Tanshinone IIA Improves Depression-like Behavior in Mice by Activating the ERK-CREB-BDNF Signaling Pathway

Lü, Jiaqi; Zhou, Hang; Meng, Danyang; Pan, Kailing; Wan, Bo; Miao, Zhigang

doi:10.1016/j.neuroscience.2020.01.026

Cited by 46 publications

(16 citation statements)

References 54 publications

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“…However, the underlying mechanisms need further elucidation. A panel of protein kinases has been demonstrated as potential targets in Tan IIA-treated tumor cells, such as PI3K/Akt, MAPK, and mTOR 40,44,45 . In the present study, with a molecular modeling screening, we identified that Tan IIA is a candidate inhibitor for Aurora B kinase in an ATP competitive binding-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

Targeting Aurora B kinase with Tanshinone IIA suppresses tumor growth and overcomes radioresistance

Liu

Qin

et al. 2021

Cell Death Dis

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Aurora B kinase is aberrantly overexpressed in various tumors and shown to be a promising target for anti-cancer therapy. In human oral squamous cell carcinoma (OSCC), the high protein level of Aurora B is required for maintaining of malignant phenotypes, including in vitro cell growth, colony formation, and in vivo tumor development. By molecular modeling screening of 74 commercially available natural products, we identified that Tanshinone IIA (Tan IIA), as a potential Aurora B kinase inhibitor. The in silico docking study indicates that Tan IIA docks into the ATP-binding pocket of Aurora B, which is further confirmed by in vitro kinase assay, ex vivo pull-down, and ATP competitive binding assay. Tan IIA exhibited a significant anti-tumor effect on OSCC cells both in vitro and in vivo, including reduction of Aurora B and histone H3 phosphorylation, induction of G2/M cell cycle arrest, increase the population of polyploid cells, and promotion of apoptosis. The in vivo mouse model revealed that Tan IIA delayed tumor growth of OSCC cells. Tan IIA alone or in combination with radiation overcame radioresistance in OSCC xenograft tumors. Taken together, our data indicate that Tan IIA is an Aurora B kinase inhibitor with therapeutic potentials for cancer treatment.

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Section: Discussionmentioning

confidence: 99%

Targeting Aurora B kinase with Tanshinone IIA suppresses tumor growth and overcomes radioresistance

Liu

Qin

et al. 2021

Cell Death Dis

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show abstract

“…Furthermore, Tan IIA enhanced the tumor-killing effect when combined with chemotherapy agents or radiotherapy (40,41). A panel of protein kinases has been demonstrated as potential targets in Tan IIA-treated tumor cells, such as PI3K/Akt, MAPK, and mTOR (41)(42)(43). In the present study, with a molecular modeling screening, we identi ed that Tan IIA is a candidate inhibitor for Aurora B kinase in an ATP competitive binding dependent manner.…”

Section: Discussionmentioning

confidence: 61%

Targeting Aurora B kinase with Tanshinone IIA Suppresses Tumor Growth and Overcomes Radioresistance

Gao

liu

et al. 2020

Preprint

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Background Aurora B kinase is aberrantly overexpressed in various tumors and shown to be a promising target for anti-cancer therapy. Methods A customized natural product library was used for natural compound screening through Molecular modeling. The expression of Aurora B in oral squamous cell carcinoma (OSCC) and the inhibitory effect of Tanshinone IIA (Tan IIA) on OSCC were examined by MTS and colony formation assays, immunoblot, immunofluorescence, immunohistochemical staining, and in vivo xenograft experiment. Results Aurora B is overexpressed in OSCC tumor tissues and cell lines. Knockdown of Aurora B inhibited the malignant phenotypes of OSCC cells in vitro and in vivo. With a molecular modeling screening of 74 commercially available natural products, we identified that Tan IIA, as a potential Aurora B kinase inhibitor. Tan IIA exhibited a significant anti-tumor effect on OSCC cells both in vitro and in vivo, including reduction of Aurora B and histone H3 phosphorylation, induction of G2/M cell cycle arrest, increase the population of polyploid cells, and promotion of apoptosis. The in vivo mouse model revealed that Tan IIA delayed tumor growth of OSCC cells. Tan IIA alone or in combination with radiation overcame radioresistance in OSCC xenograft tumors. Conclusion Our data indicates that targeting Aurora B kinase signaling is a promising anti-tumor strategy for OSCC treatment.

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“… 37 Many studies have reported that this pathway was related to the prevention of depressive-like behaviors. 38 , 39 Having established the increased BDNF by GAA, we assumed that the ERK/CREB pathway was also mediated by GAA. Here, we found that this pathway was inactivated in PSD rats after CUMS, which was also consistent with previous reports.…”

Section: Discussionmentioning

confidence: 99%

Ganoderic Acid A-Mediated Modulation of Microglial Polarization is Involved in Depressive-Like Behaviors and Neuroinflammation in a Rat Model of Post-Stroke Depression

Zhang

Sui

2021

NDT

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Background Post-stroke depression (PSD) is a common complication after stroke. Ganoderic acid A (GAA), one of the main bioactive Ganoderma triterpenoids, exerts preventive and therapeutic effects in many diseases. However, the function of GAA in PSD has not been well studied. Methods PSD model was established via stimulating rats with chronic unpredictable mild stress stimulations (CUMS) after middle cerebral artery occlusion (MCAO). Rats were treated with GAA before CUMS. Depressive-like behaviors were investigated by body weight alteration, open field test (OFT), and sucrose preference test (SPT). Neuronal damage was evaluated by hematoxylin and eosin (HE) staining and Western blotting. Inflammation was detected by enzyme-linked immunosorbent assay (ELISA) and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Microglial polarization was analyzed via qRT-PCR and Western blotting. The extracellular signal-regulated kinase (ERK)/cAMP-response element-binding protein (CREB) pathway was analyzed by Western blotting, and inactivated by the inhibitor PD98059 (PD). Results GAA attenuated PSD-induced depressive-like behaviors in rats. GAA mitigated PSD-induced neuronal damage and reduced BDNF and NGF levels in the cerebral hippocampus. GAA weakened PSD-induced inflammatory response in the cerebral hippocampus. GAA prevented pro-inflammatory (M1) polarization and promoted anti-inflammatory (M2) polarization, as indicated by decreased iNOS and CD86 levels and increased Arg-1 and CD206 levels. GAA restored the PSD-induced inactivation of the ERK/CREB pathway. GAA regulated M1/M2 microglial polarization by activating the ERK/CREB pathway. Conclusion GAA alleviated the depressive-like behaviors and brain inflammation in PSD rats, indicating its potential for PSD therapy.

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Tanshinone IIA Improves Depression-like Behavior in Mice by Activating the ERK-CREB-BDNF Signaling Pathway

Cited by 46 publications

References 54 publications

Targeting Aurora B kinase with Tanshinone IIA suppresses tumor growth and overcomes radioresistance

Targeting Aurora B kinase with Tanshinone IIA suppresses tumor growth and overcomes radioresistance

Targeting Aurora B kinase with Tanshinone IIA Suppresses Tumor Growth and Overcomes Radioresistance

Ganoderic Acid A-Mediated Modulation of Microglial Polarization is Involved in Depressive-Like Behaviors and Neuroinflammation in a Rat Model of Post-Stroke Depression

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