Major Physiological Signaling Pathways in the Regulation of Cell Proliferation and Survival

Tang, Huifang; Xue, Gui-Rong

doi:10.1007/164_2017_4

Cited by 12 publications

(6 citation statements)

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“…Proliferation of these preadipocyte-like cells is enhanced, potentially due to a constitutive overactivation of the PI3K-pathway [18]. The PI3K/AKT/mTOR axis acts as a major growth factor signaling pathway regulating proliferation and survival [19]. In adipose tissue, PI3K signaling is essential for adipocyte differentiation [20].…”

Section: Discussionmentioning

confidence: 99%

The Novel Phosphatidylinositol-3-Kinase (PI3K) Inhibitor Alpelisib Effectively Inhibits Growth of PTEN-Haploinsufficient Lipoma Cells

Kirstein

Augustin

Penke

et al. 2019

Cancers

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Germline mutations in the tumor suppressor gene PTEN cause PTEN Hamartoma Tumor Syndrome (PHTS). Pediatric patients with PHTS frequently develop lipomas. Treatment attempts with the mTORC1 inhibitor rapamycin were unable to reverse lipoma growth. Recently, lipomas associated with PIK3CA-related overgrowth syndrome were successfully treated with the novel PI3K inhibitor alpelisib. Here, we tested whether alpelisib has growth-restrictive effects and induces cell death in lipoma cells. We used PTEN-haploinsufficient lipoma cells from three patients and treated them with alpelisib alone or in combination with rapamycin. We tested the effect of alpelisib on viability, proliferation, cell death, induction of senescence, adipocyte differentiation, and signaling at 1–100 µM alpelisib. Alpelisib alone or in combination with rapamycin reduced proliferation in a concentration- and time-dependent manner. No cell death but an induction of senescence was detected after alpelisib incubation for 72 h. Alpelisib treatment led to a reduced phosphorylation of AKT, mTOR, and ribosomal protein S6. Rapamycin treatment alone led to increased AKT phosphorylation. This effect could be reversed by combining rapamycin with alpelisib. Alpelisib reduced the size of lipoma spheroids by attenuating adipocyte differentiation. Since alpelisib was well tolerated in first clinical trials, this drug alone or in combination with rapamycin is a potential new treatment option for PHTS-related adipose tissue overgrowth.

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Section: Discussionmentioning

confidence: 99%

The Novel Phosphatidylinositol-3-Kinase (PI3K) Inhibitor Alpelisib Effectively Inhibits Growth of PTEN-Haploinsufficient Lipoma Cells

Kirstein

Augustin

Penke

et al. 2019

Cancers

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“…These consistently indicate that biochanin-A-induced anti-proliferation and anti-migration are mediated by the expressional downregulation and inactivation of MMP-2 and MMP-9 through the suppression of p38 MAPK and NF-κB cellular signaling pathways in FaDu cells. In addition, PI3K/Akt signaling is closely associated with cell proliferation, survival, growth and metastasis (37,38). Recent studies have reported that the suppression of PI3K/Akt signaling enhances cytotoxicity through the inhibition of the mTOR signaling pathway in various cancers such as breast and colorectal cancer (39)(40)(41).…”

Section: Discussionmentioning

confidence: 99%

Biochanin-A induces apoptosis and suppresses migration in FaDu human pharynx squamous carcinoma cells

et al. 2017

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The aim of the present study was to investigate biochanin-A-induced anticancer effects and their cellular signaling pathway in FaDu pharyngeal squamous carcinoma cells. Biochanin-A induced cell death through increased cytotoxicity of FaDu cells in a dose- and time-dependent manner. The number of cells with nucleus condensation and the apoptotic population were increased in the FaDu cells stimulated with biochanin-A for 24 h. Furthermore, extrinsic apoptotic factors such as FasL and their downstream target caspase-8 were increased and activated in the FaDu cells treated with biochanin-A in a dose-dependent manner. Moreover, biochanin-A decreased the expression of intrinsic anti-apoptotic factors such as Bcl-2 and Bcl-xL, and increased the level and activation of intrinsic apoptotic factors such as Bad and caspase-9. Finally, biochanin-A induced the activation of caspase-3 and Poly(ADP ribose) polymerase (PARP) in FaDu cells. Our results suggest that biochanin-A-induced apoptosis was mediated by death receptor mediated-extrinsic and mitochondria-dependent intrinsic apoptotic signaling pathways. Biochanin-A also inhibited wound healing migration and proliferation of FaDu cells via the downregulation and inactivation of matrix metalloproteinase-2 and -9 that are mediated by the suppression of p38, mitogen activated protein kinase (MAPK), NF-κB and Akt cellular signaling pathways. Therefore, these data suggest that the biochanin-A may act as a potential chemotherapeutic compound to treat head and neck cancer.

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“…The PI3K/AKT signaling pathway is thought to be one of the most important oncogenic pathways in human osteosarcoma, and plays a fundamental role in maintaining cell viability (19,20). The JAK/STAT signaling pathway is involved in several cellar processes, including cell proliferation, apoptosis and differentiation (21). JAK2 acts as an upstream kinase to recruit STAT3 monomers in the cytosol, allowing inactive STAT3 to form active dimers that are transferred to the nucleus and bind to DNA, leading to the transcription of target genes (22,23).…”

Section: Discussionmentioning

confidence: 99%

Interleukin‑22 modulates cisplatin sensitivity of osteosarcoma cells by regulating the STAT3 signaling pathway

Zhang

et al. 2019

Exp Ther Med

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The present study aimed to investigate the regulatory mechanisms by which interleukin (IL)-22 regulates cisplatin (DDP) sensitivity in osteosarcoma cells. Firstly, reverse transcription-quantitative (RT-q) PCR and western blotting demonstrated that IL-22 expression was significantly increased in osteosarcoma tissues and cell lines compared with the adjacent normal tissues and the normal osteoblast hFOB1.19 cells. Subsequently, the MG63 osteosarcoma cell line and cisplatin-resistant MG63/DDP osteosarcoma cell line were treated with different concentrations of cisplatin (2.5, 5.0, 10, 20, 40 and 80 µg/ml), and the half maximal inhibitory concentration (IC 50) was calculated based on the MTT assay. The results showed that the IC 50 of DDP in MG63/DDP cells was significantly higher than that in MG63 cells. Furthermore, IL-22 expression was higher in MG63/DDP cells compared with MG63 cells. Subsequently, the effects of IL-22 downregulation and overexpression on MG63/DDP and MG63 cells were assessed using the MTT assay, flow cytometry, RT-qPCR and western blotting. The IL-22 small interfering (si) RNA in MG63/DDP cells significantly decreased the IC 50 of DDP and decreased the cell viability of MG63/DDP cells. Furthermore, IL-22 RNA interference decreased BCl-2 expression and phosphorylation of STAT3, induced apoptosis, and increased the expression of Bax and cleaved caspase-3. The IL-22 overexpression plasmid had opposite effects to the observations in IL-22 siRNA-transfected MG63 cells. Overall, the present study indicated that IL-22 regulated the cell viability and apoptosis of osteosarcoma cells by regulating the activation of the STAT3 signaling pathway and affecting the expression of apoptosis-associated genes, and thereby mediating the sensitivity of osteosarcoma cells to cisplatin.

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Major Physiological Signaling Pathways in the Regulation of Cell Proliferation and Survival

Cited by 12 publications

References 100 publications

The Novel Phosphatidylinositol-3-Kinase (PI3K) Inhibitor Alpelisib Effectively Inhibits Growth of PTEN-Haploinsufficient Lipoma Cells

The Novel Phosphatidylinositol-3-Kinase (PI3K) Inhibitor Alpelisib Effectively Inhibits Growth of PTEN-Haploinsufficient Lipoma Cells

Biochanin-A induces apoptosis and suppresses migration in FaDu human pharynx squamous carcinoma cells

Interleukin‑22 modulates cisplatin sensitivity of osteosarcoma cells by regulating the STAT3 signaling pathway

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