Andrographolide induces apoptosis in human osteosarcoma cells via the ROS/JNK pathway

Wang, Shengdong; Li, Hengyuan; Chen, Shi; Wang, Zenan; Yao, Yuhong; Chen, Tao; Ye, Zhaoming; Lin, Peng

doi:10.3892/ijo.2020.5032

Cited by 27 publications

(28 citation statements)

References 53 publications

(55 reference statements)

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“…Wang et al. 42 have shown that andrographolide induced OS cell apoptosis via ROS production and downstream JNK activation. Similarly, hyperthermia-induced OS cell apoptosis was associated with ROS production.…”

Section: Discussionmentioning

confidence: 99%

MAFG-driven osteosarcoma cell progression is inhibited by a novel miRNA miR-4660

Shan

Zhu

Yao

et al. 2021

Molecular Therapy - Nucleic Acids

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Osteosarcoma (OS) is the most common primary bone malignancy in the adolescent population. MAFG (v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog G) forms a heterodimer with Nrf2 (NF-E2-related factor 2), binding to antioxidant response element (ARE), which is required for Nrf2 signaling activation. We found that MAFG mRNA and protein expression is significantly elevated in human OS tissues as well as in established and primary human OS cells. In human OS cells, MAGF silencing or knockout (KO) largely inhibited OS cell growth, proliferation, and migration, simultaneously inducing oxidative injury and apoptosis activation. Conversely, ectopic overexpression of MAFG augmented OS cell progression in vitro . MicroRNA-4660 (miR-4660) directly binds the 3′ untranslated region (UTR) of MAFG mRNA in the cytoplasm of OS cells. MAFG 3′ UTR luciferase activity and expression as well as OS cell growth were largely inhibited with forced miR-4660 overexpression but augmented with miR-4660 inhibition. In vivo , MAGF short hairpin RNA (shRNA) or forced overexpression of miR-4660 inhibited subcutaneous OS xenograft growth in severe combined immunodeficient mice. Furthermore, MAFG silencing or miR-4660 overexpression inhibited OS xenograft in situ growth in proximal tibia of the nude mice. In summary, MAFG overexpression-driven OS cell progression is inhibited by miR-4660. The miR-4660-MAFG axis could be novel therapeutic target for human OS.

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Section: Discussionmentioning

confidence: 99%

MAFG-driven osteosarcoma cell progression is inhibited by a novel miRNA miR-4660

Shan

Zhu

Yao

et al. 2021

Molecular Therapy - Nucleic Acids

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“…Some studies have also reported that Andro contributes significantly to the suppression of the apoptotic process (Xiang et al, 2020;Khan et al, 2021). For instance, in human osteosarcoma, the apoptotic process has been caused by Andro via ROS/JNK cascade (Wang et al, 2020). Apoptosis is a key determinant of cells and tissues' survival (Xu et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Positive Effect of Andrographolide Induced Autophagy on Random-Pattern Skin Flaps Survival

et al. 2021

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Random-pattern skin flap replantation is generally used in the reconstruction of surgical tissues and covering a series of skin flap defects. However, ischemia often occurs at the flap distal parts, which lead to flap necrosis. Previous studies have shown that andrographolide (Andro) protects against ischemic cardiovascular diseases, but little is known about the effect of Andro on flap viability. Thus, our study aimed to building a model of random-pattern skin flap to understand the mechanism of Andro-induced effects on flap survival. In this study, fifty-four mice were randomly categorized into the control, Andro group, and the Andro+3-methyladenine group. The skin flap samples were obtained on postoperative day 7. Subsequently, the tissue samples were underwent a series of evaluations such as changes in the appearance of flap tissue, the intensity of blood flow, and neovascularization density of skin flap. In our study, the results revealed that Andro enhanced the viability of random skin flaps by enhancing angiogenesis, inhibiting apoptosis, and reducing oxidative stress. Furthermore, our results have also demonstrated that the administration of Andro caused an elevation in the autophagy, and these remarkable impact of Andro were reversed by 3-methyladenine (3-MA), the most common autophagy inhibitor. Together, our data proves novel evidence that Andro is a potent modulator of autophagy capable of significantly increasing random-pattern skin flap survival.

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“…In turn, JNK may play a dual role in cancer cell survival, but preferentially exerts a pro-apoptotic effect [ 33 , 46 , 48 ]. Mounting evidence indicates that activation of JNK kinase in response to various anti-cancer agents may contribute to OS cell death [ 49 , 50 ]. In our study, AKG induced phosphorylation of JNK in the Saos-2 cells.…”

Section: Discussionmentioning

confidence: 99%

Alpha Ketoglutarate Exerts In Vitro Anti-Osteosarcoma Effects through Inhibition of Cell Proliferation, Induction of Apoptosis via the JNK and Caspase 9-Dependent Mechanism, and Suppression of TGF-β and VEGF Production and Metastatic Potential of Cells

Kaławaj

Sławińska-Brych

Mizerska-Kowalska

et al. 2020

IJMS

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Osteosarcoma (OS) is the most common type of primary bone tumor. Currently, there are limited treatment options for metastatic OS. Alpha-ketoglutarate (AKG), i.e., a multifunctional intermediate of the Krebs cycle, is one of the central metabolic regulators of tumor fate and plays an important role in cancerogenesis and tumor progression. There is growing evidence suggesting that AKG may represent a novel adjuvant therapeutic opportunity in anti-cancer therapy. The present study was intended to check whether supplementation of Saos-2 and HOS osteosarcoma cell lines (harboring a TP53 mutation) with exogenous AKG exerted an anti-cancer effect. The results revealed that AKG inhibited the proliferation of both OS cell lines in a concentration-dependent manner. As evidenced by flow cytometry, AKG blocked cell cycle progression at the G1 stage in both cell lines, which was accompanied by a decreased level of cyclin D1 in HOS and increased expression of p21Waf1/Cip1 protein in Saos-2 cells (evaluated with the ELISA method). Moreover, AKG induced apoptotic cell death and caspase-3 activation in both OS cell lines (determined by cytometric analysis). Both the immunoblotting and cytometric analysis revealed that the AKG-induced apoptosis proceeded predominantly through activation of an intrinsic caspase 9-dependent apoptotic pathway and an increased Bax/Bcl-2 ratio. The apoptotic process in the AKG-treated cells was mediated via c-Jun N-terminal protein kinase (JNK) activation, as the specific inhibitor of this kinase partially rescued the cells from apoptotic death. In addition, the AKG treatment led to reduced activation of extracellular signal-regulated kinase (ERK1/2) and significant inhibition of cell migration and invasion in vitro concomitantly with decreased production of pro-metastatic transforming growth factor β (TGF-β) and pro-angiogenic vascular endothelial growth factor (VEGF) in both OS cell lines suggesting the anti-metastatic potential of this compound. In conclusion, we showed the anti-osteosarcoma potential of AKG and provided a rationale for a further study of the possible application of AKG in OS therapy.

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Andrographolide induces apoptosis in human osteosarcoma cells via the ROS/JNK pathway

Cited by 27 publications

References 53 publications

MAFG-driven osteosarcoma cell progression is inhibited by a novel miRNA miR-4660

MAFG-driven osteosarcoma cell progression is inhibited by a novel miRNA miR-4660

Positive Effect of Andrographolide Induced Autophagy on Random-Pattern Skin Flaps Survival

Alpha Ketoglutarate Exerts In Vitro Anti-Osteosarcoma Effects through Inhibition of Cell Proliferation, Induction of Apoptosis via the JNK and Caspase 9-Dependent Mechanism, and Suppression of TGF-β and VEGF Production and Metastatic Potential of Cells

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