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Current Pharmaceutical Biotechnology

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ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

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Mini-Review Article

The Natural Product Oridonin as an Anticancer Agent: Current Achievements and Problems

Author(s): Xiangyan Hu, Sisi Huang, Shiying Ye and Jinhuan Jiang*

Volume 25, Issue 6, 2024

Published on: 04 September, 2023

Page: [655 - 664] Pages: 10

DOI: 10.2174/1389201024666230821110116

Price: $65

Abstract

Oridonin, an active diterpenoid isolated from traditional Chinese herbal medicine, has received a rising attention for its remarkable roles in cancer therapy. In recent years, increasing evidences have revealed that oridonin inhibits the occurrence and development of tumor cells through multiple mechanisms, including induction of apoptosis and autophagy, cell cycle arrest, and inhibition of angiogenesis as well as migration and invasion. In addition, several molecular signal targets have been identified, including ROS, EGFR, NF-κB, PI3K/Akt, and MAPK. In this paper, we review considerable knowledge about the molecular mechanisms and signal targets of oridonin, which has been studied in recent years. It is expected that oridonin may be developed as a novel anti-tumor herbal medicine in human cancer treatment

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Graphical Abstract

[1]
Abelson, P.H. Medicine from plants. Science, 1990, 247(4942), 513.
[http://dx.doi.org/10.1126/science.2300807] [PMID: 2300807]
[2]
Abdullah, N.A.; Md Hashim, N.F.; Ammar, A.; Muhamad Zakuan, N. An insight into the anti-angiogenic and anti-metastatic effects of oridonin: Current knowledge and future potential. Molecules, 2021, 26(4), 775.
[http://dx.doi.org/10.3390/molecules26040775] [PMID: 33546106]
[3]
Owona, B.A.; Schluesener, H.J. Molecular insight in the multifunctional effects of oridonin. Drugs R D., 2015, 15(3), 233-244.
[http://dx.doi.org/10.1007/s40268-015-0102-z] [PMID: 26290464]
[4]
Liu, W.; Huang, G.; Yang, Y.; Gao, R.; Zhang, S.; Kou, B. Oridonin inhibits epithelial-mesenchymal transition of human nasopharyngeal carcinoma cells by negatively regulating AKT/STAT3 signaling pathway. Int. J. Med. Sci., 2021, 18(1), 81-87.
[http://dx.doi.org/10.7150/ijms.48552] [PMID: 33390776]
[5]
Sobral, P.J.M.; Vicente, A.T.S.; Salvador, J.A.R. Recent advances in oridonin derivatives with anticancer activity. Front Chem., 2023, 11, 1066280.
[http://dx.doi.org/10.3389/fchem.2023.1066280] [PMID: 36846854]
[6]
Xu, J.; Wold, E.; Ding, Y.; Shen, Q.; Zhou, J. Therapeutic potential of oridonin and its analogs: From anticancer and antiinflammation to neuroprotection. Molecules, 2018, 23(2), 474.
[http://dx.doi.org/10.3390/molecules23020474] [PMID: 29470395]
[7]
Zhao, X.; Zhang, Q.; Wang, Y.; Li, S.; Yu, X.; Wang, B.; Wang, X. Oridonin induces autophagy-mediated cell death in pancreatic cancer by activating the c-Jun N-terminal kinase pathway and inhibiting phosphoinositide 3-kinase signaling. Ann. Transl. Med., 2021, 9(13), 1084.
[http://dx.doi.org/10.21037/atm-21-2630] [PMID: 34422996]
[8]
Zhou, J.; Li, Y.; Shi, X.; Hao, S.; Zhang, F.; Guo, Z.; Gao, Y.; Guo, H.; Liu, L. Oridonin inhibits tumor angiogenesis and induces vessel normalization in experimental colon cancer. J. Cancer, 2021, 12(11), 3257-3264.
[http://dx.doi.org/10.7150/jca.55929] [PMID: 33976735]
[9]
Jin, X.; Xu, J.; Yang, F.; Chen, J.; Luo, F.; Xu, B.; Xu, J. Oridonin attenuates thioacetamide-induced osteoclastogenesis through mapk/nf-κb pathway and thioacetamide-inhibited osteoblastogenesis through BMP-2/RUNX2 Pathway. Calcif. Tissue Int., 2023, 112(6), 704-715.
[http://dx.doi.org/10.1007/s00223-023-01080-5] [PMID: 37032340]
[10]
Chen, G.; Yang, Z.; Wen, D.; Li, P.; Xiong, Q.; Wu, C. Oridonin inhibits mycobacterium marinum infection-induced oxidative stress in vitro and in vivo. Pathogens., 2023, 12(6), 799.
[http://dx.doi.org/10.3390/pathogens12060799] [PMID: 37375489]
[11]
Zhang, Z.; Zhang, H.; Zhang, Y.; Zhang, Q.; Liu, Q.; Hu, Y.; Chen, X.; Wang, J.; Shi, Y.; Deng, C.; Gong, P.; Zhang, B.; Li, X.; Zhu, B.; Ye, H. Oridonin inhibits SARS-CoV-2 replication by targeting viral proteinase and polymerase. Virol. Sin., 2023, 38(3), 470-479.
[http://dx.doi.org/10.1016/j.virs.2023.04.008] [PMID: 37127212]
[12]
Kazantseva, L.; Becerra, J.; Santos-Ruiz, L. Oridonin enhances antitumor effects of doxorubicin in human osteosarcoma cells. Pharmacol. Rep., 2022, 74(1), 248-256.
[http://dx.doi.org/10.1007/s43440-021-00324-1] [PMID: 34427908]
[13]
Jiang, J.H.; Pi, J.; Cai, J.Y. Oridonin exhibits anti-angiogenic activity in human umbilical vein endothelial cells by inhibiting VEGF-induced VEGFR-2 signaling pathway. Pathol. Res. Pract., 2020, 216(8), 153031.
[http://dx.doi.org/10.1016/j.prp.2020.153031] [PMID: 32703495]
[14]
Zhao, Y.; Xiao, W.; Peng, W.; Huang, Q.; Wu, K.; Evans, C.E.; Liu, X.; Jin, H. Oridonin-loaded nanoparticles inhibit breast cancer progression through regulation of ros-related nrf2 signaling pathway. Front. Bioeng. Biotechnol., 2021, 9, 600579.
[http://dx.doi.org/10.3389/fbioe.2021.600579] [PMID: 33898397]
[15]
Gui, Y.; Cheng, J.; Chen, Z. Oridonin improves the therapeutic effect of lentinan on lung cancer. Exp. Ther. Med., 2021, 22(2), 886.
[http://dx.doi.org/10.3892/etm.2021.10318] [PMID: 34194564]
[16]
Chen, F.; Liao, J.; Wu, P.; Cheng, L.; Ma, Y.; Zhang, L.; Leng, X.; Zhu, X.; Liu, Z.; Xie, F. Oridonin inhibits the occurrence and development of colorectal cancer by reversing the Warburg effect via reducing PKM2 dimer formation and preventing its entry into the nucleus. Eur. J. Pharmacol., 2023, 954, 175856.
[http://dx.doi.org/10.1016/j.ejphar.2023.175856] [PMID: 37321470]
[17]
Liu, X.; Xu, J.; Zhou, J.; Shen, Q. Oridonin and its derivatives for cancer treatment and overcoming therapeutic resistance. Genes Dis., 2021, 8(4), 448-462.
[http://dx.doi.org/10.1016/j.gendis.2020.06.010] [PMID: 34179309]
[18]
Yang, J.; Ren, X.; Zhang, L.; Li, Y.; Cheng, B.; Xia, J. Oridonin inhibits oral cancer growth and PI3K/Akt signaling pathway. Biomed. Pharmacother., 2018, 100, 226-232.
[http://dx.doi.org/10.1016/j.biopha.2018.02.011] [PMID: 29432993]
[19]
Wang, H.; Zhu, L.; Feng, X.; Zhang, H.; Luo, Q.; Chen, F. Oridonin induces G2/M cell cycle arrest and apoptosis in human oral squamous cell carcinoma. Eur. J. Pharmacol., 2017, 815, 282-289.
[http://dx.doi.org/10.1016/j.ejphar.2017.09.021] [PMID: 28935563]
[20]
Bohanon, F.J.; Wang, X.; Graham, B.M.; Prasai, A.; Vasudevan, S.J.; Ding, C.; Ding, Y.; Radhakrishnan, G.L.; Rastellini, C.; Zhou, J.; Radhakrishnan, R.S. Enhanced anti-fibrogenic effects of novel oridonin derivative CYD0692 in hepatic stellate cells. Mol. Cell. Biochem., 2015, 410(1-2), 293-300.
[http://dx.doi.org/10.1007/s11010-015-2562-4] [PMID: 26346163]
[21]
Bu, H.Q.; Liu, D.L.; Wei, W.T.; Chen, L.; Huang, H.; Li, Y.; Cui, J.H. Oridonin induces apoptosis in SW1990 pancreatic cancer cells via p53- and caspase-dependent induction of p38 MAPK. Oncol. Rep., 2014, 31(2), 975-982.
[http://dx.doi.org/10.3892/or.2013.2888] [PMID: 24297112]
[22]
Tian, L.; Xie, K.; Sheng, D.; Wan, X.; Zhu, G. Antiangiogenic effects of oridonin. BMC Complement. Altern. Med., 2017, 17(1), 192.
[http://dx.doi.org/10.1186/s12906-017-1706-3] [PMID: 28376864]
[23]
Yang, Q.; Ma, W.; Yu, K.; Zhang, Q.; Ye, Z.; Xia, W.; Li, S. Oridonin suppresses human gastric cancer growth in vitro and in vivovia Inhibition of VEGF, Integrin β3, and PCNA. Biol. Pharm. Bull., 2020, 43(7), 1035-1045.
[http://dx.doi.org/10.1248/bpb.b19-00839] [PMID: 32612067]
[24]
Xu, L.; Bi, Y.; Xu, Y.; Zhang, Z.; Xu, W.; Zhang, S.; Chen, J. Oridonin inhibits the migration and epithelial-to-mesenchymal transition of small cell lung cancer cells by suppressing FAK-ERK1/2 signalling pathway. J. Cell. Mol. Med., 2020, 24(8), 4480-4493.
[http://dx.doi.org/10.1111/jcmm.15106] [PMID: 32168416]
[25]
Sun, Y.; Jiang, X.; Lu, Y.; Zhu, J.; Yu, L.; Ma, B.; Zhang, Q. Oridonin prevents epithelial-mesenchymal transition and TGF-β1-induced epithelial-mesenchymal transition by inhibiting TGF-β1/Smad2/3 in osteosarcoma. Chem. Biol. Interact., 2018, 296, 57-64.
[http://dx.doi.org/10.1016/j.cbi.2018.09.013] [PMID: 30243739]
[26]
Liu, Q.Q.; Chen, K.; Ye, Q.; Jiang, X.H.; Sun, Y.W. Oridonin inhibits pancreatic cancer cell migration and epithelial-mesenchymal transition by suppressing Wnt/β-catenin signaling pathway. Cancer Cell Int., 2016, 16(1), 57.
[http://dx.doi.org/10.1186/s12935-016-0336-z] [PMID: 27453691]
[27]
Li, C.Y.; Wang, Q.; Shen, S.; Wei, X.L.; Li, G.X. Oridonin inhibits migration, invasion, adhesion and TGF-β1-induced epithelial-mesenchymal transition of melanoma cells by inhibiting the activity of PI3K/Akt/GSK-3β signaling pathway. Oncol. Lett., 2018, 15(1), 1362-1372.
[PMID: 29399187]
[28]
Du, Y.; Zhang, J.; Yan, S.; Tao, Z.; Wang, C.; Huang, M.; Zhang, X. Oridonin inhibits the proliferation, migration and invasion of human osteosarcoma cells via suppression of matrix metalloproteinase expression and STAT3 signalling pathway. J. BUON, 2019, 24(3), 1175-1180.
[PMID: 31424676]
[29]
Chen, K.; Ye, J.; Qi, L.; Liao, Y.; Li, R.; Song, S.; Zhou, C.; Feng, R.; Zhai, W. Oridonin inhibits hypoxia-induced epithelial–mesenchymal transition and cell migration by the hypoxia-inducible factor-1α/matrix metallopeptidase-9 signal pathway in gallbladder cancer. Anticancer Drugs, 2019, 30(9), 925-932.
[http://dx.doi.org/10.1097/CAD.0000000000000797] [PMID: 31517732]
[30]
Santavanond, J.P.; Rutter, S.F.; Atkin-Smith, G.K.; Poon, I.K.H. Apoptotic bodies: Mechanism of formation, isolation and functional relevance. Subcell. Biochem., 2021, 97, 61-88.
[http://dx.doi.org/10.1007/978-3-030-67171-6_4] [PMID: 33779914]
[31]
Jeon, M.Y.; Seo, S.U.; Woo, S.M.; Min, K.; Byun, H.S.; Hur, G.M.; Kang, S.C.; Kwon, T.K. Oridonin enhances TRAIL-induced apoptosis through GALNT14-mediated DR5 glycosylation. Biochimie., 2019, 165, 108-114.
[http://dx.doi.org/10.1016/j.biochi.2019.07.015] [PMID: 31336136]
[32]
Gu, Z.; Wang, X.; Qi, R.; Wei, L.; Huo, Y.; Ma, Y.; Shi, L.; Chang, Y.; Li, G.; Zhou, L. Oridonin induces apoptosis in uveal melanoma cells by upregulation of Bim and downregulation of Fatty Acid Synthase. Biochem. Biophys. Res. Commun., 2015, 457(2), 187-193.
[http://dx.doi.org/10.1016/j.bbrc.2014.12.086] [PMID: 25545058]
[33]
Lu, Y.; Sun, Y.; Zhu, J.; Yu, L.; Jiang, X.; Zhang, J.; Dong, X.; Ma, B.; Zhang, Q. Oridonin exerts anticancer effect on osteosarcoma by activating PPAR-γ and inhibiting Nrf2 pathway. Cell Death Dis., 2018, 9(1), 15.
[http://dx.doi.org/10.1038/s41419-017-0031-6] [PMID: 29323103]
[34]
Gao, S.; Tan, H.; Zhu, N.; Gao, H.; Lv, C.; Gang, J.; Ji, Y. Oridonin induces apoptosis through the mitochondrial pathway in human gastric cancer SGC-7901 cells. Int. J. Oncol., 2016, 48(6), 2453-2460.
[http://dx.doi.org/10.3892/ijo.2016.3479] [PMID: 27082253]
[35]
Jiang, J.H.; Pi, J.; Jin, H.; Cai, J.Y. Oridonin-induced mitochondria-dependent apoptosis in esophageal cancer cells by inhibiting PI3K/AKT/mTOR and Ras/Raf pathways. J. Cell. Biochem., 2019, 120(3), 3736-3746.
[http://dx.doi.org/10.1002/jcb.27654] [PMID: 30229997]
[36]
Kou, B.; Yang, Y.; Bai, Y.E.; Shi, Y.H.; Gao, R.X.; Yang, F.L.; Zhang, S.Q.; Liu, W. Oridonin induces apoptosis of laryngeal carcinoma via endoplasmic reticulum stress. Cancer Manag. Res., 2020, 12, 8387-8396.
[http://dx.doi.org/10.2147/CMAR.S271759] [PMID: 32982432]
[37]
Yao, Z.; Xie, F.; Li, M.; Liang, Z.; Xu, W.; Yang, J.; Liu, C.; Li, H.; Zhou, H.; Qu, L.H. Oridonin induces autophagy via inhibition of glucose metabolism in p53-mutated colorectal cancer cells. Cell Death Dis., 2017, 8(2), e2633.
[http://dx.doi.org/10.1038/cddis.2017.35] [PMID: 28230866]
[38]
Chang, H.; Zou, Z. Targeting autophagy to overcome drug resistance: Further developments. J. Hematol. Oncol., 2020, 13(1), 159.
[http://dx.doi.org/10.1186/s13045-020-01000-2] [PMID: 33239065]
[39]
Mizushima, N.; Levine, B. Autophagy in human diseases. N. Engl. J. Med., 2020, 383(16), 1564-1576.
[http://dx.doi.org/10.1056/NEJMra2022774] [PMID: 33053285]
[40]
Cao, S.; Huang, Y.; Zhang, Q.; Lu, F.; Donkor, P.O.; Zhu, Y.; Qiu, F.; Kang, N. Molecular mechanisms of apoptosis and autophagy elicited by combined treatment with oridonin and cetuximab in laryngeal squamous cell carcinoma. Apoptosis, 2019, 24(1-2), 33-45.
[http://dx.doi.org/10.1007/s10495-018-1497-0] [PMID: 30430397]
[41]
Bu, H.; Liu, D.; Zhang, G.; Chen, L.; Song, Z. AMPK/mTOR/ULK1 Axis-mediated pathway participates in apoptosis and autophagy induction by oridonin in colon cancer DLD-1 Cells. OncoTargets Ther., 2020, 13, 8533-8545.
[http://dx.doi.org/10.2147/OTT.S262022] [PMID: 32904616]
[42]
Yang, H.; Gao, Y.; Fan, X.; Liu, X.; Peng, L.; Ci, X. Oridonin sensitizes cisplatin-induced apoptosis via AMPK/Akt/mTOR-Dependent autophagosome accumulation in A549 Cells. Front. Oncol., 2019, 9, 769.
[http://dx.doi.org/10.3389/fonc.2019.00769] [PMID: 31475112]
[43]
Li, D.; Cui, Q.; Chen, S.; Wu, L.; Tashiro, S.; Onodera, S.; Ikejima, T. Inactivation of ras and changes of mitochondrial membrane potential contribute to oridonin-induced autophagy in a431 cells. J. Pharmacol. Sci., 2007, 105(1), 22-33.
[http://dx.doi.org/10.1254/jphs.FPJ06022X] [PMID: 17895587]
[44]
Fuloria, S.; Subramaniyan, V.; Karupiah, S.; Kumari, U.; Sathasivam, K.; Meenakshi, D.U.; Wu, Y.S.; Sekar, M.; Chitranshi, N.; Malviya, R.; Sudhakar, K.; Bajaj, S.; Fuloria, N.K. Comprehensive review of methodology to detect reactive oxygen species (ROS) in mammalian species and establish its relationship with antioxidants and cancer. Antioxidants, 2021, 10(1), 128.
[http://dx.doi.org/10.3390/antiox10010128] [PMID: 33477494]
[45]
Fan, X.; Xie, M.; Zhao, F.; Li, J.; Fan, C.; Zheng, H.; Wei, Z.; Ci, X.; Zhang, S. Daphnetin triggers ROS-induced cell death and induces cytoprotective autophagy by modulating the AMPK/Akt/mTOR pathway in ovarian cancer. Phytomedicine, 2021, 82, 153465.
[http://dx.doi.org/10.1016/j.phymed.2021.153465] [PMID: 33486268]
[46]
Pathania, D.; Sechi, M.; Palomba, M.; Sanna, V.; Berrettini, F.; Sias, A.; Taheri, L.; Neamati, N. Design and discovery of novel quinazolinedione-based redox modulators as therapies for pancreatic cancer. Biochim. Biophys. Acta, Gen. Subj., 2014, 1840(1), 332-343.
[http://dx.doi.org/10.1016/j.bbagen.2013.08.005] [PMID: 23954204]
[47]
Oh, H.N.; Seo, J.H.; Lee, M.H.; Yoon, G.; Cho, S.S.; Liu, K.; Choi, H.; Oh, K.B.; Cho, Y.S.; Kim, H.; Han, A.L.; Chae, J.I.; Shim, J.H. Oridonin induces apoptosis in oral squamous cell carcinoma probably through the generation of reactive oxygen species and the p38/JNK MAPK pathway. Int. J. Oncol., 2018, 52(5), 1749-1759.
[http://dx.doi.org/10.3892/ijo.2018.4319] [PMID: 29568920]
[48]
Zhang, D.; Zhou, Q.; Huang, D.; He, L.; Zhang, H.; Hu, B.; Peng, H.; Ren, D. ROS/JNK/c-Jun axis is involved in oridonin-induced caspase-dependent apoptosis in human colorectal cancer cells. Biochem. Biophys. Res. Commun., 2019, 513(3), 594-601.
[http://dx.doi.org/10.1016/j.bbrc.2019.04.011] [PMID: 30981511]
[49]
Xue, D.; Zhou, X.; Qiu, J. Emerging role of NRF2 in ROS-mediated tumor chemoresistance. Biomed. Pharmacother., 2020, 131, 110676.
[http://dx.doi.org/10.1016/j.biopha.2020.110676] [PMID: 32858502]
[50]
Wee, P.; Wang, Z. Epidermal growth factor receptor cell proliferation signaling pathways. Cancers, 2017, 9(5), 52.
[http://dx.doi.org/10.3390/cancers9050052] [PMID: 28513565]
[51]
Sigismund, S.; Avanzato, D.; Lanzetti, L. Emerging functions of the EGFR in cancer. Mol. Oncol., 2018, 12(1), 3-20.
[http://dx.doi.org/10.1002/1878-0261.12155] [PMID: 29124875]
[52]
Wu, M.; Zhang, P. EGFR-mediated autophagy in tumourigenesis and therapeutic resistance. Cancer Lett., 2020, 469, 207-216.
[http://dx.doi.org/10.1016/j.canlet.2019.10.030] [PMID: 31639425]
[53]
Tumbrink, H.L.; Heimsoeth, A.; Sos, M.L. The next tier of EGFR resistance mutations in lung cancer. Oncogene, 2021, 40(1), 1-11.
[http://dx.doi.org/10.1038/s41388-020-01510-w] [PMID: 33060857]
[54]
Sidorov, M.; Dighe, P.; Woo, R.W.L.; Rodriguez-Brotons, A.; Chen, M.; Ice, R.J.; Vaquero, E.; Jian, D.; Desprez, P.Y.; Nosrati, M.; Galvez, L.; Leng, L.; Dickinson, L.; Kashani-Sabet, M.; McAllister, S.D.; Soroceanu, L. Dual targeting of EGFR and MTOR pathways inhibits glioblastoma growth by modulating the tumor microenvironment. Cells, 2023, 12(4), 547.
[http://dx.doi.org/10.3390/cells12040547] [PMID: 36831214]
[55]
Kang, N.; Cao, S.; Jiang, B.; Zhang, Q.; Donkor, P.O.; Zhu, Y.; Qiu, F.; Gao, X. Cetuximab enhances oridonin-induced apoptosis through mitochondrial pathway and endoplasmic reticulum stress in laryngeal squamous cell carcinoma cells. Toxicol. In vitro, 2020, 67, 104885.
[http://dx.doi.org/10.1016/j.tiv.2020.104885] [PMID: 32407876]
[56]
Li, D.; Wu, L.; Tashiro, S.; Onodera, S.; Ikejima, T. Oridonin-induced A431 cell apoptosis partially through blockage of the Ras/Raf/ERK signal pathway. J. Pharmacol. Sci., 2007, 103(1), 56-66.
[http://dx.doi.org/10.1254/jphs.FPJ06016X] [PMID: 17251686]
[57]
Xiao, X.; He, Z.; Cao, W.; Cai, F.; Zhang, L.; Huang, Q.; Fan, C.; Duan, C.; Wang, X.; Wang, J.; Liu, Y. Oridonin inhibits gefitinib-resistant lung cancer cells by suppressing EGFR/ERK/MMP-12 and CIP2A/Akt signaling pathways. Int. J. Oncol., 2016, 48(6), 2608-2618.
[http://dx.doi.org/10.3892/ijo.2016.3488] [PMID: 27082429]
[58]
Pi, J.; Jiang, J.; Cai, H.; Yang, F.; Jin, H.; Yang, P.; Cai, J.; Chen, Z.W. GE11 peptide conjugated selenium nanoparticles for EGFR targeted oridonin delivery to achieve enhanced anticancer efficacy by inhibiting EGFR-mediated PI3K/AKT and Ras/Raf/MEK/ERK pathways. Drug Deliv., 2017, 24(1), 1549-1564.
[http://dx.doi.org/10.1080/10717544.2017.1386729] [PMID: 29019267]
[59]
Verzella, D.; Pescatore, A.; Capece, D.; Vecchiotti, D.; Ursini, M.V.; Franzoso, G.; Alesse, E.; Zazzeroni, F. Life, death, and autophagy in cancer: NF-κB turns up everywhere. Cell Death Dis., 2020, 11(3), 210.
[http://dx.doi.org/10.1038/s41419-020-2399-y] [PMID: 32231206]
[60]
Leung, C.H.; Grill, S.P.; Lam, W.; Han, Q.B.; Sun, H.D.; Cheng, Y.C. Novel mechanism of inhibition of nuclear factor-kappa B DNA-binding activity by diterpenoids isolated from Isodon rubescens. Mol. Pharmacol., 2005, 68(2), 286-297.
[http://dx.doi.org/10.1124/mol.105.012765] [PMID: 15872117]
[61]
Dong, X.; Liu, F.; Li, M. Inhibition of nuclear factor κB transcription activity drives a synergistic effect of cisplatin and oridonin on HepG2 human hepatocellular carcinoma cells. Anticancer Drugs, 2016, 27(4), 286-299.
[http://dx.doi.org/10.1097/CAD.0000000000000329] [PMID: 26704389]
[62]
Xu, X.; Lai, Y.; Hua, Z.C. Apoptosis and apoptotic body: Disease message and therapeutic target potentials. Biosci. Rep., 2019, 39(1), BSR20180992.
[http://dx.doi.org/10.1042/BSR20180992] [PMID: 30530866]
[63]
Bao, R.; Shu, Y.; Wu, X.; Weng, H.; Ding, Q.; Cao, Y.; Li, M.; Mu, J.; Wu, W.; Ding, Q.; Tan, Z.; Liu, T.; Jiang, L.; Hu, Y.; Gu, J.; Liu, Y. Oridonin induces apoptosis and cell cycle arrest of gallbladder cancer cells via the mitochondrial pathway. BMC Cancer, 2014, 14(1), 217.
[http://dx.doi.org/10.1186/1471-2407-14-217] [PMID: 24655726]
[64]
Ikezoe, T.; Yang, Y.; Bandobashi, K.; Saito, T.; Takemoto, S.; Machida, H.; Togitani, K.; Koeffler, H.P.; Taguchi, H. Oridonin, a diterpenoid purified from Rabdosia rubescens, inhibits the proliferation of cells from lymphoid malignancies in association with blockade of the NF-κB signal pathways. Mol. Cancer Ther., 2005, 4(4), 578-586.
[http://dx.doi.org/10.1158/1535-7163.MCT-04-0277] [PMID: 15827331]
[65]
O’Donnell, J.S.; Massi, D.; Teng, M.W.L.; Mandala, M. PI3K-AKT-mTOR inhibition in cancer immunotherapy, redux. Semin. Cancer Biol., 2018, 48, 91-103.
[http://dx.doi.org/10.1016/j.semcancer.2017.04.015] [PMID: 28467889]
[66]
Janku, F.; Yap, T.A.; Meric-Bernstam, F. Targeting the PI3K pathway in cancer: Are we making headway? Nat. Rev. Clin. Oncol., 2018, 15(5), 273-291.
[http://dx.doi.org/10.1038/nrclinonc.2018.28] [PMID: 29508857]
[67]
Donohoe, F.; Wilkinson, M.; Baxter, E.; Brennan, D.J. Mitogen-activated protein kinase (MAPK) and obesity-related cancer. Int. J. Mol. Sci., 2020, 21(4), 1241.
[http://dx.doi.org/10.3390/ijms21041241] [PMID: 32069845]
[68]
Liu, R.X.; Ma, Y.; Hu, X.L.; Ren, W.Y.; Liao, Y.P.; Wang, H.; Zhu, J.H.; Wu, K.; He, B.C.; Sun, W.J. Anticancer effects of oridonin on colon cancer are mediated via BMP7/p38 MAPK/p53 signaling. Int. J. Oncol., 2018, 53(5), 2091-2101.
[http://dx.doi.org/10.3892/ijo.2018.4527] [PMID: 30132514]
[69]
Zhang, C.L.; Wu, L.J.; Tashiro, S.I.; Onodera, S.; Ikejima, T. Oridonin induced A375-S2 cell apoptosis via BAX-regulated caspase pathway activation, dependent on the cytochrome C/CASPASE-9 apoptosome. J. Asian Nat. Prod. Res., 2004, 6(2), 127-138.
[http://dx.doi.org/10.1080/1028602031000147375] [PMID: 15008459]
[70]
Zhang, C.L.; Wu, L.J.; Tashiro, S.; Onodera, S.; Ikejima, T. Oridonin induces a caspase-independent but mitochondria- and MAPK-dependent cell death in the murine fibrosarcoma cell line L929. Biol. Pharm. Bull., 2004, 27(10), 1527-1531.
[http://dx.doi.org/10.1248/bpb.27.1527] [PMID: 15467189]
[71]
Cai, D.; Jin, H.; Xiong, Q.X.; Liu, W.G.; Gao, Z.; Gu, G.; Qiu, Y. ER stress and ASK1-JNK activation contribute to oridonin-induced apoptosis and growth inhibition in cultured human hepatoblastoma HuH-6 cells. Mol. Cell. Biochem., 2013, 379(1-2), 161-169.
[http://dx.doi.org/10.1007/s11010-013-1638-2] [PMID: 23580093]
[72]
Liang, J.; Wang, W.; Wei, L.; Gao, S.; Wang, Y. Oridonin inhibits growth and induces apoptosis of human neurocytoma cells via the Wnt/β-catenin pathway. Oncol. Lett., 2018, 16(3), 3333-3340.
[http://dx.doi.org/10.3892/ol.2018.8977] [PMID: 30127932]
[73]
Xia, S.; Zhang, X.; Li, C.; Guan, H. Oridonin inhibits breast cancer growth and metastasis through blocking the Notch signaling. Saudi Pharm. J., 2017, 25(4), 638-643.
[http://dx.doi.org/10.1016/j.jsps.2017.04.037] [PMID: 28579904]
[74]
Perez-Fidalgo, J.A.; Ortega, B.; Simon, S.; Samartzis, E.P.; Boussios, S. NOTCH signalling in ovarian cancer angiogenesis. Ann. Transl. Med., 2020, 8(24), 1705.
[http://dx.doi.org/10.21037/atm-20-4497] [PMID: 33490217]
[75]
Dong, Y.; Zhang, T.; Li, J.; Deng, H.; Song, Y.; Zhai, D.; Peng, Y.; Lu, X.; Liu, M.; Zhao, Y.; Yi, Z. Oridonin inhibits tumor growth and metastasis through anti-angiogenesis by blocking the notch signaling. PLoS One, 2014, 9(12), e113830.
[http://dx.doi.org/10.1371/journal.pone.0113830] [PMID: 25485753]
[76]
Liu, H.; Qian, C.; Shen, Z. Anti-tumor activity of oridonin on SNU-5 subcutaneous xenograft model via regulation of c-Met pathway. Tumour Biol., 2014, 35(9), 9139-9146.
[http://dx.doi.org/10.1007/s13277-014-2178-4] [PMID: 24916572]
[77]
Liu, Y.; Liu, J.H.; Chai, K.; Tashiro, S.I.; Onodera, S.; Ikejima, T. Inhibition of c-Met promoted apoptosis, autophagy and loss of the mitochondrial transmembrane potential in oridonin-induced A549 lung cancer cells. J. Pharm. Pharmacol., 2013, 65(11), 1622-1642.
[http://dx.doi.org/10.1111/jphp.12140] [PMID: 24102522]
[78]
Duan, D.; Wang, X.; Feng, X.; Pan, D.; Wang, L.; Wang, Y. Oridonin induces oxidative stress-mediated cancer cells apoptosis via targeting thioredoxin reductase. Curr. Pharm. Biotechnol., 2022, 23(14), 1647-1657.
[http://dx.doi.org/10.2174/1389201023666211217151955] [PMID: 34923938]
[79]
Liu, W.; Wang, X.; Wang, L.; Mei, Y.; Yun, Y.; Yao, X.; Chen, Q.; Zhou, J.; Kou, B. Oridonin represses epithelial-mesenchymal transition and angiogenesis of thyroid cancer via downregulating JAK2/STAT3 signaling. Int. J. Med. Sci., 2022, 19(6), 965-974.
[http://dx.doi.org/10.7150/ijms.70733] [PMID: 35813296]
[80]
Cao, Y.; Wei, W.; Zhang, N.; Yu, Q.; Xu, W.B.; Yu, W.J.; Chen, G.Q.; Wu, Y.L.; Yan, H. Oridonin stabilizes retinoic acid receptor alpha through ROS-activated NF-κB signaling. BMC Cancer., 2015, 15(1), 248.
[http://dx.doi.org/10.1186/s12885-015-1219-8] [PMID: 25886043]
[81]
Wang, S.; Zhong, Z.; Wan, J.; Tan, W.; Wu, G.; Chen, M.; Wang, Y. Oridonin induces apoptosis, inhibits migration and invasion on highly-metastatic human breast cancer cells. Am. J. Chin. Med., 2013, 41(1), 177-196.
[http://dx.doi.org/10.1142/S0192415X13500134] [PMID: 23336515]
[82]
Zeng, R.; Chen, Y.; Zhao, S.; Cui, G. Autophagy counteracts apoptosis in human multiple myeloma cells exposed to oridonin in vitrovia regulating intracellular ROS and SIRT1. Acta Pharmacol. Sin., 2012, 33(1), 91-100.
[http://dx.doi.org/10.1038/aps.2011.143] [PMID: 22158107]
[83]
Xu, W.; Sun, J.; Zhang, T.; Ma, B.; Cui, S.; Chen, D.; He, Z. Pharmacokinetic behaviors and oral bioavailability of oridonin in rat plasma. Acta Pharmacol. Sin., 2006, 27(12), 1642-1646.
[http://dx.doi.org/10.1111/j.1745-7254.2006.00440.x] [PMID: 17112421]
[84]
Ding, C.; Zhang, Y.; Chen, H.; Yang, Z.; Wild, C.; Chu, L.; Liu, H.; Shen, Q.; Zhou, J. Novel nitrogen-enriched oridonin analogues with thiazole-fused A-ring: protecting group-free synthesis, enhanced anticancer profile, and improved aqueous solubility. J. Med. Chem., 2013, 56(12), 5048-5058.
[http://dx.doi.org/10.1021/jm400367n] [PMID: 23746196]
[85]
Zhang, Y.; Wang, S.; Dai, M.; Nai, J.; Zhu, L.; Sheng, H. Solubility and bioavailability enhancement of oridonin: A review. Molecules, 2020, 25(2), 332.
[http://dx.doi.org/10.3390/molecules25020332] [PMID: 31947574]
[86]
Xu, S.; Yao, H.; Luo, S.; Zhang, Y.K.; Yang, D.H.; Li, D.; Wang, G.; Hu, M.; Qiu, Y.; Wu, X.; Yao, H.; Xie, W.; Chen, Z.S.; Xu, J. A novel potent anticancer compound optimized from a natural oridonin scaffold induces apoptosis and cell cycle arrest through the mitochondrial pathway. J. Med. Chem., 2017, 60(4), 1449-1468.
[http://dx.doi.org/10.1021/acs.jmedchem.6b01652] [PMID: 28165738]
[87]
Zhou, X.; Zhang, X.; Ye, Y.; Zhang, T.; Wang, H.; Ma, Z.; Wu, B. Nanostructured lipid carriers used for oral delivery of oridonin: An effect of ligand modification on absorption. Int. J. Pharm., 2015, 479(2), 391-398.
[http://dx.doi.org/10.1016/j.ijpharm.2014.12.068] [PMID: 25556104]
[88]
Lin, F.; Zhang, X.; Zhang, Y.; Wang, J. Preparation, characterization, and pharmacokinetics of oridonin-loaded liposomes. Biomed. Chromatogr., 2023, 37(5), e5603.
[http://dx.doi.org/10.1002/bmc.5603] [PMID: 36781382]

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