PI3K/AKT signaling pathway involvement in fluoride-induced apoptosis in C2C12 cells

Zhou, Bian-hua; Tan, Panpan; Jia, Liu-shu; Zhao, Wenpeng; Wang, Hongwei

doi:10.1016/j.chemosphere.2018.02.057

Cited by 46 publications

(18 citation statements)

References 41 publications

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“…Moreover, previous studies have confirmed that the PI3K/Akt signaling pathway can inhibit apoptosis in breast cancer by regulating the phosphorylation of Bad [44,45]. Cell death can be promoted through Bad binding with Bcl-2 but blocked by Bad phosphorylation [44,45]. In the current study, Rg5 reduced the phosphorylation of PI3K, Akt, mTOR, and Bad, which suggested that Rg5 suppressed the PI3K/Akt pathway in breast cancer cells.…”

Section: Discussionsupporting

confidence: 66%

“…A growing amount of evidence has clarified that mTOR is the center of autophagic regulatory cascades, which directly associate with the PI3K/Akt pathway in the autophagic pathway [42,43]. Moreover, previous studies have confirmed that the PI3K/Akt signaling pathway can inhibit apoptosis in breast cancer by regulating the phosphorylation of Bad [44,45]. Cell death can be promoted through Bad binding with Bcl-2 but blocked by Bad phosphorylation [44,45].…”

Section: Discussionmentioning

confidence: 99%

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The Preparation of Ginsenoside Rg5, Its Antitumor Activity against Breast Cancer Cells and Its Targeting of PI3K

Liu

Fan

2020

Nutrients

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Ginsenosides have been reported to possess various pharmacological effects, including anticancer effects. Nevertheless, there are few reports about the antitumor activity and mechanisms of ginsenoside Rg5 against breast cancer cells. In the present study, the major ginsenoside Rb1 was transformed into the rare ginsenoside Rg5 through enzymatic bioconversion and successive acid-assisted high temperature and pressure processing. Ginsenosides Rb1, Rg3, and Rg5 were investigated for their antitumor effects against five human cancer cell lines via the MTT assay. Among them, Rg5 exhibited the greatest cytotoxicity against breast cancer. Moreover, Rg5 remarkably suppressed breast cancer cell proliferation through mitochondria-mediated apoptosis and autophagic cell death. LC3B-GFP/Lysotracker and mRFP-EGFP-LC3B were utilized to show that Rg5 induced autophagosome-lysosome fusion. Western blot assays further illustrated that Rg5 decreased the phosphorylation levels of PI3K, Akt, mTOR, and Bad and suppressed the PI3K/Akt signaling pathway in breast cancer. Moreover, Rg5-induced apoptosis and autophagy could be dramatically strengthened by the PI3K/Akt inhibitor LY294002. Finally, a molecular docking study demonstrated that Rg5 could bind to the active pocket of PI3K. Collectively, our results revealed that Rg5 could be a potential therapeutic agent for breast cancer treatment.

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Section: Discussionsupporting

confidence: 66%

Section: Discussionmentioning

confidence: 99%

The Preparation of Ginsenoside Rg5, Its Antitumor Activity against Breast Cancer Cells and Its Targeting of PI3K

Liu

Fan

2020

Nutrients

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“…The Akt pathway plays a key role in cell proliferation, apoptosis, drug resistance and differentiation. 8 NFIB also has been reported to bind to the EZH2 promoter and promote EZH2 expression, 9 which can activate the PI3K/AKT pathway. 10 Wu et al 11 demonstrates that NFIB can activate the Akt/Stat3 signaling pathway.…”

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confidence: 99%

Nuclear factor I/B promotes colorectal cancer cell proliferation, epithelial‐mesenchymal transition and 5‐fluorouracil resistance

et al. 2018

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Nuclear factor I/B (NFIB) is a widely studied transcription factor that participates in tumor progression; nevertheless, studies on NFIB in colorectal cancer (CRC) are limited. In our study, Western blot and RT‐PCR analyses showed that NFIB was overexpressed in CRC tissues and cell lines, which was consistent with our bioinformatic analysis results. Furthermore, NFIB expression was closely related to the TNM stage of CRC. NFIB promoted cell proliferation and migration and inhibited cell apoptosis in vitro. Meanwhile, we discovered that NFIB accelerated xenograft tumor growth in vivo. In addition, NFIB weakened the sensitivity of CRC cells to 5‐fluorouracil (5‐FU). NFIB induced epithelial‐mesenchymal transition (EMT) by upregulating snail expression, which was accompanied by decreased E‐cadherin and Zo‐1 expression and increasedd Vimentin expression. Because the Akt pathway plays an important role in CRC progression, we examined whether there was a correlation between NFIB and the Akt pathway in cell proliferation and migration. Our results showed that NFIB promoted cell proliferation and increased 5‐FU resistance by activating the Akt pathway. In summary, our findings suggested that NFIB induced EMT of CRC cells via upregulating snail expression and promoted cell proliferation and 5‐FU resistance by activating the Akt pathway.

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“…The unique circRNAs that operate at the three functional transition periods in goat skeletal muscle may represent the beginning/termination of a certain physiological and/or growth process at a particular stage. For example, circPDGFC, circTTN, circITGA4, and circLPAR1 that are expressed in stage 1 (from F45 to F90) take part in the "PI3K-Akt signaling pathway", "regulation of actin cytoskeleton" and other processes that relate to muscle developmental, formation and structure [39][40][41]. Stage 2 circRNAs, operating from F90 to B1, are involved in acid metabolism and the attachment of the cytoplasmic surface to the actin cytoskeleton, including circACTN2, circMAPK1 and others.…”

Section: Discussionmentioning

confidence: 99%

Trend analysis of the role of circular RNA in goat skeletal muscle development

et al. 2020

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Background: Circular RNA (circRNA) is produced during the splicing of mRNA (in addition to linear splicing) and is part of the gene regulatory network. The temporal expression patterns the different developmental stages were inseparable from these molecules' function. Results: Skeletal muscles of Anhui white goat (AWG) across seven fetal to postnatal development stages were sequenced and 21 RNA sequencing libraries were constructed. We thereby identified 9090 circRNAs and analyzed their molecular properties, temporal expression patterns, and potential functions at the different stages. CircRNAs showed complexities and diversity of formation as the same host gene produces multiple isoforms of these nucleic acids with different expression profiles. The differential expression of 2881 circRNAs (DECs, P < 0.05) was identified and four were randomly selected and validated by qPCR. Moreover, 1118 DECs under strict selected (SDECs, |log2 FC | > 2 and P-adj value < 0.01) showed 4 expression trends (Clusters 0, 19, 16 and 18). Cluster 0 molecules had increasing expression at all stages with effects on muscle through metabolism, regulation of enzyme activity, and biosynthesis. Cluster 16 circRNAs had high expression in the early and late stages and are involved in "Wnt signaling pathway", "AMPK signaling pathway" and others. Cluster 18 molecules were mainly expressed at F120 and participate in "cytoskeletal protein binding", "Notch signaling pathway" and so on. Cluster 19 circRNAs were down-regulated at all stages and related to muscle structure and development. Lastly, the SDECs divided the period of skeletal muscle development into three transitional stages: stage 1 (F45 to F90), which related to muscle satellite cell proliferation and muscle fiber structure; stage 2 (F90 to B1), in which the attachment of the cytoplasmic surface to the actin cytoskeleton initiates; and stage 3, which involved the "cGMP-PKG signaling pathway". Moreover, the paraffin sections messages also validated that there are three transitional stages of skeletal muscle development. Conclusion: Our current study provides a catalog of goat muscle-related circRNAs that can stratify skeletal muscle development fetus 45 days to newborn 90 days into three developmental stages. These findings better our understanding of functional transitions during mammalian muscle development.

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PI3K/AKT signaling pathway involvement in fluoride-induced apoptosis in C2C12 cells

Cited by 46 publications

References 41 publications

The Preparation of Ginsenoside Rg5, Its Antitumor Activity against Breast Cancer Cells and Its Targeting of PI3K

The Preparation of Ginsenoside Rg5, Its Antitumor Activity against Breast Cancer Cells and Its Targeting of PI3K

Nuclear factor I/B promotes colorectal cancer cell proliferation, epithelial‐mesenchymal transition and 5‐fluorouracil resistance

Trend analysis of the role of circular RNA in goat skeletal muscle development

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PI3K/AKT signaling pathway involvement in fluoride-induced apoptosis in C2C12 cells

Cited by 46 publications

References 41 publications

The Preparation of Ginsenoside Rg5, Its Antitumor Activity against Breast Cancer Cells and Its Targeting of PI3K

The Preparation of Ginsenoside Rg5, Its Antitumor Activity against Breast Cancer Cells and Its Targeting of PI3K

Nuclear factor I/B promotes colorectal cancer cell proliferation, epithelial‐mesenchymal transition and 5‐fluorouracil resistance

Trend analysis of the role of circular RNA in goat skeletal muscle development

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PI3K/AKT signaling pathway involvement in fluoride-induced apoptosis in C2C12 cells