Inhibitory effects of forkhead box L1 gene on osteosarcoma growth through the induction of cell cycle arrest and apoptosis

Chen, Xiao; Deng, Min; Ma, Li; Zhou, Jiansheng; Xiao, Yuzhou; Zhou, Xiaoxi; Zhang, Changchun; Wu, Min

doi:10.3892/or.2015.3969

Cited by 38 publications

(16 citation statements)

References 20 publications

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“…A series of novel caspase-related apoptosis-inducing pathways have been identified that may be targeted to control cancer, which have practical significance for the majority of tumors and thus, may result in breakthroughs with regard to the treatment of malignant tumors (24). The activation of caspase-9 and caspase-3 may underlie the apoptosis of fibroblasts in keloids (25). Furthermore, caspase-8 activates caspase-9 downstream of the apoptosis cascade to induce apoptosis (26).…”

Section: Discussionmentioning

confidence: 99%

Xanthohumol inhibits proliferation of laryngeal squamous cell carcinoma

Wang

Yin

et al. 2016

Oncology Letters

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Abstract. Xanthohumol is a flavonoid compound that exhibits antioxidant and anticancer effects, and is used to treat atherosclerosis. The aim of the present study was to investigate the effect of xanthohumol on the cell proliferation of laryngeal squamous cell carcinoma and to understand the mechanism of its action. The effects of xanthohumol on the cell viability and apoptosis rate of laryngeal squamous cell carcinoma SCC4 cells were assessed by Annexin V-fluorescein isothiocyanate/propidium iodide staining. In addition, the expression levels of pro-apoptotic proteins, caspase-3, caspase-8, caspase-9, poly ADP ribose polymerase (PARP) p53 and apoptosis-inducing factor (AIF), as well as anti-apoptotic markers, B-cell lymphoma 2 (Bcl-2) and myeloid cell leukemia 1 (Mcl-1), were analyzed by western blotting. The results revealed that treatment with 40 µM xanthohumol significantly inhibited the proliferation of SCC4 cells. Furthermore, xanthohumol treatment (40 µM) induced SCC4 cell apoptosis, as indicated by the significant increase in activity and expression of caspase-3, caspase-8, caspase-9, PARP, p53 and AIF. By contrast, the protein expression of Bcl-2 and Mcl-1 was significantly decreased following treatment with 40 µM xanthohumol. Taken together, the results of the present study indicated that xanthohumol mediates growth suppression and apoptosis induction, which was mediated via the suppression of Bcl-2 and Mcl-1 and activation of PARP, p53 and AIF signaling pathways. Therefore, future studies that investigate xanthohumol as a potential therapeutic agent for laryngeal squamous cell carcinoma are required.

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Section: Discussionmentioning

confidence: 99%

Xanthohumol inhibits proliferation of laryngeal squamous cell carcinoma

Wang

Yin

et al. 2016

Oncology Letters

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“…Emerging evidence has indicated that the expression of FOX genes, including FOXC2 27 , FOXF1 28 , FOXL1 29 , FOXM1 30 , 31 , FOXO1 32 , 33 and FOXP2 34 , is disrupted in osteosarcoma cells and primary tumor biopsy samples. As shown in Table 1 , according to their expression in osteosarcoma cells and primary tumor biopsy samples, these FOX genes can be divided into two groups: oncogenes and anti-oncogenes.…”

Section: Expression Of Fox Genes In Osteosarcomamentioning

confidence: 99%

“…As shown in Table 1 , according to their expression in osteosarcoma cells and primary tumor biopsy samples, these FOX genes can be divided into two groups: oncogenes and anti-oncogenes. Oncogenes primarily include FOXC2 , FOXM1 and FOXP2 , and the elevated expression level of these genes has been observed in osteosarcoma cells, which is positively correlated with tumor size, clinical stage, pathological facture, and distant metastasis 27 - 29 . Anti-oncogenes primarily include FOXF1 , FOXL1 and FOXO1 , and decreased or absent expression levels of these genes were examined in osteosarcoma cells and primary tumor biopsy samples 30 - 34 .…”

Section: Expression Of Fox Genes In Osteosarcomamentioning

confidence: 99%

“…Interestingly, recent studies have also indicated that FOXL1 is downregulated in osteosarcoma tissues and cell lines with poor prognosis 29 . Overexpression of FOXL1 in osteosarcoma U2OS cells inhibited cell proliferation and induced expression of p21 and p27, leading to U2OS cell arrest at the G1 phase (Figure 3 B) 29 . Moreover, FOXL1 overexpression induced cytochrome c release and disrupted mitochondrial transmembrane depolarization, thereby triggering apoptosis 29 .…”

Section: Roles Of Fox Genes In Osteosarcomamentioning

confidence: 99%

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The Emerging Roles of Forkhead Box (FOX) Proteins in Osteosarcoma

Zhang¹,

Duan²,

Song³

et al. 2017

J. Cancer

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Osteosarcoma is the most common bone cancer primarily occurring in children and young adults. Over the past few years, the deregulation of a superfamily transcription factors, known as forkhead box (FOX) proteins, has been demonstrated to contribute to the pathogenesis of osteosarcoma. Molecular mechanism studies have demonstrated that FOX family proteins participate in a variety of signaling pathways and that their expression can be regulated by multiple factors. The dysfunction of FOX genes can alter osteosarcoma cell differentiation, metastasis and progression. In this review, we summarized the evidence that FOX genes play direct or indirect roles in the development and progression of osteosarcoma, and evaluated the emerging role of FOX proteins as targets for therapeutic intervention.

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“…Therefore, P21 can function as a regulator of cell cycle progression at the G1 checkpoint (15). Recently, P21 was found to be frequently downregulated in osteosarcoma, and upregulation of P21 was shown to inhibit the proliferation of osteosarcoma cells (16,17). However, the mechanisms of the regulation of P21 expression in osteosarcoma cells have remained to be fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-93 promotes cell proliferation by directly targeting P21 in osteosarcoma cells

2017

Experimental and Therapeutic Medicine

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Abstract. MicroRNAs (miRNAs) are small, non-coding RNAs that are key regulators of gene expression by directly binding to the 3'-untranslated region of their target mRNAs, resulting in translational repression or degradation of mRNA. It has been demonstrated that miRNAs have key roles in a variety of human malignancies, including osteosarcoma. The present study aimed to assess the molecular mechanism of miR-93 in the regulation of osteosarcoma cell proliferation. Reverse-transcription quantitative PCR and western blot assays were used to examine mRNA and protein expression. An MTT assay and flow cytometry were performed to determine the cell proliferation and cell cycle distribution. A luciferase reporter assay was performed to confirm the direct targeting of cyclin-dependent kinase inhibitor 1A (CDKN1A), also known as P21, by miR-93, which was suggested by a bioinformatics analysis. The results showed that the expression of miR-93 was frequently and significantly increased in a total of 19 osteosarcoma tissues compared to their matched adjacent non-tumor tissues, and the upregulation of miR-93 was associated with the malignant progression of osteosarcoma. Furthermore, miR-93 was also upregulated in the human osteosarcoma cell lines Saos-2, U2OS, SW1353 and MG63 when compared with that in the human osteoblast cell line hFOB1.19. Transfection with miR-93 inhibitor significantly reduced the miR-93 levels and inhibited the proliferation of U2OS and MG63 osteosarcoma cells. The protein levels of P21 were negatively regulated by miR-93 in U2OS and MG63 cells. Knockdown of miR-93 caused cell cycle arrest at G1 stage in U2OS and MG63 cells, identical to the effect of P21 overexpression. Finally, P21 was found to be significantly downregulated in osteosarcoma tissues compared to their matched adjacent non-tumor tissues, suggesting that the inhibition of P21 may be due to increased miR-93 expression in osteosarcoma tissues. In conclusion, the present study demonstrated that miR-93 enhances the proliferation of osteosarcoma cells, at least in part via inhibiting P21 expression and thus promoting cell cycle progression.

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Inhibitory effects of forkhead box L1 gene on osteosarcoma growth through the induction of cell cycle arrest and apoptosis

Cited by 38 publications

References 20 publications

Xanthohumol inhibits proliferation of laryngeal squamous cell carcinoma

Xanthohumol inhibits proliferation of laryngeal squamous cell carcinoma

The Emerging Roles of Forkhead Box (FOX) Proteins in Osteosarcoma

MicroRNA-93 promotes cell proliferation by directly targeting P21 in osteosarcoma cells

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