Targeting RSK2 in Cancer Therapy: A Review of Natural Products


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Abstract

P90 ribosomal S6 kinase 2 (RSK2) is an important member of the RSK family, functioning as a kinase enzyme that targets serine and threonine residues and contributes to regulating cell growth. RSK2 comprises two major functional domains: the N-terminal kinase domain (NTKD) and the C-terminal kinase domain (CTKD). RSK2 is situated at the lower end of the Mitogen-activated protein kinases (MAPK) signaling pathway and is phosphorylated by the direct regulation of Extracellular signal-regulating kinase (ERK). RSK2 has been found to play a pivotal role in regulating cell proliferation, apoptosis, metastasis, and invasion in various cancer cells, including breast cancer and melanoma. Consequently, RSK2 has emerged as a potential target for the development of anti-cancer drugs. Presently, several inhibitors are undergoing clinical trials, such as SL0101. Current inhibitors of RSK2 mainly bind to its NTK or CTK domains and inhibit their activity. Natural products serve as an important resource for drug development and screening and with the potential to identify RSK2 inhibitors. This article discusses how RSK2 influences tumor cell proliferation, prevents apoptosis, arrests the cell cycle process, and promotes cancer metastasis through its regulation of downstream pathways or interaction with other biological molecules. Additionally, the paper also covers recent research progress on RSK2 inhibitors and the mechanisms of action of natural RSK2 inhibitors on tumors. This review emphasizes the significance of RSK2 as a potential therapeutic target in cancer and offers a theoretical basis for the clinical application of RSK2 inhibitors.

About the authors

Tianhui Wu

School of Chemistry and Life Science, Suzhou University of Science and Technology

Email: info@benthamscience.net

Ziming Chen

School of Chemistry and Life Science, Suzhou University of Science and Technology

Email: info@benthamscience.net

Xin Liu

School of Chemistry and Life Science, Suzhou University of Science and Technology

Email: info@benthamscience.net

Xinyan Wu

School of Chemistry and Life Science, Suzhou University of Science and Technology

Email: info@benthamscience.net

Zhaobo Wang

School of Chemistry and Life Science, Suzhou University of Science and Technology

Email: info@benthamscience.net

Weiqiang Guo

School of Chemistry and Life Science, Suzhou University of Science and Technology

Author for correspondence.
Email: info@benthamscience.net

References

  1. Romeo, Y.; Zhang, X.; Roux, P.P. Regulation and function of the RSK family of protein kinases. Biochem. J., 2012, 441(2), 553-569. doi: 10.1042/BJ20110289 PMID: 22187936
  2. Dümmler, B.A.; Hauge, C.; Silber, J.; Yntema, H.G.; Kruse, L.S.; Kofoed, B.; Hemmings, B.A.; Alessi, D.R.; Frödin, M. Functional characterization of human RSK4, a new 90-kDa ribosomal S6 kinase, reveals constitutive activation in most cell types. J. Biol. Chem., 2005, 280(14), 13304-13314. doi: 10.1074/jbc.M408194200 PMID: 15632195
  3. Eisinger-Mathason, T.S.K.; Andrade, J.; Lannigan, D.A. RSK in tumorigenesis: Connections to steroid signaling. Steroids, 2010, 75(3), 191-202. doi: 10.1016/j.steroids.2009.12.010 PMID: 20045011
  4. Jones, S.W.; Erikson, E.; Blenis, J.; Maller, J.L.; Erikson, R.L. A Xenopus ribosomal protein S6 kinase has two apparent kinase domains that are each similar to distinct protein kinases. Proc. Natl. Acad. Sci. USA, 1988, 85(10), 3377-3381. doi: 10.1073/pnas.85.10.3377 PMID: 3368449
  5. Fisher, T.L.; Blenis, J. Evidence for two catalytically active kinase domains in pp90rsk. Mol. Cell. Biol., 1996, 16(3), 1212-1219. doi: 10.1128/MCB.16.3.1212 PMID: 8622665
  6. Arul, N.; Cho, Y.Y. A Rising Cancer Prevention Target of RSK2 in Human Skin Cancer. Front. Oncol., 2013, 3, 201. doi: 10.3389/fonc.2013.00201 PMID: 23936765
  7. Cho, Y.Y. RSK2 and its binding partners in cell proliferation, transformation and cancer development. Arch. Pharm. Res., 2017, 40(3), 291-303. doi: 10.1007/s12272-016-0880-z PMID: 28013489
  8. Choi, J.S.; Cho, Y.Y. Novel wiring of the AKT-RSK2 signaling pathway plays an essential role in cancer cell proliferation via a G1/S cell cycle transition. Biochem. Biophys. Res. Commun., 2023, 642, 66-74. doi: 10.1016/j.bbrc.2022.12.048 PMID: 36566564
  9. Guo, Z.F.; Kong, F.L. Akt regulates RSK2 to alter phosphorylation level of H2A.X in breast cancer. Oncol. Lett., 2021, 21(3), 187. doi: 10.3892/ol.2021.12448 PMID: 33574926
  10. Wang, L.; Iorio, C.; Yan, K.; Yang, H.; Takeshita, S.; Kang, S.; Neel, B.G.; Yang, W. A ERK/RSK‐mediated negative feedback loop regulates M‐CSF–evoked PI3K/AKT activation in macrophages. FASEB J., 2018, 32(2), 875-887. doi: 10.1096/fj.201700672RR PMID: 29046360
  11. Kuppusamy, P.; Nagalingam, A.; Muniraj, N.; Saxena, N.K.; Sharma, D. Concomitant activation of ETS-like transcription factor-1 and Death Receptor-5 via extracellular signal-regulated kinase in withaferin A-mediated inhibition of hepatocarcinogenesis in mice. Sci. Rep., 2017, 7(1), 17943. doi: 10.1038/s41598-017-18190-4 PMID: 29263422
  12. Yoo, S.M.; Lee, C.J.; An, H.J.; Lee, J.Y.; Lee, H.S.; Kang, H.C.; Cho, S.J.; Kim, S.M.; Park, J.; Kim, D.J.; Cho, Y.Y. RSK2-mediated ELK3 activation enhances cell transformation and breast cancer cell growth by regulation of c-fos promoter activity. Int. J. Mol. Sci., 2019, 20(8), 1994. doi: 10.3390/ijms20081994 PMID: 31018569
  13. Abdulrahman, N.; Siveen, K.S.; Joseph, J.M.; Osman, A.; Yalcin, H.C.; Hasan, A.; Uddin, S.; Mraiche, F. Inhibition of p90 ribosomal S6 kinase potentiates cisplatin activity in A549 human lung adenocarcinoma cells. J. Pharm. Pharmacol., 2020, 72(11), 1536-1545. doi: 10.1111/jphp.13335 PMID: 32667058
  14. Zheng, K.; Yao, S.; Yao, W.; Li, Q.; Wang, Y.; Zhang, L.; Chen, X.; Xiong, H.; Yuan, X.; Wang, Y.; Zou, Y.; Xiong, H. Association between RSK2 and clinical indexes of primary breast cancer: A meta-analysis based on mRNA microarray data. Front. Genet., 2021, 12, 770134. doi: 10.3389/fgene.2021.770134 PMID: 34790230
  15. Czaplinska, D.; Mieczkowski, K.; Supernat, A.; Skladanowski, A.C.; Kordek, R.; Biernat, W.; Zaczek, A.J.; Romanska, H.M.; Sadej, R. Interactions between FGFR2 and RSK2—implications for breast cancer prognosis. Tumour Biol., 2016, 37(10), 13721-13731. doi: 10.1007/s13277-016-5266-9 PMID: 27476168
  16. Li, J.J.; Rhim, J.S.; Schlegel, R.; Vousden, K.H.; Colburn, N.H. Expression of dominant negative Jun inhibits elevated AP-1 and NF-κB transactivation and suppresses anchorage independent growth of HPV immortalized human keratinocytes. Oncogene, 1998, 16(21), 2711-2721. doi: 10.1038/sj.onc.1201798 PMID: 9652737
  17. Zhang, X.; Guo, Y.; Xiao, T.; Li, J.; Guo, A.; Lei, L.; Jin, C.; Long, Q.; Su, J.; Yin, M.; Liu, H.; Chen, C.; Zhou, Z.; Zhu, S.; Tao, J.; Hu, S.; Chen, X.; Peng, C. CD147 mediates epidermal malignant transformation through the RSK2/AP-1 pathway. J. Exp. Clin. Cancer Res., 2022, 41(1), 246. doi: 10.1186/s13046-022-02427-w PMID: 35964097
  18. Jiang, D.; Qiu, T.; Peng, J.; Li, S.; Tala; Ren, W.; Yang, C.; Wen, Y.; Chen, C.H.; Sun, J.; Wu, Y.; Liu, R.; Zhou, J.; Wu, K.; Liu, W.; Mao, X.; Zhou, Z.; Chen, C. YB-1 is a positive regulator of KLF5 transcription factor in basal-like breast cancer. Cell Death Differ., 2022, 29(6), 1283-1295. doi: 10.1038/s41418-021-00920-x PMID: 35022570
  19. Stratford, A.L.; Fry, C.J.; Desilets, C.; Davies, A.H.; Cho, Y.Y.; Li, Y.; Dong, Z.; Berquin, I.M.; Roux, P.P.; Dunn, S.E. Y-box binding protein-1 serine 102 is a downstream target of p90 ribosomal S6 kinase in basal-like breast cancer cells. Breast Cancer Res., 2008, 10(6), R99. doi: 10.1186/bcr2202 PMID: 19036157
  20. She, Q.B.; Ma, W.Y.; Zhong, S.; Dong, Z. Activation of JNK1, RSK2, and MSK1 is involved in serine 112 phosphorylation of Bad by ultraviolet B radiation. J. Biol. Chem., 2002, 277(27), 24039-24048. doi: 10.1074/jbc.M109907200 PMID: 11983683
  21. Peng, C.; Cho, Y.Y.; Zhu, F.; Li, H.; Li, X.; Xie, H.; Bode, A.M.; Dong, Z. Abstract 4968: Phosphorylation of caspase-8 (Thr263) by ribosomal S6 kinase 2 (RSK2) mediates caspase-8 ubiquitination and stability. Cancer Res., 2012, 72(8_Supplement)(Suppl.), 4968-4968. doi: 10.1158/1538-7445.AM2012-4968
  22. Lee, C.J.; Lee, M.H.; Lee, J.Y.; Song, J.H.; Lee, H.S.; Cho, Y.Y. RSK2-induced stress tolerance enhances cell survival signals mediated by inhibition of GSK3β activity. Biochem. Biophys. Res. Commun., 2013, 440(1), 112-118. doi: 10.1016/j.bbrc.2013.09.042 PMID: 24055036
  23. He, Z.; Ma, W.Y.; Liu, G.; Zhang, Y.; Bode, A.M.; Dong, Z. Arsenite-induced phosphorylation of histone H3 at serine 10 is mediated by Akt1, extracellular signal-regulated kinase 2, and p90 ribosomal S6 kinase 2 but not mitogen- and stress-activated protein kinase 1. J. Biol. Chem., 2003, 278(12), 10588-10593. doi: 10.1074/jbc.M208581200 PMID: 12529330
  24. Cho, Y.Y.; He, Z.; Zhang, Y.; Choi, H.S.; Zhu, F.; Choi, B.Y.; Kang, B.S.; Ma, W.Y.; Bode, A.M.; Dong, Z. The p53 protein is a novel substrate of ribosomal S6 kinase 2 and a critical intermediary for ribosomal S6 kinase 2 and histone H3 interaction. Cancer Res., 2005, 65(9), 3596-3603. doi: 10.1158/0008-5472.CAN-04-3935 PMID: 15867353
  25. Lau, A.T.Y.; Lee, S.Y.; Xu, Y.M.; Zheng, D.; Cho, Y.Y.; Zhu, F.; Kim, H.G.; Li, S.Q.; Zhang, Z.; Bode, A.M.; Dong, Z. Phosphorylation of histone H2B serine 32 is linked to cell transformation. J. Biol. Chem., 2011, 286(30), 26628-26637. doi: 10.1074/jbc.M110.215590 PMID: 21646345
  26. Zhu, F.; Zykova, T.A.; Peng, C.; Zhang, J.; Cho, Y.Y.; Zheng, D.; Yao, K.; Ma, W.Y.; Lau, A.T.Y.; Bode, A.M.; Dong, Z. Phosphorylation of H2AX at Ser139 and a new phosphorylation site Ser16 by RSK2 decreases H2AX ubiquitination and inhibits cell transformation. Cancer Res., 2011, 71(2), 393-403. doi: 10.1158/0008-5472.CAN-10-2012 PMID: 21224359
  27. Penzo, C.; Arnoldo, L.; Pegoraro, S.; Petrosino, S.; Ros, G.; Zanin, R.; Wiśniewski, J.R.; Manfioletti, G.; Sgarra, R. HMGA1 modulates gene transcription sustaining a tumor signalling pathway acting on the epigenetic status of triple-negative breast cancer cells. Cancers (Basel), 2019, 11(8), 1105. doi: 10.3390/cancers11081105 PMID: 31382504
  28. Liu, K.; Cho, Y.Y.; Yao, K.; Nadas, J.; Kim, D.J.; Cho, E.J.; Lee, M.H.; Pugliese, A.; Zhang, J.; Bode, A.M.; Dong, Z.; Dong, Z. Eriodictyol inhibits RSK2-ATF1 signaling and suppresses EGF-induced neoplastic cell transformation. J. Biol. Chem., 2011, 286(3), 2057-2066. doi: 10.1074/jbc.M110.147306 PMID: 21098035
  29. Kang, J.; Chun, J.; Hwang, J.S.; Pan, C.; Li, J.; Boese, A.C.; Young, I.; Malin, C.M.; Kang, Y.; Gibbons, D.L.; Sica, G.; Fu, H.; Ramalingam, S.S.; Jin, L.; Kang, S. EGFR-phosphorylated GDH1 harmonizes with RSK2 to drive CREB activation and tumor metastasis in EGFR-activated lung cancer. Cell Rep., 2022, 41(11), 111827. doi: 10.1016/j.celrep.2022.111827 PMID: 36516759
  30. Vanden Berghe, W.; De Naeyer, A.; Dijsselbloem, N.; David, J.P.; De Keukeleire, D.; Haegeman, G. Attenuation of ERK/RSK2-driven NFκB gene expression and cancer cell proliferation by kurarinone, a lavandulyl flavanone isolated from Sophora flavescens ait. roots. Endocr. Metab. Immune Disord. Drug Targets, 2011, 11(3), 247-261. doi: 10.2174/187153011796429790 PMID: 21831037
  31. Qian, X.; Xu, Q.; Li, G.; Bu, Y.; Sun, F.; Zhang, J. Therapeutic effect of idebenone on rats with vascular dementia via the MicroRNA-216a/RSK2/NF-κB axis. Neuropsychiatr. Dis. Treat., 2021, 17, 533-543. doi: 10.2147/NDT.S293614 PMID: 33628024
  32. Wu, H.Z.; Li, L.Y.; Jiang, S.L.; Li, Y.Z.; Shi, X.M.; Sun, X.Y.; Li, Z.; Cheng, Y. RSK2 promotes melanoma cell proliferation and vemurafenib resistance via upregulating cyclin D1. Front. Pharmacol., 2022, 13, 950571. doi: 10.3389/fphar.2022.950571 PMID: 36210843
  33. Kosnopfel, C.; Sinnberg, T.; Sauer, B.; Niessner, H.; Schmitt, A.; Makino, E.; Forschner, A.; Hailfinger, S.; Garbe, C.; Schittek, B. Human melanoma cells resistant to MAPK inhibitors can be effectively targeted by inhibition of the p90 ribosomal S6 kinase. Oncotarget, 2017, 8(22), 35761-35775. doi: 10.18632/oncotarget.16204 PMID: 28415756
  34. Li, Y.; Yu, P.; Long, J.; Tang, L.; Zhang, X.; Zhou, Z.; Cao, D.; Su, J.; Chen, X.; Peng, C. A novel ribosomal protein S6 kinase 2 inhibitor attenuates the malignant phenotype of cutaneous malignant melanoma cells by inducing cell cycle arrest and apoptosis. Bioengineered, 2022, 13(5), 13555-13570. doi: 10.1080/21655979.2022.2080364 PMID: 36700473
  35. Lommel, M.J.; Trairatphisan, P.; Gäbler, K.; Laurini, C.; Muller, A.; Kaoma, T.; Vallar, L.; Sauter, T.; Schaffner-Reckinger, E. L‐plastin Ser5 phosphorylation in breast cancer cells and in vitro is mediated by RSK downstream of the ERK/MAPK pathway. FASEB J., 2016, 30(3), 1218-1233. doi: 10.1096/fj.15-276311 PMID: 26631483
  36. Czaplinska, D.; Turczyk, L.; Grudowska, A.; Mieszkowska, M.; Lipinska, A.D.; Skladanowski, A.C.; Zaczek, A.J.; Romanska, H.M.; Sadej, R. Phosphorylation of RSK2 at Tyr529 by FGFR2-p38 enhances human mammary epithelial cells migration. Biochim. Biophys. Acta Mol. Cell Res., 2014, 1843(11), 2461-2470. doi: 10.1016/j.bbamcr.2014.06.022 PMID: 25014166
  37. Alesi, G.N.; Jin, L.; Li, D.; Magliocca, K.R.; Kang, Y.; Chen, Z.G.; Shin, D.M.; Khuri, F.R.; Kang, S. RSK2 signals through stathmin to promote microtubule dynamics and tumor metastasis. Oncogene, 2016, 35(41), 5412-5421. doi: 10.1038/onc.2016.79 PMID: 27041561
  38. Ma, Q.; Guin, S.; Padhye, S.S.; Zhou, Y.Q.; Zhang, R.W.; Wang, M.H. Ribosomal Protein S6 Kinase (RSK)-2 as a central effector molecule in RON receptor tyrosine kinase mediated epithelial to mesenchymal transition induced by macrophage-stimulating protein. Mol. Cancer, 2011, 10(1), 66. doi: 10.1186/1476-4598-10-66 PMID: 21619683
  39. Mao, L.; Summers, W.; Xiang, S.; Yuan, L.; Dauchy, R.T.; Reynolds, A.; Wren-Dail, M.A.; Pointer, D.; Frasch, T.; Blask, D.E.; Hill, S.M. Melatonin represses metastasis in Her2 -postive human breast cancer cells by suppressing RSK2 expression. Mol. Cancer Res., 2016, 14(11), 1159-1169. doi: 10.1158/1541-7786.MCR-16-0158 PMID: 27535706
  40. Pambid, M.R.; Berns, R.; Adomat, H.H.; Hu, K.; Triscott, J.; Maurer, N.; Zisman, N.; Ramaswamy, V.; Hawkins, C.E.; Taylor, M.D.; Dunham, C.; Guns, E.; Dunn, S.E. Overcoming resistance to sonic hedgehog inhibition by targeting p90 ribosomal S6 kinase in pediatric medulloblastoma. Pediatr. Blood Cancer, 2014, 61(1), 107-115. doi: 10.1002/pbc.24675 PMID: 23940083
  41. Stratford, A.L.; Reipas, K.; Hu, K.; Fotovati, A.; Brough, R.; Frankum, J.; Takhar, M.; Watson, P.; Ashworth, A.; Lord, C.J.; Lasham, A.; Print, C.G.; Dunn, S.E. Targeting p90 ribosomal S6 kinase eliminates tumor-initiating cells by inactivating Y-box binding protein-1 in triple-negative breast cancers. Stem Cells, 2012, 30(7), 1338-1348. doi: 10.1002/stem.1128 PMID: 22674792
  42. Mrozowski, R.M.; Vemula, R.; Wu, B.; Zhang, Q.; Schroeder, B.R.; Hilinski, M.K.; Clark, D.E.; Hecht, S.M.; O’Doherty, G.A.; Lannigan, D.A. Improving the affinity of SL0101 for RSK using structure-based design. ACS Med. Chem. Lett., 2013, 4(2), 175-179. doi: 10.1021/ml300298v PMID: 23519677
  43. Wright, E.B.; Fukuda, S.; Li, M.; Li, Y.; O’Doherty, G.A.; Lannigan, D.A. Identifying requirements for RSK2 specific inhibitors. J. Enzyme Inhib. Med. Chem., 2021, 36(1), 1798-1809. doi: 10.1080/14756366.2021.1957862 PMID: 34348556
  44. Casalvieri, K.A.; Matheson, C.J.; Backos, D.S.; Reigan, P. Substituted pteridinones as p90 ribosomal S6 protein kinase (RSK) inhibitors: A structure-activity study. Bioorg. Med. Chem., 2020, 28(5), 115303. doi: 10.1016/j.bmc.2019.115303 PMID: 31982240
  45. Vicier, C.; Sfumato, P.; Isambert, N.; Dalenc, F.; Robert, M.; Levy, C.; Rezai, K.; Provansal, M. TAKTIC: A prospective, multicentre, uncontrolled, phase IB/II study of LY2780301, a p70S6K/AKT inhibitor, in combination with weekly paclitaxel in HER2-negative advanced breast cancer patients. Euro. J. Cancer, 2021, 159, 205-214.
  46. Ushijima, M.; Shiota, M.; Matsumoto, T.; Kashiwagi, E.; Inokuchi, J.; Eto, M. An oral first‐in‐class small molecule RSK inhibitor suppresses AR variants and tumor growth in prostate cancer. Cancer Sci., 2022, 113(5), 1731-1738. doi: 10.1111/cas.15280 PMID: 35118769
  47. Kosnopfel, C.; Wendlinger, S.; Niessner, H.; Siewert, J.; Sinnberg, T.; Hofmann, A.; Wohlfarth, J.; Schrama, D.; Berthold, M.; Siedel, C.; Sauer, B.; Jayanthan, A.; Lenz, G.; Dunn, S.E.; Schilling, B.; Schittek, B. Inhibition of p90 ribosomal S6 kinases disrupts melanoma cell growth and immune evasion. J. Exp. Clin. Cancer Res., 2023, 42(1), 175. doi: 10.1186/s13046-023-02755-5 PMID: 37464364
  48. Cohen, M.S.; Hadjivassiliou, H.; Taunton, J. A clickable inhibitor reveals context-dependent autoactivation of p90 RSK. Nat. Chem. Biol., 2007, 3(3), 156-160. doi: 10.1038/nchembio859 PMID: 17259979
  49. Cragg, G.M.; Pezzuto, J.M. Natural products as a vital source for the discovery of cancer chemotherapeutic and chemopreventive agents. Med. Princ. Pract., 2016, 25(S2), 41-59. doi: 10.1159/000443404
  50. Mushtaq, S.; Abbasi, B.H.; Uzair, B.; Abbasi, R. Natural products as reservoirs of novel therapeutic agents. EXCLI J., 2018, 17, 420-451. PMID: 29805348
  51. Dias, D.A.; Urban, S.; Roessner, U. A historical overview of natural products in drug discovery. Metabolites, 2012, 2(2), 303-336. doi: 10.3390/metabo2020303 PMID: 24957513
  52. Song, B.; Shen, X.; Tong, C.; Zhang, S.; Chen, Q.; Li, Y.; Li, S. Gossypin: A flavonoid with diverse pharmacological effects. Chem. Biol. Drug Des., 2023, 101(1), 131-137. doi: 10.1111/cbdd.14152 PMID: 36198093
  53. Wang, L.; Wang, X.; Chen, H.; Zu, X.; Ma, F.; Liu, K.; Bode, A.M.; Dong, Z.; Kim, D.J. Gossypin inhibits gastric cancer growth by direct targeting of AURKA and RSK2. Phytother. Res., 2019, 33(3), 640-650. doi: 10.1002/ptr.6253 PMID: 30536456
  54. Cinar, I. Apoptosis-inducing activity and antiproliferative effect of gossypin on PC-3 prostate cancer cells. Anticancer. Agents Med. Chem., 2021, 21(4), 445-450. doi: 10.2174/1871520620666200721103422 PMID: 32698736
  55. Shi, L.; Chen, J.; Wang, Y.; Sun, G.; Liu, J.; Zhang, J.; Yan, W.; Qian, C.; Liu, N.; Fu, Z.; You, Y.; Zeng, Y. Gossypin induces G2/M arrest in human malignant glioma U251 cells by the activation of Chk1/Cdc25C pathway. Cell. Mol. Neurobiol., 2012, 32(2), 289-296. doi: 10.1007/s10571-011-9760-8 PMID: 21984341
  56. Feng, J.; Chen, X.; Wang, Y.; Du, Y.; Sun, Q.; Zang, W.; Zhao, G. Myricetin inhibits proliferation and induces apoptosis and cell cycle arrest in gastric cancer cells. Mol. Cell. Biochem., 2015, 408(1-2), 163-170. doi: 10.1007/s11010-015-2492-1 PMID: 26112905
  57. Reipas, K.M.; Law, J.H.; Couto, N.; Islam, S.; Li, Y.; Li, H.; Cherkasov, A.; Jung, K.; Cheema, A.S.; Jones, S.J.M.; Hassell, J.A.; Dunn, S.E. Luteolin is a novel p90 ribosomal S6 kinase (RSK) inhibitor that suppresses Notch4 signaling by blocking the activation of Y-box binding protein-1 (YB-1). Oncotarget, 2013, 4(2), 329-345. doi: 10.18632/oncotarget.834 PMID: 23593654
  58. Ramasamy, K.; Dwyer-Nield, L.D.; Serkova, N.J.; Hasebroock, K.M.; Tyagi, A.; Raina, K.; Singh, R.P.; Malkinson, A.M.; Agarwal, R. Silibinin prevents lung tumorigenesis in wild-type but not in iNOS-/- mice: potential of real-time micro-CT in lung cancer chemoprevention studies. Clin. Cancer Res., 2011, 17(4), 753-761. doi: 10.1158/1078-0432.CCR-10-2290 PMID: 21148748
  59. Zeng, J.; Sun, Y.; Wu, K.; Li, L.; Zhang, G.; Yang, Z.; Wang, Z.; Zhang, D.; Xue, Y.; Chen, Y.; Zhu, G.; Wang, X.; He, D. Chemopreventive and chemotherapeutic effects of intravesical silibinin against bladder cancer by acting on mitochondria. Mol. Cancer Ther., 2011, 10(1), 104-116. doi: 10.1158/1535-7163.MCT-10-0577 PMID: 21220495
  60. Lee, M.H.; Huang, Z.; Kim, D.J.; Kim, S.H.; Kim, M.O.; Lee, S.Y.; Xie, H.; Park, S.J.; Kim, J.Y.; Kundu, J.K.; Bode, A.M.; Surh, Y.J.; Dong, Z. Direct targeting of MEK1/2 and RSK2 by silybin induces cell-cycle arrest and inhibits melanoma cell growth. Cancer Prev. Res., 2013, 6(5), 455-465. doi: 10.1158/1940-6207.CAPR-12-0425 PMID: 23447564
  61. Kim, J.E.; Heo, Y.S.; Lee, K.W. Osajin inhibits solar UV‐induced cyclooxygenase‐2 expression through direct inhibition of RSK2. J. Cell. Biochem., 2017, 118(11), 4080-4087. doi: 10.1002/jcb.26063 PMID: 28409880
  62. Yao, K.; Chen, H.; Liu, K.; Langfald, A.; Yang, G.; Zhang, Y.; Yu, D.H.; Kim, M.O.; Lee, M.H.; Li, H.; Bae, K.B.; Kim, H.G.; Ma, W.Y.; Bode, A.M.; Dong, Z.; Dong, Z. Kaempferol targets RSK2 and MSK1 to suppress UV radiation-induced skin cancer. Cancer Prev. Res. (Phila.), 2014, 7(9), 958-967. doi: 10.1158/1940-6207.CAPR-14-0126 PMID: 24994661
  63. Wang, L.; Zhang, Y.; Liu, K.; Chen, H.; Yang, R.; Ma, X.; Kim, H.G.; Bode, A.M.; Kim, D.J.; Dong, Z. Carnosol suppresses patient-derived gastric tumor growth by targeting RSK2. Oncotarget, 2018, 9(76), 34200-34212. doi: 10.18632/oncotarget.24409 PMID: 30344937
  64. Chen, H.; Yao, K.; Chang, X.; Shim, J.H.; Kim, H.G.; Malakhova, M.; Kim, D.J.; Bode, A.M.; Dong, Z. Computational and biochemical discovery of rsk2 as a novel target for epigallocatechin gallate (EGCG). PLoS One, 2015, 10(6), e0130049. doi: 10.1371/journal.pone.0130049 PMID: 26083344

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