Piperlongumine induces apoptosis and G2/M phase arrest in human osteosarcoma cells by regulating ROS/PI3K/Akt pathway

Abstract Background Diosmetin is a bioflavonoid compound naturally abundant in citrus fruits. It is found to perform a variety of activities, while its antitumor property in osteosarcoma, a malignant tumor with unmet clinical treatment, remained unknown. Methods Colony formation assay, cell cycle analysis and apoptosis analysis were conducted respectively to observe the effect of diosmetin on cell proliferation and apoptosis in human osteosarcoma cells. Western blot and immunoprecipitation were used to detect the expression of apoptotic molecules and activation of STAT3/c-Myc pathway in Saos-2 and U2SO cells. Results Diosmetin significantly inhibited cell proliferation, induced cell cycle arrest at G2/M phase and promoted cell apoptosis in both Saos-2 and U2SO cells. Moreover, Diosmetin downregulated the expression of anti-apoptotic protein Bcl-xL while upregulated the levels of pro-apoptotic proteins including cleaved Caspase-3, cleaved-PARP and Bax. Furthermore, diosmetin dose-dependently inhibited STAT3 phosphorylation, reduced the expression of its downstream protein c-Myc and impeded the interaction between STAT3 molecules. Conclusions These results suggest that diosmetin exerts anti-osteosarcoma effects by suppressing cell proliferation and inducing apoptosis via inhibiting the activation of STAT3/c-Myc signaling pathway, which provide the possibility for diosmetin to be a chemotherapeutic candidate for osteosarcoma.

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Xiao Jin Wan, a traditional Chinese herbal formula, inhibits proliferation via arresting cell cycle progression at the G2/M phase and promoting apoptosis via activating the mitochondrial-dependent pathway in U-2OS human osteosarcoma cells

International Journal of Oncology ◽

10.3892/ijo.2013.1795 ◽

2013 ◽

Vol 42 (3) ◽

pp. 1070-1080 ◽

Cited By ~ 5

Author(s):

GUANGWEN WU ◽

JIANFENG CHU ◽

ZHENGRONG HUANG ◽

JINXIA YE ◽

PANYU CHEN ◽

...

Keyword(s):

Cell Cycle Progression ◽

Herbal Formula ◽

Osteosarcoma Cells ◽

Cycle Progression ◽

Chinese Herbal Formula ◽

Human Osteosarcoma ◽

Chinese Herbal ◽

Human Osteosarcoma Cells ◽

M Phase ◽

Dependent Pathway

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Imperatorin induces autophagy and G0/G1 phase arrest via PTEN-PI3K-AKT-mTOR/p21 signaling pathway in human osteosarcoma cells in vitro and in vivo

Cancer Cell International ◽

10.1186/s12935-021-02397-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Minchao Lv ◽

Qingxin Xu ◽

Bei Zhang ◽

Zhiqiang Yang ◽

Jun Xie ◽

...

Keyword(s):

Signaling Pathway ◽

Bioinformatic Analysis ◽

Osteosarcoma Cells ◽

Human Osteosarcoma ◽

Cycle Arrest ◽

Phase Arrest ◽

Human Osteosarcoma Cells ◽

G1 Phase Arrest

Abstract Background Osteosarcoma is the third most common cancer in adolescence and the first common primary malignant tumor of bone. The long-term prognosis of osteosarcoma still remains unsatisfactory in the past decades. Therefore, development of novel therapeutic agents which are effective to osteosarcoma and are safe to normal tissue simultaneously is quite essential and urgent. Methods Firstly, MTT assay, cell colony formation assay, cell migration and invasion assays were conducted to evaluate the inhibitory effects of imperatorin towards human osteosarcoma cells. RNA-sequence assay and bioinformatic analysis were then performed to filtrate and assume the potential imperatorin-induced cell death route and signaling pathway. Moreover, quantitative real-time PCR assay, western blot assay and rescue experiments were conducted to confirm the assumptions of bioinformatic analysis. Finally, a subcutaneous tumor-transplanted nude mouse model was established and applied to evaluate the internal effect of imperatorin on osteosarcoma by HE and immunohistochemistry staining. Results Imperatorin triggered time-dependent and dose-dependent inhibition of tumor growth mainly by inducing autophagy promotion and G0/G1 phase arrest in vitro and in vivo. Besides, imperatorin treatment elevated the expression level of PTEN and p21, down-regulated the phosphorylation of AKT and mTOR. In contrast, the inhibition of PTEN using Bpv (HOpic), a potential and selective inhibitor of PTEN, concurrently rescued imperatorin-induced autophagy promotion, cell cycle arrest and inactivation of PTEN-PI3K-AKT-mTOR/p21 pathway. Conclusions This work firstly revealed that imperatorin induced autophagy and cell cycle arrest through PTEN-PI3K-AKT-mTOR/p21 signaling pathway by targeting and up-regulating PTEN in human osteosarcoma cells. Hence, imperatorin is a desirable candidate for clinical treatments of osteosarcoma.

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VS-5584 Inhibits Human Osteosarcoma Cells Growth by Induction of G1- phase Arrest through Regulating PI3K/mTOR and MAPK Pathways

Current Cancer Drug Targets ◽

10.2174/1568009620666200414150353 ◽

2020 ◽

Vol 20 (8) ◽

pp. 616-623 ◽

Cited By ~ 2

Author(s):

Jing-Yi Sun ◽

Ya-Jun Hou ◽

Hai-Juan Cui ◽

Cheng Zhang ◽

Ming-Feng Yang ◽

...

Keyword(s):

Cell Migration ◽

Signaling Pathway ◽

Tube Formation ◽

G1 Phase ◽

Mtor Signaling Pathway ◽

Osteosarcoma Cells ◽

Human Osteosarcoma ◽

Phase Arrest ◽

Human Osteosarcoma Cells ◽

G1 Phase Arrest

Background: Activation of PI3K/mTOR signaling pathway plays key role in the progression of human osteosarcoma. Studies have confirmed that VS-5584 was a novel inhibitor of PI3K/mTOR pathway, and displayed potential anticancer activity. Objective: To explore the anticancer effect and underlying mechanism of VS-5584 against the growth of human osteosarcoma cells. Methods: U2OS and MG-63 human osteosarcoma cells were cultured and the cytotoxicity, cell apoptosis in VS-5584-treated cells were explored by the CCK8 assay, flow cytometric analysis and western blot. Cell migration and tube formation were also employed to examine the anticancer potential. Results: The results showed that VS-5584 treatment dose-dependently inhibited the growth of U2OS and MG-63 cells by induction of G1-phase arrest through regulating p21, p27, Cyclin B1 and Cdc2. Further investigation revealed that VS-5584 treatment effectively inhibited the PI3K/mTOR signaling pathway and triggered MAPK phosphorylation. Moreover, VS-5584 treatment dramatically suppressed cell migration and tube formation of HUVECs, followed by the down-regulation of HIF-1α and VEGF. Conclusion: Our findings validated that VS-5584 may be a promising anticancer agent with potential application in the chemotherapy and chemoprevention of human osteosarcoma.

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Corrigendum to “CCT128930 induces G1-phase arrest and apoptosis and synergistically enhances the anticancer efficiency of VS5584 in human osteosarcoma cells” [Biomed. Pharmacother. 130 (2020) 110544]

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2020.110931 ◽

2020 ◽

Vol 132 ◽

pp. 110931

Author(s):

Jing-yi Sun ◽

Ya-jun Hou ◽

Yi-bo Yin ◽

Feng-ze Wang ◽

Ming-feng Yang ◽

...

Keyword(s):

G1 Phase ◽

Osteosarcoma Cells ◽

Human Osteosarcoma ◽

Phase Arrest ◽

Human Osteosarcoma Cells ◽

G1 Phase Arrest

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Diallyl Disulfide Induces Apoptosis and Autophagy in Human Osteosarcoma MG-63 Cells through the PI3K/Akt/mTOR Pathway

Molecules ◽

10.3390/molecules24142665 ◽

2019 ◽

Vol 24 (14) ◽

pp. 2665 ◽

Cited By ~ 8

Author(s):

Ziqi Yue ◽

Xin Guan ◽

Rui Chao ◽

Cancan Huang ◽

Dongfang Li ◽

...

Keyword(s):

Annexin V ◽

Mtor Pathway ◽

Diallyl Disulfide ◽

Osteosarcoma Cell ◽

Dependent Manner ◽

Osteosarcoma Cells ◽

Human Osteosarcoma ◽

Human Osteosarcoma Cells ◽

M Phase ◽

Induced Apoptosis

Diallyl disulfide (DADs), a natural organic compound, is extracted from garlic and scallion and has anti-tumor effects against various tumors. This study investigated the anti-tumor activity of DADs in human osteosarcoma cells and the mechanisms. MG-63 cells were exposed to DADs (0, 20, 40, 60, 80, and 100 μM) for different lengths of time (24, 48, and 72 h). The CCK8 assay results showed that DADs inhibited osteosarcoma cell viability in a dose-and time-dependent manner. FITC-Annexin V/propidium iodide staining and flow cytometry demonstrated that the apoptotic ratio increased and the cell cycle was arrested at the G2/M phase as the DADs concentration was increased. A Western blot analysis was employed to detect the levels of caspase-3, Bax, Bcl-2, LC3-II/LC3-I, and p62 as well as suppression of the mTOR pathway. High expression of LC3-II protein revealed that DADs induced formation of autophagosome. Furthermore, DADs-induced apoptosis was weakened after adding 3-methyladenine, demonstrating that the DADs treatment resulted in autophagy-mediated death of MG-63 cells. In addition, DADs depressed p-mTOR kinase activity, and the inhibited PI3K/Akt/mTOR pathway increased DADs-induced apoptosis and autophagy. In conclusion, our results reveal that DADs induced G2/M arrest, apoptosis, and autophagic death of human osteosarcoma cells by inhibiting the PI3K/Akt/mTOR signaling pathway.

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