. Res. Rev. 2007, 27, 609–630.
[4] López, L.I.L.; Flores, S.D.N.; Belmares, S.Y.S.; Galindo, A.S. Naphthoquinones: Biological properties and synthesis of lawsone and derivatives - A structured review. Vitae. 2014, 21, 248−258.
[5] Papageorgiou, V.P.; Assimopoulou, A.N.; Couladouros, E.A.; Hepworth, D.; Nicolaou, K.C. The chemistry and biology of alkannin, shikonin, and related naphthazarin natural products. Angew. Chem. Int. Ed. Engl. 1999, 38, 270–301.
[6] Verma, R.P. Anti-cancer activities of 1, 4-naphthoquinones: a QSAR study. Anticancer Agents Med. Chem. 2006, 6, 489–499.
[7] Wellington, K.W. Understanding cancer and the anticancer activities of naphthoquinones - A review. RSC Adv. 2015, 5, 20309−20338.
[8] Kayashima, T.; Mori, M.; Yoshida, H.; Mizushina, Y.; Matsubara, K. 1, 4-Naphthoquinone is a potent inhibitor of human cancer cell growth and angiogenesis. Cancer Lett. 2009, 278, 34–40.
[9] Prachayasittikul, V.; Pingaew, R.; Worachartcheewan, A.; Nantasenamat, C.; Prachayasittikul, S.; Ruchirawat, S.; Prachayasittikul, V. Synthesis, anticancer activity and QSAR study of 1, 4-naphthoquinone derivatives. Eur. J. Med. Chem. 2014, 84, 247–263.
[10] Benites, J.; Valderrama, J.A.; Bettega, K.; Pedrosa, R.C.; Calderon, P.B.; Verrax, J. Biological evaluation of donor-acceptor aminonaphthoquinones as antitumor agents. Eur. J. Med. Chem. 2010, 45, 6052–6057.
[11] Miranda-Filho, A.; Piñeros, M.; Bray, F. The descriptive epidemiology of lung cancer and tobacco control: a global overview 2018. Salud Publica Mex. 2019, 61, 219–229.
[12] Furrukh, M. Tobacco smoking and lung cancer: perception-changing facts. Sultan Qaboos Univ. Med. J. 2013, 13, 345–358.
[13] Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2018. CA Cancer J. Clin. 2018, 68, 7–30.
[14] Barney, J.N.; Tharayil, N.; DiTommaso, A.; Bhowmik, P.C. The biology of invasive alien plants in Canada. 5. Polygonum cuspidatum Sieb. & Zucc. [Fallopia japonica (Houtt.) Ronse Decr.]. Can. J. Plant Sci. 2006, 86, 887−906.
[15] Dong, X.; Fu, J.; Yin, X.; Cao, S.; Li, X.; Lin, L.; Huyiligeqi; Ni, J. Emodin: A review of its pharmacology, toxicity and pharmacokinetics. Phytother. Res. 2016, 30, 1207−1218.
[16] Dong, J.W.; Cai, L.; Fang, Y.S.; Duan, W.H.; Li, Z.J.; Ding, Z.T. Simultaneous, simple and rapid determination of five bioactive free anthraquinones in Radix et RhizomaRhei by quantitative 1H NMR. J. Braz. Chem. Soc. 2016, 27, 2120−2126.
[17] Wang, T.H.; Zhang, J.; Qiu, X.H.; Bai, J.Q.; Gao, Y.H.; Xu, W. Application of ultra-high-performance liquid chromatography coupled with LTQ-orbitrap mass spectrometry for the qualitative and quantitative analysis of polygonum multiflorum thumb. and its processed products. Molecules. 2015, 21, E40.
[18] Doogue, M.P.; Polasek, T.M. The ABCD of clinical pharmacokinetics. Ther. Adv. Drug Saf. 2013, 4, 5–7.
[19] Liu, W.; Feng, Q.; Li, Y.; Ye, L.; Hu, M.; Liu, Z.Q. Coupling of UDP-glucuronosyltransferases and multidrug resistance-associated proteins is responsible for the intestinal disposition and poor bioavailability of emodin. Toxicol. Appl. Pharmacol. 2012, 265, 316–324.
[20] Shia, C.S.; Hou, Y.C.; Tsai, S.Y.; Huieh, P.H.; Leu, Y.L.; Chao, P.D. Differences in pharmacokinetics and ex vivo antioxidant activity following intravenous and oral administrations of emodin to rats. J. Pharm. Sci. 2010, 99, 2185–2195.
[21] Di, X.; Wang, X.; Di, X.; Liu, Y.P. Effect of piperine on the bioavailability and pharmacokinetics of emodin in rats. J. Pharm. Biomed. Anal. 2015, 115, 144–149.
[22] He, L.; Bi, J.J.; Guo, Q.; Yu, Y.; Ye, X.F. Effects of emodin extracted from Chinese herbs on proliferation of non-small cell lung cancer and underlying mechanisms. Asian Pac. J. Cancer Prev. 2012, 13, 1505–1510.
[23] Kuo, Y.C.; Sun, C.M.; Ou, J.C.; Tsai, W.J. A tumor cell growth inhibitor from Polygonum hypoleucum Ohwi. Life Sci. 1997, 61, 2335–2344.
[24] Chan, T.C.; Chang, C.J.; Koonchanok, N.M.; Geahlen, R.L. Selective inhibition of the growth of ras-transformed human bronchial epithelial cells by emodin, a protein-tyrosine kinase inhibitor. Biochem. Biophys. Res. Commun. 1993, 193, 1152–1158.
[25] Lee, H.Z. Effects and mechanisms of emodin on cell death in human lung squamous cell carcinoma. Br. J. Pharmacol. 2001, 134, 11–20.
[26] Su, Y.T.; Chang, H.L.; Shyue, S.K.; Hsu, S.L. Emodin induces apoptosis in human lung adenocarcinoma cells through a reactive oxygen species-dependent mitochondrial signaling pathway. Biochem. Pharmacol. 2005, 70, 229–241.
[27] Fu, Z.Y.; Han, J.X.; Huang, H.Y. Effects of emodin on gene expression profile in small cell lung cancer NCI-H446 cells. Chin. Med. J. 2007, 120, 1710–1715.
[28] Chen, R.S.; Jhan, J.Y.; Su, Y.J.; Lee, W.T.; Cheng, C.M.; Ciou, S.C.; Lin, S.T.; Chuang, S.M.; Ko, J.C.; Lin, Y.W. Emodin enhances gefitinib-induced cytotoxicity via Rad51 down-regulation and ERK1/2 inactivation. Exper. Cell Res. 2009, 315, 2658−2672.
[29] Lai, J.M.; Chang, J.T.; Wen, C.L.; Hsu, S.L. Emodin induces a reactive oxygen species-dependent and ATM-p53-Bax mediated cytotoxicity in lung cancer cells. Eur. J. Pharmacol. 2009, 623, 1–9.
[30] Ko, J.C.; Su, Y.J.; Lin, S.T.; Jhan, J.Y.; Ciou, S.C.; Cheng, C.M.; Chiu, Y.F.; Kuo, Y.H.; Tsai, M.S.; Lin, Y.W. Emodin enhances cisplatin-induced cytotoxicity via down-regulation of ERCC1 and inactivation of ERK1/2. Lung Cancer. 2010, 69, 155–164.
[31] Ok, S.; Kim, S.M.; Kim, C.; Nam, D.; Shim, B.S.; Kim, S.H.; Ahn, K.S.; Choi, S.H.; Ahn, K.S. Emodin inhibits invasion and migration of prostate and lung cancer cells by down-regulating the expression of chemokine receptor CXCR4. Immunopharmacol. Immunotoxicol. 2012, 34, 768−778.
[32] Su, J.; Yan, Y.; Qu, J.K.; Xue, X.W.; Liu, Z.; Cai, H. Emodin induces apoptosis of lung cancer cells through ER stress and the TRIB3/NF-κB pathway. Oncol. Rep. 2017, 37, 1565–1572.
[33] Tang, Q.; Wu, J.J.; Zheng, F.; Hann, S.S.; Chen, Y.Q. Emodin increases expression of insulin-like growth factor binding protein 1 through activation of MEK/ERK/AMPKα and interaction of PPARγ and sp1 in lung cancer. Cell Physiol. Biochem. 2017, 41, 339–357.
[34] Wang, X.; Li, L.; Guan, R.J.; Zhu, D.N.; Song, N.N.; Shen, L.L. Emodin inhibits ATP-induced proliferation and migration by suppressing P2Y receptors in human lung adenocarcinoma cells. Cell Physiol. Biochem. 2017, 44, 1337–1351.
[35] Yuan, Y.; Liao, Q.W.; Xue, M.M.; Song, Z.J.; Tong, C.Y.; Tao, Z.G. Emodin: one main ingredient of shufeng jiedu capsule reverses chemoresistance of lung cancer cells through inhibition of EMT. Cell Physiol. Biochem. 2017, 42, 1063–1072.
[36] Haque, E.; Kamil, M.; Irfan, S.; Sheikh, S.; Hasan, A.; Nazir, A.; Mir, S.S. Blocking mutation independent p53 aggregation by emodin modulates autophagic cell death pathway in lung cancer. Int. J. Biochem. Cell Biol. 2018, 96, 90–95.
[37] Chen, S.F.; Zhang, Z.Y.; Zhang, J.L. Emodin enhances antitumor effect of paclitaxel on human non-small-cell lung cancer cells in vitro and in vivo. Drug Des. Dev. Ther. 2019, 13, 1145–1153.
[38] Li, Z.B.; Lin, Y.K.; Zhang, S.H.; Zhou, L.; Yan, G.X.; Wang, Y.H.; Zhang, M.D.; Wang, M.Q.; Lin, H.H.; Tong, Q.Z.; Duan, Y.J.; Du, G.J. Emodin regulates neutrophil phenotypes to prevent hypercoagulation and lung carcinogenesis. J. Transl. Med. 2019, 17, 90.
[39] Iwanowycz, S.; Wang, J.F.; Hodge, J.; Wang, Y.Z.; Yu, F.; Fan, D.P. Emodin inhibits breast cancer growth by blocking the tumor-promoting feedforward loop between cancer cells and macrophages. Mol. Cancer Ther. 2016, 15, 1931–1942.
[40] Saunders, I.T.; Mir, H.; Kapur, N.; Singh, S. Emodin inhibits colon cancer by altering BCL-2 family proteins and cell survival pathways. Cancer Cell Int. 2019, 19, 98.
[41] Wang, W.; Sun, Y.P.; Li, X.X.; Li, H.; Chen, Y.Y.; Tian, Y.; Yi, J.; Wang, J. Emodin potentiates the anticancer effect of cisplatin on gallbladder cancer cells through the generation of reactive oxygen species and the inhibition of survivin expression. Oncol. Rep. 2011, 26, 1143–1148.
[42] Zhou, J.; Li, G.; Han, G.; Feng, S.; Liu, Y.; Chen, J.; Liu, C.; Zhao, L.; Jin, F. Emodin induced necroptosis in the glioma cell line U251 via the TNF-α/RIP1/RIP3 pathway. Invest. New Drugs. 2019, https://doi.org/10.1007/ s10637-019-00764-w.
[43] Shieh, D.E.; Chen, Y.Y.; Yen, M.H.; Chiang, L.C.; Lin, C.C. Emodin-induced apoptosis through p53-dependent pathway in human hepatoma cells. Life Sci. 2004, 74, 2279–2290.
[44] Hsu, C.M.; Hsu, Y.A.; Tsai, Y.; Shieh, F.K.; Huang, S.H.; Wan, L.; Tsai, F.J. Emodin inhibits the growth of hepatoma cells: finding the common anti-cancer pathway using Huh7, Hep3B, and HepG2 cells. Biochem. Biophys. Res. Commun. 2010, 392, 473–478.
[45] Lin, W.F.; Zhong, M.F.; Liang, S.F.; Chen, Y.; Liu, D.; Yin, Z.F.; Cao, Q.X.; Wang, C.; Ling, C.Q. Emodin inhibits migration and invasion of MHCC-97H human hepatocellular carcinoma cells. Exp. Ther. Med. 2016, 12, 3369–3374.
[46] Lu, J.J.; Xu, Y.; Zhao, Z.; Ke, X.N.; Wei, X.; Kang, J.; Zong, X.; Mao, H.L.; Liu, P.S. Emodin suppresses proliferation, migration and invasion in ovarian cancer cells by down regulating ILK in vitro and in vivo. Onco Targets. Ther. 2017, 10, 3579–3589.
[47] Wei, W.T.; Chen, H.; Ni, Z.L.; Liu, H.B.; Tong, H.F.; Fan, L.; Liu, A.; Qiu, M.X.; Liu, D.L.; Guo, H.C.; Wang, Z.H.; Lin, S.Z. Antitumor and apoptosis-promoting properties of emodin, an anthraquinone derivative from Rheum officinale Baill, against pancreatic cancer in mice via inhibition of Akt activation. Int. J. Oncol. 2011, 39, 1381–1390.
[48] Cha, T.L.; Qiu, L.; Chen, C.T.; Wen, Y.; Hung, M.C. Emodin down-regulates androgen receptor and inhibits prostate cancer cell growth. Cancer Res. 2005, 65, 2287–2295.
[49] Boulos, J.C.; Rahama, M.; Hegazy, M.F.; Efferth, T. Shikonin derivatives for cancer prevention and therapy. Cancer Lett. 2019, 459, 248–267.
[50] Wang, R.B.; Yin, R.T.; Zhou, W.; Xu, D.F.; Li, S.S. Shikonin and its derivatives: a patent review. Expert Opin. Ther. Pat. 2012, 22, 977–997.
[51] Andújar, I.; Ríos, J.L.; Giner, R.M.; Recio, M.C. Pharmacological properties of shikonin - a review of literature since 2002. Planta Med. 2013, 79, 1685–1697.
[52] Chen, X.; Yang, L.; Oppenheim, J.J.; Howard, M.Z. Cellular pharmacology studies of shikonin derivatives. Phytother. Res. 2002, 16, 199–209.
[53] Huang, W.; Zhang, C.; Li, S.; Liang, Y.; Wang, H.; Chen, S. Online HPLC-DAD coupled with ESI-IT-TOF-MS and fluorescence detection to identify DNA-binding compounds from Lithospermum erythrorhizon using acridine orange as the fluorescence probe. J. Chin. Pharm. Sci. 2015, 24, 581–590.
[54] Yazaki, K. Lithospermum erythrorhizon cell cultures: Present and future aspects. Plant Biotechnol. (Tokyo) 2017, 34, 131–142.
[55] Zhu, G.; Riedl, H.; Kamelin, R. Lithospermum (Boraginaceae). Flora China. 1995, 16, 342−344.
[56] Wang, R.B.; Yin, R.T.; Zhou, W.; Xu, D.F.; Li, S.S. Shikonin and its derivatives: a patent review. Expert Opin. Ther. Pat. 2012, 22, 977–997.
[57] Chen, X.; Yang, L.; Oppenheim, J.J.; Howard, M.Z. Cellular pharmacology studies of shikonin derivatives. Phytother. Res. 2002, 16, 199–209.
[58] Albreht, A.; Vovk, I.; Simonovska, B. Addition of β-lactoglobulin produces water-soluble shikonin. J. Agric. Food Chem. 2012, 60, 10834–10843.
[59] Assimopoulou, A.N.; Papageorgiou, V.P.; Kiparissides, C. Synthesis and release studies of shikonin-containing microcapsules prepared by the solvent evaporation method. J. Microencapsul. 2003, 20, 581–596.
[60] Wang, F.F.; Yao, X.S.; Zhang, Y.W.; Tang, J.S. Synthesis, biological function and evaluation of Shikonin in cancer therapy. Fitoterapia. 2019, 134, 329–339.
[61] Lin, H.Y.; Li, Z.K.; Bai, L.F.; Baloch, S.K.; Wang, F.; Qiu, H.Y.; Wang, X.; Qi, J.L.; Yang, R.W.; Wang, X.M.; Yang, Y.H. Synthesis of aryl dihydrothiazol acyl shikonin ester derivatives as anticancer agents through microtubule stabilization. Biochem. Pharmacol. 2015, 96, 93–106.
[62] Baloch, S.K.; Ling, L.J.; Qiu, H.Y.; Ma, L.; Lin, H.Y.; Huang, S.C.; Qi, J.L.; Wang, X.M.; Lu, G.H.; Yang, Y.H. Synthesis and biological evaluation of novel shikonin ester derivatives as potential anti-cancer agents. RSC Adv. 2014, 4, 35588−35596.
[63] Wang, R.B.; Zhang, X.; Song, H.L.; Zhou, S.S.; Li, S.S. Synthesis and evaluation of novel alkannin and shikonin oxime derivatives as potent antitumor agents. Bioorg. Med. Chem. Lett. 2014, 24, 4304–4307.
[64] Wang, H.Y.; Wu, C.L.; Wan, S.B.; Zhang, H.J.; Zhou, S.W.; Liu, G.T. Shikonin attenuates lung cancer cell adhesion to extracellular matrix and metastasis by inhibiting integrin β1 expression and the ERK1/2 signaling pathway. Toxicology. 2013, 308, 104–112.
[65] Lan, W.J.; Wan, S.B.; Gu, W.Q.; Wang, H.Y.; Zhou, S.W. Mechanisms behind the inhibition of lung adenocarcinoma cell by shikonin. Cell Biochem. Biophys. 2014, 70, 1459–1467.
[66] Qu, D.; Chen, Y.U.; Xu, X.M.; Zhang, M.; Zhang, Y.I.; Li, S.Q. Cbl-b-regulated extracellular signal-regulated kinase signalling is involved in the shikonin-induced apoptosis of lung cancer cells in vitro. Exper. Ther. Med. 2015, 9, 1265−1270.
[67] Yeh, Y.C.; Liu, T.J.; Lai, H.C. 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.
[68] Jeung, Y.J.; Kim, H.G.; Ahn, J.; Lee, H.J.; Lee, S.B.; Won, M.; Jung, C.R.; Im, J.Y.; Kim, B.K.; Park, S.K.; Son, M.J. Shikonin induces apoptosis of lung cancer cells via activation of FOXO3a/EGR1/SIRT1 signalling antagonized by p300. Biochim. Biophy. Acta (BBA) - Mol. Cell Res. 2016, 1863, 2584−2593.
[69] Hsieh, Y.S.; Liao, C.H.; Chen, W.S.; Pai, J.T.; Weng, M.S. 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, 4639–4651.
[70] Kim, H.J.; Hwang, K.E.; Park, D.S.; Oh, S.H.; Jun, H.Y.; Yoon, K.H.; Jeong, E.T.; Kim, H.R.; Kim, Y.S. Shikonin-induced necroptosis is enhanced by the inhibition of autophagy in non-small cell lung cancer cells. J Transl. Med. 2017, 15, 123.
[71] Li, X.; Fan, X.X.; Jiang, Z.B.; Loo, W.T.; Yao, X.J.; Leung, E.L.; Chow, L.W.; Liu, L. Shikonin inhibits gefitinib-resistant non-small cell lung cancer by inhibiting TrxR and activating the EGFR proteasomal degradation pathway. Pharmacol. Res. 2017, 115, 45–55.
[72] Liu, X.C.; Sun, G.Y. Shikonin enhances Adriamycin antitumor effects by inhibiting efflux pumps in A549 cells. Oncol. Lett. 2017, 14, 4270–4276.
[73] Li, Y.L.; Hu, X.; Li, Q.Y.; Wang, F.; Zhang, B.; Ding, K.; Tan, B.Q.; Lin, N.M.; Zhang, C. Shikonin sensitizes wild-type EGFR NSCLC cells to erlotinib and gefitinib therapy. Mol. Med. Rep. 2018, 18, 3882−3890.
[74] Tang, J.C.; Ren, Y.G.; Zhao, J.; Long, F.; Chen, J.Y.; Jiang, Z. Shikonin enhances sensitization of gefitinib against wild-type EGFR non-small cell lung cancer via inhibition PKM2/stat3/cyclinD1 signal pathway. Life Sci. 2018, 204, 71–77.
[75] Guo, X.P.; Zhang, X.Y.; Zhang, S.D. Clinical trial on the effects of shikonin mixture on later stage lung cancer. Chin. J. Mod. Dev. Tradit. Med. 1991, 11, 598–599.
[76] Chen, Y.; Chen, Z.Y.; Chen, L.; Zhang, J.Y.; Fu, L.Y.; Tao, L.; Zhang, Y.; Hu, X.X.; Shen, X.C. 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.
[77] He, G.D.; He, G.L.; Zhou, R.Y.; Pi, Z.B.; Zhu, T.Q.; Jiang, L.M.; Xie, Y.B. Enhancement of cisplatin-induced colon cancer cells apoptosis by shikonin, a natural inducer of ROS in vitro and in vivo. Biochem. Biophys. Res. Commun. 2016, 469, 1075–1082.
[78] Zhang, L.L.; Zhan, L.; Jin, Y.D.; Min, Z.L.; Wei, C.; Wang, Q.; Chen, Y.J.; Wu, Q.M.; Hu, X.M.; Yuan, Q. SIRT2 mediated antitumor effects of shikonin on metastatic colorectal cancer. Eur. J. Pharmacol. 2017, 797, 1–8.
[79] Zhai, T.; Hei, Z.Y.; Ma, Q.; Liang, H.B.; Xu, Y.; Zhang, Y.C.; Jin, L.Y.; Han, C.; Wang, J.D. Shikonin induces apoptosis and G0/G1 phase arrest of gallbladder cancer cells via the JNK signaling pathway. Oncol. Rep. 2017, 38, 3473–3480.
[80] Huang, C.; Luo, Y.; Zhao, J.; Yang, F.; Zhao, H.; Fan, W.; Ge, P. Shikonin kills glioma cells through necroptosis mediated by RIP-1. PLoS One. 2013, 8, e66326.
[81] Wang, Y.W.; Zhou, Y.N.; Jia, G.; Han, B.; Liu, J.; Teng, Y.Q.; Lv, J.; Song, Z.F.; Li, Y.L.; Ji, L.; Pan, S.H.; Jiang, H.C.; Sun, B. Shikonin suppresses tumor growth and synergizes with gemcitabine in a pancreatic cancer xenograft model: Involvement of NF-κB signaling pathway. Biochem. Pharmacol. 2014, 88, 322–333.
[82] Chen, Y.Q.; Zheng, L.; Liu, J.Q.; Zhou, Z.H.; Cao, X.L.; Lv, X.; Chen, F.X. Shikonin inhibits prostate cancer cells metastasis by reducing matrix metalloproteinase-2/-9 expression via AKT/mTOR and ROS/ERK1/2 pathways. Int. Immunopharmacol. 2014, 21, 447–455.
[83] Tian, R.; Li, Y.; Gao, M. Shikonin causes cell-cycle arrest and induces apoptosis by regulating the EGFR-NF-κB signalling pathway in human epidermoid carcinoma A431 cells. Biosci. Rep. 2015, 35, e00189. |