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Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Research Article

Tanshinone IIA Alleviates the Biological Characteristics of Colorectal Cancer via Activating the ROS/JNK Signaling Pathway

Author(s): Jun Qian, Yi Cao, Junfeng Zhang, Lingchang Li, Juan Wu, Jialin Yu and Jiege Huo*

Volume 23, Issue 2, 2023

Published on: 26 August, 2022

Page: [227 - 236] Pages: 10

DOI: 10.2174/1871520622666220421093430

Price: $65

Abstract

Background: Tanshinone IIA (Tan IIA) exerts a significant inhibitory effect on various tumor cells since it induces cell apoptosis and affects the proliferation, differentiation, metastasis, and invasion of tumor cells. However, the mechanism underlying the antitumor activity of Tan IIA has not been totally elucidated.

Objective: This study aimed to uncover the role of Tan IIA in colorectal cancer (CRC) and its potential mechanism of action.

Methods: Cell proliferation was assessed using CCK-8 and colony formation assays. Western blot analysis was carried out to detect the expression of related proteins. Cell apoptosis was assessed using flow cytometry. Furthermore, tumor size and tumor weight of CRC xenograft mice were recorded before and after Tan IIA treatment. The production of reactive oxygen species (ROS) was measured by a ROS kit.

Results: The results revealed that Tan IIA induced autophagy and apoptosis via activating the ROS/JNK signaling pathway in CRC cells, thus inhibiting the progression of CRC in vivo.

Conclusion: The aforementioned findings indicated that Tan IIA exerted an antiproliferative effect on CRC by inducing cell autophagy and apoptosis via activating the ROS/JNK signaling pathway. Therefore, Tan IIA may be considered a potential therapeutic agent for treating CRC.

Keywords: Tanshinone IIA, colorectal cancer, ROS/JNK signaling pathway, autophagy, apoptosis, antiproliferative.

[1]
Maltseva, D.; Raygorodskaya, M.; Knyazev, E.; Zgoda, V.; Tikhonova, O.; Zaidi, S.; Nikulin, S.; Baranova, A.; Turchi-novich, A.; Rodin, S.; Tonevitsky, A. Knockdown of the α5 laminin chain affects differentiation of colorectal cancer cells and their sensitivity to chemotherapy. Biochimie, 2020, 174, 107-116.
[http://dx.doi.org/10.1016/j.biochi.2020.04.016] [PMID: 32334043]
[2]
Kiczmer, P. Seń;kowska, A.P.; Kula, A.; Dawidowicz, M.; Strzelczyk, J.K.; Zajdel, E.N.; Walkiewicz, K.; Waniczek, D.; Ostrowska, Z.; Świętochowska, E. Assessment of CMKLR1 level in colorectal cancer and its correlation with angiogenic markers. Exp. Mol. Pathol., 2020, 113, 104377.
[http://dx.doi.org/10.1016/j.yexmp.2020.104377] [PMID: 31926977]
[3]
Shike, M.; Winawer, S.J.; Greenwald, P.H.; Bloch, A.; Hill, M.J.; Swaroop, S.V. The WHO collaborating centre for the prevention of colorectal cancer. Primary prevention of colo-rectal cancer. Bull. World Health Organ., 1990, 68(3), 377-385.
[PMID: 2203551]
[4]
Motawi, T.K.; El-Maraghy, S.A.; ElMeshad, A.N.; Nady, O.M.; Hammam, O.A. Cromolyn chitosan nanoparticles as a novel protective approach for colorectal cancer. Chem. Biol. Interact., 2017, 275, 1-12.
[http://dx.doi.org/10.1016/j.cbi.2017.07.013] [PMID: 28732690]
[5]
Liu, N.; Wu, C.; Jia, R.; Cai, G.; Wang, Y.; Zhou, L.; Ji, Q.; Sui, H.; Zeng, P.; Xiao, H.; Liu, H.; Huo, J.; Feng, Y.; Deng, W.; Li, Q. Traditional chinese medicine combined with chem-otherapy and cetuximab or bevacizumab for metastatic colo-rectal cancer: A randomized, double-blind, placebo-controlled clinical trial. Front. Pharmacol., 2020, 11, 478.
[http://dx.doi.org/10.3389/fphar.2020.00478] [PMID: 32372960]
[6]
Wang, Z.; Chen, T.; Yang, C.; Bao, T.; Yang, X.; He, F.; Zhang, Y.; Zhu, L.; Chen, H.; Rong, S.; Yang, S. Secoisolar-iciresinol diglucoside suppresses dextran sulfate sodium salt-induced colitis through inhibiting NLRP1 inflammasome. Int. Immunopharmacol., 2020, 78, 105931.
[http://dx.doi.org/10.1016/j.intimp.2019.105931] [PMID: 31812068]
[7]
Wang, Y.; Liu, P.; Fang, Y.; Tian, J.; Li, S.; Xu, J.; Zhao, F.; Yin, X.; Zhang, Q.; Li, Y. The effect of long-term traditional chinese medicine treatment on survival time of colorectal can-cer based on propensity score matching: A retrospective co-hort study. Evid. Based Complement. Alternat. Med., 2020, 2020, 7023420.
[http://dx.doi.org/10.1155/2020/7023420] [PMID: 32089727]
[8]
Wang, X.; Yang, Y.; Liu, X.; Gao, X. Pharmacological proper-ties of tanshinones, the natural products from Salvia miltior-rhiza. Adv. Pharmacol., 2020, 87, 43-70.
[http://dx.doi.org/10.1016/bs.apha.2019.10.001] [PMID: 32089238]
[9]
Zhao, X.; Yang, D.H.; Xu, F.; Huang, S.; Zhang, L.; Liu, G.X.; Cai, S.Q. The in vivo absorbed constituents and metabolites of danshen decoction in rats identified by HPLC with elec-trospray ionization tandem ion trap and time-of-flight mass spectrometry. Biomed. Chromatogr., 2015, 29(2), 285-304.
[http://dx.doi.org/10.1002/bmc.3275] [PMID: 24995595]
[10]
Wang, R.; Zhang, H.; Wang, Y.; Yu, X.; Yuan, Y. Effects of salvianolic acid B and tanshinone IIA on the pharmacokinet-ics of losartan in rats by regulating the activities and expres-sion of CYP3A4 and CYP2C9. J. Ethnopharmacol., 2016, 180, 87-96.
[http://dx.doi.org/10.1016/j.jep.2016.01.021] [PMID: 26806573]
[11]
Zhang, Y.; Wei, R.X.; Zhu, X.B.; Cai, L.; Jin, W.; Hu, H. Tanshinone IIA induces apoptosis and inhibits the prolifera-tion, migration, and invasion of the osteosarcoma MG-63 cell line in vitro. Anticancer Drugs, 2012, 23(2), 212-219.
[http://dx.doi.org/10.1097/CAD.0b013e32834e5592] [PMID: 22126901]
[12]
He, L.; Gu, K. Tanshinone IIA regulates colorectal cancer apoptosis via attenuation of Parkin mediated mitophagy by suppressing AMPK/Skp2 pathways. Mol. Med. Rep., 2018, 18(2), 1692-1703.
[http://dx.doi.org/10.3892/mmr.2018.9087] [PMID: 29845197]
[13]
Qiu, Y.; Li, C.; Wang, Q.; Zeng, X.; Ji, P. Tanshinone IIA induces cell death via Beclin-1-dependent autophagy in oral squamous cell carcinoma SCC-9 cell line. Cancer Med., 2018, 7(2), 397-407.
[http://dx.doi.org/10.1002/cam4.1281] [PMID: 29316373]
[14]
Chang, C.C.; Kuan, C.P.; Lin, J.Y.; Lai, J.S.; Ho, T.F. Tanshinone IIA facilitates trail sensitization by Up-regulating DR5 through the ROS-JNK-CHOP signaling axis in human ovarian carcinoma cell lines. Chem. Res. Toxicol., 2015, 28(8), 1574-1583.
[http://dx.doi.org/10.1021/acs.chemrestox.5b00150] [PMID: 26203587]
[15]
Li, B.; Zhou, P.; Xu, K.; Chen, T.; Jiao, J.; Wei, H.; Yang, X.; Xu, W.; Wan, W.; Xiao, J. Metformin induces cell cycle arrest, apoptosis and autophagy through ROS/JNK signaling pathway in human osteosarcoma. Int. J. Biol. Sci., 2020, 16(1), 74-84.
[http://dx.doi.org/10.7150/ijbs.33787] [PMID: 31892847]
[16]
Yuan, X.; Jing, S.; Wu, L.; Chen, L.; Fang, J. Pharmacological postconditioning with tanshinone IIA attenuates myocardial ischemia-reperfusion injury in rats by activating the phospha-tidylinositol 3-kinase pathway. Exp. Ther. Med., 2014, 8(3), 973-977.
[http://dx.doi.org/10.3892/etm.2014.1820] [PMID: 25120632]
[17]
Zhuo, F.F.; Zhang, C.; Zhang, H.; Xia, Y.; Xue, G.M.; Yang, L.; Kong, L.Y. Chrysanthemulide A induces apoptosis through DR5 upregulation via JNK-mediated autophagosome accumulation in human osteosarcoma cells. J. Cell. Physiol., 2019, 234(8), 13191-13208.
[http://dx.doi.org/10.1002/jcp.27991] [PMID: 30556589]
[18]
Yuan, L.; Li, Q.; Zhang, Z.; Liu, Q.; Wang, X.; Fan, L. Tanshinone IIA inhibits the adipogenesis and inflammatory response in ox-LDL-challenged human monocyte-derived macrophages via regulating miR-130b/WNT5A. J. Cell. Biochem., 2020, 121(2), 1400-1408.
[http://dx.doi.org/10.1002/jcb.29375] [PMID: 31512787]
[19]
Tsai, M.Y.; Yang, R.C.; Wu, H.T.; Pang, J.H.; Huang, S.T. Anti-angiogenic effect of Tanshinone IIA involves inhibition of matrix invasion and modification of MMP-2/TIMP-2 se-cretion in vascular endothelial cells. Cancer Lett., 2011, 310(2), 198-206.
[http://dx.doi.org/10.1016/j.canlet.2011.06.031] [PMID: 21788102]
[20]
Yuxian, X.; Feng, T.; Ren, L.; Zhengcai, L. Tanshinone II-A inhibits invasion and metastasis of human hepatocellular car-cinoma cells in vitro and in vivo. Tumori, 2009, 95(6), 789-795.
[http://dx.doi.org/10.1177/030089160909500623] [PMID: 20210245]
[21]
Shan, Y.F.; Shen, X.; Xie, Y.K.; Chen, J.C.; Shi, H.Q.; Yu, Z.P.; Song, Q.T.; Zhou, M.T.; Zhang, Q.Y. Inhibitory effects of tanshinone II-A on invasion and metastasis of human co-lon carcinoma cells. Acta Pharmacol. Sin., 2009, 30(11), 1537-1542.
[http://dx.doi.org/10.1038/aps.2009.139] [PMID: 19820721]
[22]
Wang, J.; Hu, R.; Yin, C.; Xiao, Y. Tanshinone IIA reduces palmitate-induced apoptosis via inhibition of endoplasmic re-ticulum stress in HepG2 liver cells. Fundam. Clin. Pharmacol., 2020, 34(2), 249-262.
[http://dx.doi.org/10.1111/fcp.12510] [PMID: 31520549]
[23]
Liu, Y.; Tong, C.; Tang, Y.; Cong, P.; Liu, Y.; Shi, X.; Shi, L.; Zhao, Y.; Jin, H.; Li, J.; Hou, M. Tanshinone IIA alleviates blast-induced inflammation, oxidative stress and apoptosis in mice partly by inhibiting the PI3K/Akt/FoxO1 signaling path-way. Free Radic. Biol. Med., 2020, 152, 52-60.
[http://dx.doi.org/10.1016/j.freeradbiomed.2020.02.032] [PMID: 32131025]
[24]
Won, S.H.; Lee, H.J.; Jeong, S.J.; Lee, H.J.; Lee, E.O.; Jung, D.B.; Shin, J.M.; Kwon, T.R.; Yun, S.M.; Lee, M.H.; Choi, S.H.; Lü, J.; Kim, S.H. Tanshinone IIA induces mitochondria dependent apoptosis in prostate cancer cells in association with an inhibition of phosphoinositide 3-kinase/AKT path-way. Biol. Pharm. Bull., 2010, 33(11), 1828-1834.
[http://dx.doi.org/10.1248/bpb.33.1828] [PMID: 21048307]
[25]
Won, S.H.; Lee, H.J.; Jeong, S.J.; Lü, J.; Kim, S.H. Activation of p53 signaling and inhibition of androgen receptor mediate tanshinone IIA induced G1 arrest in LNCaP prostate cancer cells. Phytother. Res., 2012, 26(5), 669-674.
[http://dx.doi.org/10.1002/ptr.3616] [PMID: 21997969]
[26]
Chiu, S.C.; Huang, S.Y.; Chen, S.P.; Su, C.C.; Chiu, T.L.; Pang, C.Y. Tanshinone IIA inhibits human prostate cancer cells growth by induction of endoplasmic reticulum stress in vitro and in vivo. Prostate Cancer Prostatic Dis., 2013, 16(4), 315-322.
[http://dx.doi.org/10.1038/pcan.2013.38] [PMID: 24042854]
[27]
Lin, C.; Wang, L.; Wang, H.; Yang, L.; Guo, H.; Wang, X. Tanshinone IIA inhibits breast cancer stem cells growth in vitro and in vivo through attenuation of IL-6/STAT3/NF-kB signaling pathways. J. Cell. Biochem., 2013, 114(9), 2061-2070.
[http://dx.doi.org/10.1002/jcb.24553] [PMID: 23553622]
[28]
Tian, H.L.; Yu, T.; Xu, N.N.; Feng, C.; Zhou, L.Y.; Luo, H.W.; Chang, D.C.; Le, X.F.; Luo, K.Q. A novel compound modified from tanshinone inhibits tumor growth in vivovia activation of the intrinsic apoptotic pathway. Cancer Lett., 2010, 297(1), 18-30.
[http://dx.doi.org/10.1016/j.canlet.2010.04.020] [PMID: 20494511]
[29]
Pan, T.L.; Wang, P.W.; Hung, Y.C.; Huang, C.H.; Rau, K.M. Proteomic analysis reveals tanshinone IIA enhances apopto-sis of advanced cervix carcinoma CaSki cells through mito-chondria intrinsic and endoplasmic reticulum stress path-ways. Proteomics, 2013, 13(23-24), 3411-3423.
[http://dx.doi.org/10.1002/pmic.201300274] [PMID: 24167031]
[30]
Sukumari-Ramesh, S.; Bentley, J.N.; Laird, M.D.; Singh, N.; Vender, J.R.; Dhandapani, K.M. Dietary phytochemicals in-duce p53- and caspase-independent cell death in human neu-roblastoma cells. Int. J. Dev. Neurosci., 2011, 29(7), 701-710.
[http://dx.doi.org/10.1016/j.ijdevneu.2011.06.002] [PMID: 21704149]
[31]
Chien, S.Y.; Kuo, S.J.; Chen, Y.L.; Chen, D.R.; Cheng, C.Y.; Su, C.C. Tanshinone IIA inhibits human hepatocellular carci-noma J5 cell growth by increasing Bax and caspase 3 and de-creasing CD31 expression in vivo. Mol. Med. Rep., 2012, 5(1), 282-286.
[PMID: 22002472]
[32]
Yun, S.M.; Jeong, S.J.; Kim, J.H.; Jung, J.H.; Lee, H.J.; Sohn, E.J.; Lee, M.H.; Kim, S.H. Activation of c-Jun N-terminal ki-nase mediates tanshinone IIA-induced apoptosis in KBM-5 chronic myeloid leukemia cells. Biol. Pharm. Bull., 2013, 36(2), 208-214.
[http://dx.doi.org/10.1248/bpb.b12-00537] [PMID: 23370352]
[33]
Zhang, Y.; Chen, F. Reactive oxygen species (ROS), trouble-makers between nuclear factor-kappaB (NF-kappaB) and c-Jun NH(2)-terminal kinase (JNK). Cancer Res., 2004, 64(6), 1902-1905.
[http://dx.doi.org/10.1158/0008-5472.CAN-03-3361] [PMID: 15026320]
[34]
Ray, P.D.; Huang, B.W.; Tsuji, Y. Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell. Signal., 2012, 24(5), 981-990.
[http://dx.doi.org/10.1016/j.cellsig.2012.01.008] [PMID: 22286106]

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