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Int. J. Mol. Sci. 2018, 19(9), 2719; https://doi.org/10.3390/ijms19092719

Tanshinone IIA Attenuates Insulin Like Growth Factor 1 -Induced Cell Proliferation in PC12 Cells through the PI3K/Akt and MEK/ERK Pathways

1
Faculty of Health Science, University of Macau, Taipa, Macau 999078, China
2
School of Pharmaceutical Sciences, Sothern Medical University, Guangzhou 510515, China
3
School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China;sxy811@gmail.com (X.S.)
4
School of Pharmacy, Pharmacy Australia Centre of Excellence, The University of Queensland, Woolloongabba, Queensland 4102, Australia
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 2 August 2018 / Revised: 29 August 2018 / Accepted: 6 September 2018 / Published: 12 September 2018
(This article belongs to the Section Biochemistry)
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Abstract

The insulin like growth factor 1 (IGF-1) and its receptor (IGF-1R) facilitate tumor proliferation and progression. Tanshinone IIA (TSN) is an active diterpene quinone isolated from the roots of the herbal plant Salvia miltiorrhiza. TSN inhibits the proliferation of various types of cancer cells but its role in the IGF-1R-induced proliferation of pheochromocytoma (PC12) cells and the potential mechanisms are largely unknown. This study aims to investigate the anti-proliferative effect of TSN in PC12 cells and its role on IGF-1R signaling transduction. PC12 cells were treated with IGF-1 with or without TSN, methyl thiazolytetrazolium (MTT) assay, and cell counting kit-8 and flow cytometry were used to evaluate the proliferation of PC12 cells. The role of TSN on the apoptosis of PC12 cells were detected by flow cytometry as well. The effects of TSN and IGF-1 on the phosphorylation of IGF-1R, protein kinase B (Akt), extracellular-signal related kinase 1/2 (ERK1/2) and other downstream targets were analyzed by Western blotting analysis. Our results showed that IGF-1 promoted the growth of PC12 cells in a dose-dependent manner and increased the phosphorylation of IGF-1R, whereas TSN attenuated the effect of IGF-1. Interestingly, TSN did not induce cell apoptosis in PC12 cells. Moreover, TSN attenuated the phosphorylation of Akt and ERK1/2 induced by IGF-1, and the phosphorylation of glycogen synthase kinase-3β, forkhead box O3a (FOXO3a) and c-Raf were also inhibited by TSN. Furthermore, TSN inhibited cell growth induced by IGF-1 and blocked the activation of IGF-1R in SH-SY5Y cells. Taken together, TSN has an inhibitory effect on the proliferation of PC12 cells via down-regulation of the phosphorylated IGF-1R and its downstream signaling. View Full-Text
Keywords: Tanshinone IIA; antiproliferation; IGF-1R; Akt; ERK Tanshinone IIA; antiproliferation; IGF-1R; Akt; ERK
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Wang, H.; Su, X.; Fang, J.; Xin, X.; Zhao, X.; Gaur, U.; Wen, Q.; Xu, J.; Little, P.J.; Zheng, W. Tanshinone IIA Attenuates Insulin Like Growth Factor 1 -Induced Cell Proliferation in PC12 Cells through the PI3K/Akt and MEK/ERK Pathways. Int. J. Mol. Sci. 2018, 19, 2719.

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