Aloperine induces apoptosis and G2/M cell cycle arrest in hepatocellular carcinoma cells through the PI3K/Akt signaling pathway

Liu, Junshan; Huo, Chuying; Cao, Hongxin; Fan, Chun‐Lin; Hu, Jiaxing; Deng, Lijuan; Lu, Zibin; Yang, Huayi; Yu, Linzhong; Mo, Zhixian; Yu, Zhi‐Ling

doi:10.1016/j.phymed.2019.152843

Cited by 98 publications

(64 citation statements)

References 24 publications

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“…Regarding the PI3K-Akt signaling pathway, numerous studies have also reported its crucial role in the process of HCC. The PI3K-Akt signaling pathway has been widely reported to act as a key factor related to cell proliferation, invasion, metastasis, and apoptosis as well as the cell cycle [52][53][54][55][56]. Given that, we speculated that the molecular mechanism of CELSR3 in promoting cell proliferation, invasion, and migration, as well as inhibiting apoptosis may be closely associated with the cell cycle, DNA replication, and the PI3K-Akt signaling pathway through interacting with its co-expressed genes.…”

Section: Discussionmentioning

confidence: 93%

Effect of CELSR3 on the Cell Cycle and Apoptosis of Hepatocellular Carcinoma Cells

Xie

Dang

et al. 2020

J. Cancer

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Cadherin EGF LAG seven-pass G-type receptor 3 (CELSR3) has been reported in cancers but its role and potential molecular mechanism in hepatocellular carcinoma (HCC) is unclear. Therefore, we aimed to investigate the clinical value and molecular mechanism of CELSR3 in HCC using an in vitro experiment, a meta-analysis and bioinformatics. The in vitro experiment determined the promoting effect of CELSR3 in the proliferation, invasion, and migration of HCC cells. CELSR3 knockout causes S-phage arrest in HCC cells. CELSR3 can also inhibit the apoptosis of HCC cells. The expression of the CELSR3 gene and protein was significantly elevated in HCC. Elevated CELSR3 was correlated to the bigger tumor size, higher pathological stage, and the worse overall survival of HCC. Methylation analysis revealed that the hypomethylation of CELSR3 regulated by DNMT1, DNMT3A, and DNMT3B may be the underlying mechanism of upregulated CELSR3. Biological enrichment analysis uncovered that the cell cycle, DNA replication, and PI3K-Akt signaling pathways were important pathways regulated by CELSR3 and its co-expressed genes in HCC. Taken together, upregulated CELSR3 is an important regulator in the progression and prognosis of HCC. The hypomethylation of CELSR3 and its regulation in the cell cycle may be the potential molecular mechanism in HCC.

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Section: Discussionmentioning

confidence: 93%

Effect of CELSR3 on the Cell Cycle and Apoptosis of Hepatocellular Carcinoma Cells

Xie

Dang

et al. 2020

J. Cancer

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“…Apoptosis is an essential cell process in the homeostasis of multicellular organisms, and its dysregulation has been involved in many human tumors [39,40]. G2/M phase cell cycle arrest is one of the most prominent checkpoints of many anticancer agents which can reduce proliferation and then induce apoptosis by inhibiting the segregation of damaged chromosomes during mitosis [41][42][43]. Cell migration is implicated in various processes including embryogenesis, tissue regeneration, wound healing, and tumor progression.…”

Section: Discussionmentioning

confidence: 99%

Bidirect effects from cisplatin combine with rosmarinic acid (RA) or hot water extracts of Glechoma hederacea (HWG) on renal cancer cells

Chou

Tai

et al. 2020

Preprint

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Background: Cisplatin (CDDP) is a chemotherapeutic drug which also causes adverse side effects.Glechoma hederacea is a traditional Chinese herb belonging to the Labiatae family and has many biological activities. Our previous study indicated that rosmarinic acid (RA) was the most abundant phytochemical in G. hederacea. However, the antioxidant or anti-inflammatory effects of the combined treatment of G. hederacea, RA and CDDP on human renal cell carcinoma (RCC) 786-O cells have not been clearly demonstrated. We aimed to investigate the bioefficacy of hot water extracts of G. hederacea (HWG) and RA in inhibiting RCC 786-O cell activity and its synergism with CDDP against metastatic renal cancer cell. Methods:Bioactivities of the combination treatment of HWG, RA, HWG/CDDP and RA/CDDP were assessed using the MTT assay and transwell migration, and the crude extract/compound efficacy was evaluated using wound healing migration assays, flow cytometry and western blotting. Results: Our study indicates that CDDP inhibits 786-O cell proliferation and migration and HWG and RA protect against these effects. On the other hand, HWG and RA demonstrate a low cytotoxic effect in human renal proximal tubular epithelial cell line -2 (HK-2 cells). Cell cycle analysis found that HWG/CDDP and RA/CDDP combination treatment exerted cytotoxicity by inducing G2/M arrest and apoptosis. RA in combination with CDDP significantly inhibit the expression of p-FAK (Tyr 925) in RCC 786-O cells in vitro. Conclusion: We propose that the inhibition of RA on RCC 786-O cell invasion and migration may partly occur through the downregulation of FAK phosphorylation. The HWG/CDDP and RA/CDDP combination treatments may be effective strategies for intervention of RCC 786-O cell activity. BackgroundRenal cell carcinoma (RCC) is the most common type of kidney malignancy and accounts for ~ 3% of tumors in adults. However, only 2% RCC cases are associated with inherited gene mutations. It is also associated with a high metastatic potential [1,2]. RCC is the most lethal genitourinary cancer and patients with metastatic RCC have poor overall survival profiles [3]. 7075% renal cancers are clear cell carcinomas, which have traditionally been resistant to chemo-or radiotherapy [4]. One of the

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“…The PI3K-Akt signaling pathway, involving the key proteins phosphatidylinositol 3-kinase (PI3K) and Akt/Protein Kinase B, is an intracellular signal transduction road that promotes metabolism, hyperplasia, cell survival, growth and angiogenesis through responsing to extracellular signals. Dysregulation of the PI3K/Akt pathway is implicated in a number of human cancers [64][65][66][67].…”

Section: Discussionmentioning

confidence: 99%

Potential Therapeutic Value of Mangiferin for Lung Adenocarcinoma (Luad): A Comprehensive Study Based on in Vitro Experiments and Bioinformatics

Liu

Chi

Meng

et al. 2020

Preprint

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Background: Lung adenocarcinoma (LUAD), which is the most common lung cancer type in never-smokers and primarily occurs in women, requires effective treatment methods. Mangiferin is a polyphenol widely found in mango trees and has been reported to have chemotherapeutic and preventive potential against various types of cancer. Thus, we investigated the potential therapeutic value of mangiferin for LUAD.Methods: Cell lines A549, H2030 and H1299 were processed with mangiferin to detect and screen for differentially expressed lncRNAs and mRNAs. Close associations between extracted common lncRNAs and mRNAs were identified for lncRNA-mRNA network construction. Based on the network and an online database, target lncRNAs, target genes and meaningful lncRNA-mRNA pairs were identified, and signaling pathway analysis was performed.Results: The top 200 lncRNA-mRNA pairs were used to construct the network. We identified 12 target lncRNAs and 18 target genes. Gene nodes in the network were mostly visualized on the PI3K-Akt signaling pathway (P < 0.01). Furthermore, lncRNA-mRNA pairs that contained the genes ARHGAP29, BRIX1, CD109, CDK1, CTNNAL1, DAB2IP, DDIT4L, GPR162, ICAM5, KCNAB3 and MMP7 were considered to be meaningful lncRNA-mRNA pairs affected by mangiferin in LUAD.Conclusions: Our study provided a comprehensive understanding of the potential therapeutic value of mangiferin for LUAD.

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Aloperine induces apoptosis and G2/M cell cycle arrest in hepatocellular carcinoma cells through the PI3K/Akt signaling pathway

Cited by 98 publications

References 24 publications

Effect of CELSR3 on the Cell Cycle and Apoptosis of Hepatocellular Carcinoma Cells

Effect of CELSR3 on the Cell Cycle and Apoptosis of Hepatocellular Carcinoma Cells

Bidirect effects from cisplatin combine with rosmarinic acid (RA) or hot water extracts of Glechoma hederacea (HWG) on renal cancer cells

Potential Therapeutic Value of Mangiferin for Lung Adenocarcinoma (Luad): A Comprehensive Study Based on in Vitro Experiments and Bioinformatics

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