Generic placeholder image

Current Pharmaceutical Biotechnology


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

General Research Article

Morusin Inhibits Human Osteosarcoma via the PI3K-AKT Signaling Pathway

Author(s): Yong Zhang, Qiuyan Weng, Jianming Chen and Jinming Han*

Volume 21, Issue 13, 2020

Page: [1402 - 1409] Pages: 8

DOI: 10.2174/1389201021666200416093457

Price: $65


Objective: Osteosarcoma is considered as one of the most common types of bone tumors, which occurs among adolescents and children.

Methods: Current therapy strategies still have limited effectiveness therefore, the development of new therapies is urgent. Morusin is a compound isolated from Morus australis (Moraceae). Many studies have reported its anti-tumor effect on several tumor types. However, its role in osteosarcoma is still unclear.

Results: In this study, we determined that morusin significantly suppresses the proliferation and promotes the apoptosis of osteosarcoma cells. Furthermore, the migration and invasion of osteosarcoma were reduced after exposure to morusin. The deep mechanism was determined to be the inhibition of the PI3K/AKT signaling pathway.

Conclusion: In conclusion, our study indicates morusin as a potential candidate for osteosarcoma therapy.

Keywords: Morusin, osteosarcoma, PI3K/AKT, therapy, MMPs, human osteosarcoma.

« Previous
Graphical Abstract
Ottaviani, G.; Jaffe, N. The epidemiology of osteosarcoma. Cancer Treat. Res., 2009, 152, 3-13.
[] [PMID: 20213383]
Marina, N.; Gebhardt, M.; Teot, L.; Gorlick, R. Biology and therapeutic advances for pediatric osteosarcoma. Oncologist, 2004, 9(4), 422-441.
[] [PMID: 15266096]
Shen, A.; Zhang, Y.; Yang, H.; Xu, R.; Huang, G. Overexpression of ZEB1 relates to metastasis and invasion in osteosarcoma. J. Surg. Oncol., 2012, 105(8), 830-834.
[] [PMID: 22213004]
Lin, Y.M.; Chang, Z.L.; Liao, Y.Y.; Chou, M.C.; Tang, C.H. IL-6 promotes ICAM-1 expression and cell motility in human osteosarcoma. Cancer Lett., 2013, 328(1), 135-143.
[] [PMID: 22939995]
Himelstein, B.P.; Asada, N.; Carlton, M.R.; Collins, M.H. Matrix metalloproteinase-9 (MMP-9) expression in childhood osseous osteosarcoma. Med. Pediatr. Oncol., 1998, 31(6), 471-474.
[<471: AID-MPO2>3.0.CO;2-M] [PMID: 9835898]
Cho, H.J.; Lee, T.S.; Park, J.B.; Park, K.K.; Choe, J.Y.; Sin, D.I.; Park, Y.Y.; Moon, Y.S.; Lee, K.G.; Yeo, J.H.; Han, S.M.; Cho, Y.S.; Choi, M.R.; Park, N.G.; Lee, Y.S.; Chang, Y.C. Disulfiram suppresses invasive ability of osteosarcoma cells via the inhibition of MMP-2 and MMP-9 expression. J. Biochem. Mol. Biol., 2007, 40(6), 1069-1076.
[PMID: 18047805]
Zhang, J.; Yu, X.H.; Yan, Y.G.; Wang, C.; Wang, W.J. PI3K/Akt signaling in osteosarcoma. Clin. Chim. Acta, 2015, 444, 182-192.
[] [PMID: 25704303]
Dong, Y.; Liang, G.; Yuan, B.; Yang, C.; Gao, R.; Zhou, X. MALAT1 promotes the proliferation and metastasis of osteosarcoma cells by activating the PI3K/Akt pathway. Tumour Biol., 2015, 36(3), 1477-1486.
[] [PMID: 25431257]
Tsubaki, M.; Satou, T.; Itoh, T.; Imano, M.; Ogaki, M.; Yanae, M.; Nishida, S. Reduction of metastasis, cell invasion, and adhesion in mouse osteosarcoma by YM529/ONO-5920-induced blockade of the Ras/MEK/ERK and Ras/PI3K/Akt pathway. Toxicol. Appl. Pharmacol., 2012, 259(3), 402-410.
[] [PMID: 22326785]
Jin, S.; Pang, R.P.; Shen, J.N.; Huang, G.; Wang, J.; Zhou, J.G. Grifolin induces apoptosis via inhibition of PI3K/AKT signalling pathway in human osteosarcoma cells. Apoptosis, 2007, 12(7), 1317-1326.
[] [PMID: 17333316]
Carol, H.; Morton, C.L.; Gorlick, R.; Kolb, E.A.; Keir, S.T.; Reynolds, C.P.; Kang, M.H.; Maris, J.M.; Billups, C.; Smith, M.A.; Houghton, P.J.; Lock, R.B. Initial testing (stage 1) of the Akt inhibitor GSK690693 by the pediatric preclinical testing program. Pediatr. Blood Cancer, 2010, 55(7), 1329-1337.
[] [PMID: 20740623]
Ren, W.; Liu, Y.; Wan, S.; Fei, C.; Wang, W.; Chen, Y.; Zhang, Z.; Wang, T.; Wang, J.; Zhou, L.; Weng, Y.; He, T.; Zhang, Y. BMP9 inhibits proliferation and metastasis of HER2-positive SK-BR-3 breast cancer cells through ERK1/2 and PI3K/AKT pathways. PLoS One, 2014, 9(5)e96816
[] [PMID: 24805814]
Yao, C.; Wei, J.J.; Wang, Z.Y.; Ding, H.M.; Li, D.; Yan, S.C.; Yang, Y.J.; Gu, Z.P. Perifosine induces cell apoptosis in human osteosarcoma cells: New implication for osteosarcoma therapy? Cell Biochem. Biophys., 2013, 65(2), 217-227.
[] [PMID: 23015227]
Tseng, T.H.; Chuang, S.K.; Hu, C.C.; Chang, C.F.; Lee, Y.J. The synthesis of morusin as a potent antitumor agent. Tetrahedron, 2010, 66(6), 1335-1340.
Xue, J.; Li, R.; Zhao, X.; Ma, C.; Lv, X.; Liu, L.; Liu, P. Morusin induces paraptosis-like cell death through mitochondrial calcium overload and dysfunction in epithelial ovarian cancer. Chem. Biol. Interact., 2018, 283, 59-74.
[] [PMID: 29421517]
Kim, C.; Kim, J.H.; Oh, E.Y.; Nam, D.; Lee, S.G.; Lee, J.; Kim, S.H.; Shim, B.S.; Ahn, K.S. Blockage Of Stat3 Signaling Pathway By Morusin Induces Apoptosis And Inhibits Invasion In Human Pancreatic Tumor Cells. Pancreas, 2016, 45(3), 409-419.
[] [PMID: 26646273]
Lim, S.L.; Park, S.Y.; Kang, S.; Park, D.; Kim, S.H.; Um, J.Y.; Jang, H.J.; Lee, J.H.; Jeong, C.H.; Jang, J.H.; Ahn, K.S.; Lee, S.G. Morusin induces cell death through inactivating STAT3 signaling in prostate cancer cells. Am. J. Cancer Res., 2014, 5(1), 289-299.
[PMID: 25628938]
Li, H.; Wang, Q.; Dong, L.; Liu, C.; Sun, Z.; Gao, L.; Wang, X. Morusin suppresses breast cancer cell growth in vitro and in vivo through C/EBPβ and PPARγ mediated lipoapoptosis. J. Exp. Clin. Cancer Res., 2015, 34(1), 137.
[] [PMID: 26538209]
Lee, J.C.; Won, S.J.; Chao, C.L.; Wu, F.L.; Liu, H.S.; Ling, P.; Lin, C.N.; Su, C.L. Morusin induces apoptosis and suppresses NF-kappaB activity in human colorectal cancer HT-29 cells. Biochem. Biophys. Res. Commun., 2008, 372(1), 236-242.
[] [PMID: 18485277]
Stacey, D.W. Cyclin D1 serves as a cell cycle regulatory switch in actively proliferating cells. Curr. Opin. Cell Biol., 2003, 15(2), 158-163.
[] [PMID: 12648671]
Shiomi, T.; Okada, Y. MT1-MMP and MMP-7 in invasion and metastasis of human cancers. Cancer Metastasis Rev., 2003, 22(2-3), 145-152.
[] [PMID: 12784993]
Sounni, N.E.; Rozanov, D.V.; Remacle, A.G.; Golubkov, V.S.; Noel, A.; Strongin, A.Y. Timp-2 binding with cellular MT1-MMP stimulates invasion-promoting MEK/ERK signaling in cancer cells. Int. J. Cancer, 2010, 126(5), 1067-1078.
[PMID: 19551841]
Misao, J.; Hayakawa, Y.; Ohno, M.; Kato, S.; Fujiwara, T.; Fujiwara, H. Expression of bcl-2 protein, an inhibitor of apoptosis, and Bax, an accelerator of apoptosis, in ventricular myocytes of human hearts with myocardial infarction. Circulation, 1996, 94(7), 1506-1512.
[] [PMID: 8840837]
Li, H.; Zhu, H.; Xu, C.J.; Yuan, J. Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell, 1998, 94(4), 491-501.
[] [PMID: 9727492]
Gianinazzi, C.; Grandgirard, D.; Imboden, H.; Egger, L.; Meli, D.N.; Bifrare, Y.D.; Joss, P.C.; Täuber, M.G.; Borner, C.; Leib, S.L. Caspase-3 mediates hippocampal apoptosis in pneumococcal meningitis. Acta Neuropathol., 2003, 105(5), 499-507.
[] [PMID: 12677451]
Guo, Q.; Jin, Z.; Yuan, Y.; Liu, R.; Xu, T.; Wei, H.; Xu, X.; He, S.; Chen, S.; Shi, Z.; Hou, W.; Hua, B. New mechanisms of tumor-associated macrophages on promoting tumor progression: recent research advances and potential targets for tumor immunotherapy. J. Immunol. Res., 2016.20169720912
[] [PMID: 27975071]
Cao, J.; Han, X.; Qi, X.; Jin, X.; Li, X. TUG1 promotes osteosarcoma tumorigenesis by upregulating EZH2 expression via miR-144-3p. Int. J. Oncol., 2017, 51(4), 1115-1123.
[] [PMID: 28902349]
Zhao, G.Y.; Cai, C.K.; Yang, T.T.; Qiu, X.X.; Liao, B.; Li, W.; Ji, Z.W.; Zhao, J.; Zhao, H.; Guo, M.J. Correction: MicroRNA-221 induces cell survival and cisplatin resistance through PI3K/Akt pathway in human osteosarcoma. PLoS One, 2013, 8(5)
Resnitzky, D.; Reed, S.I. Different roles for cyclins D1 and E in regulation of the G1-to-S transition. Mol. Cell. Biol., 1995, 15(7), 3463-3469.
[] [PMID: 7791752]
Kline, C.L.B. Van; Den Heuvel, A.P.J.; Allen, J.E.; Prabhu, V.V.; Dicker, D.T.; El-Deiry, W.S. ONC201 kills solid tumor cells by triggering an integrated stress response dependent on ATF4 activation by specific eIF2? kinases. Sci. Signal., 2016, 9(415), ra18-ra18.
[] [PMID: 26884600]
Li, J.; Xu, B.; Chen, Z.; Zhou, C.; Liao, L.; Qin, Y.; Yang, C.; Zhang, X.; Hu, Z.; Sun, L.; Zhu, D.; Xie, P. PI3K/AKT/JNK/p38 signalling pathway-mediated neural apoptosis in the prefrontal cortex of mice is involved in the antidepressant-like effect of pioglitazone. Clin. Exp. Pharmacol. Physiol., 2018, 45(6), 525-535.
[] [PMID: 29359338]
Li, L.; Wang, X.; Sharvan, R.; Gao, J.; Qu, S. Berberine could inhibit thyroid carcinoma cells by inducing mitochondrial apoptosis, G0/G1 cell cycle arrest and suppressing migration via PI3K-AKT and MAPK signaling pathways. Biomed. Pharmacother., 2017, 95, 1225-1231.
[] [PMID: 28931215]

Rights & Permissions Print Export Cite as
© 2024 Bentham Science Publishers | Privacy Policy