Genistein Enhances Radiosensitivity of Human Hepatocellular Carcinoma Cells by Inducing G2/M Arrest and Apoptosis

Yan, Hongli; Jiang, Jing; Du, Aiying; Gao, Jinli; Zhang, Daisong; Liu, Song

doi:10.1667/rr15380.1

Cited by 23 publications

(14 citation statements)

References 49 publications

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“…The DEVD motif of PARP is recognized by caspase proteases and cleaved into two fragments (P89 and P24), thus resulting in its inactivation (56). When cellular DNA is damaged, the cell cycle normally arrests in the G2/M phase to allow repair; if the damage is irreparable, the apoptotic pathway can be activated (57). In the present study, the expression of PARP in GCs was significantly reduced in the BHBA-2.4 mM group; in addition, GCs were blocked in the G2/M phase.…”

Section: Discussionmentioning

confidence: 99%

The Dynamic Transcription Profiles of Proliferating Bovine Ovarian Granulosa When Exposed to Increased Levels of β-Hydroxybutyric Acid

et al. 2022

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Ketosis is common in high-yield dairy cows. It is a condition that is characterized by the accumulation of serum β-hydroxybutyric acid (BHBA). Both subclinical ketosis and clinical ketosis can compromise the reproductive performance and cause long-lasting negative effects on reproductive efficiency by affecting the proliferation of follicular and granulosa cells. However, the regulatory mechanisms involved in the development of follicular cells and granulosa cells in cows experiencing subclinical ketosis and clinical ketosis remain largely unknown. To investigate the effect of a ketosis-triggered increase in BHBA on bovine follicular granulosa cell development, we detected a significant reduction in the proliferation of granulosa cells (P < 0.05) in the BHBA-1.2 mM and BHBA-2.4 mM groups and a significant increase in the number of granulosa cells in the G1 phase of the cell cycle (P < 0.05). RNA-seq and trend analysis were used to identify differentially expressed genes by comparing three clusters: low-concentration response to 1.2 mM BHBA, high-concentration response to 2.4 mM BHBA, and the similar trend (up or down) response following BHBA concentration increased. GO and KEGG enrichment analyses were performed separately for each cluster. Analysis showed that two novel down-regulated genes (G0S2 and S100A6), which are associated with cell proliferation and cycle progression, were enriched in the low-concentration response to 1.2 mM BHBA. Another differentially expressed gene (PARP), which plays a role in the apoptotic pathway, was enriched in the high-concentration response to 2.4 mM BHBA. We also found that CYP27B1 and CYP17A1, which are associated with Ca2+ homeostasis and estrogen synthesis, were enriched in a similar trend response. In conclusion, we describe the dynamic transcription profiles of granulosa cells under different levels of β-hydroxybutyric stress and report key regulators that may underlie the detrimental effects on the development of follicles and granulosa cells, thus representing potential therapeutic targets to improve fertility in dairy cows with subclinical ketosis or clinical ketosis.

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Section: Discussionmentioning

confidence: 99%

The Dynamic Transcription Profiles of Proliferating Bovine Ovarian Granulosa When Exposed to Increased Levels of β-Hydroxybutyric Acid

et al. 2022

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“…Similarly, comparative to breast cancer malignant cells (MDA-MB-231), genistein treatment down-regulated p21WAF1 expression in normal breast epithelial cells (MCF10A and MCF12A), suggesting cancer cell specific cytotoxic effect of genistein [ 43 ]. In hepatic cellular carcinoma HepG2, Huh7 and Hep3B cell lines, pro-apoptotic influence of genistein was reported to be more pronounced than normal hepatic L-02 cells [ 44 ]. Likewise, chitosan-encapsulated genistein treatment in colon cancer HT-129 cells promoted anti-angiogenesis while the viability of normal cells was not effected in tested genistein concentrations [ 45 ].…”

Section: Introductionmentioning

confidence: 99%

Genistein as a regulator of signaling pathways and microRNAs in different types of cancers

et al. 2021

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Cancers are complex diseases orchestrated by a plethora of extrinsic and intrinsic factors. Research spanning over several decades has provided better understanding of complex molecular interactions responsible for the multifaceted nature of cancer. Recent advances in the field of next generation sequencing and functional genomics have brought us closer towards unravelling the complexities of tumor microenvironment (tumor heterogeneity) and deregulated signaling cascades responsible for proliferation and survival of tumor cells. Phytochemicals have begun to emerge as potent beneficial substances aimed to target deregulated signaling pathways. Isoflavonoid genistein is an essential phytochemical involved in regulation of key biological processes including those in different types of cancer. Emerging preclinical evidence have shown its anti-cancer, anti-inflammatory and anti-oxidant properties. Testing of this substance is in various phases of clinical trials. Comprehensive preclinical and clinical trials data is providing insight on genistein as a modulator of various signaling pathways both at transcription and translation levels. In this review we have explained the mechanistic regulation of several key cellular pathways by genistein. We have also addressed in detail various microRNAs regulated by genistein in different types of cancer. Moreover, application of nano-formulations to increase the efficiency of genistein is also discussed. Understanding the pleiotropic potential of genistein to regulate key cellular pathways and development of efficient drug delivery system will bring us a step towards designing better chemotherapeutics.

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“…Numerous studies have shown that the radiosensitivity of tumour cells is associated with apoptosis [29] and that induction of apoptosis can enhance the radiosensitivity of cancer cells. Loss of cyclin G1 can induce apoptosis in uterine leiomyoma cells [30].…”

Section: Discussionmentioning

confidence: 99%

Silencing the Expression of Cyclin G1 Enhances the Radiosensitivity of Hepatocellular Carcinoma In Vitro and In Vivo by Inducing Apoptosis

Wang

et al. 2021

Radiation Research

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Background: Radiotherapy plays an important role in the treatment of hepatocellular carcinoma (HCC).Cyclin G1 was a novel member of the cyclin family, and it is abnormally expressed in HCC. The aim of this study was to investigate the role of cyclin G1 in the radiotherapy of HCC cells.Methods: The expression of cyclin G1 was silenced by transfection of cyclin G1-siRNA into HepG2 cells, and the expression of cyclin G1 mRNA and protein was measured by qRT-PCR and western blot analysis.The proliferation was analysed by MTT assay, and the radiosensitivity of HCC cells was detected by using a colony formation assay and a xenograft tumour model. The expression of apoptosis-related proteins (Bcl-2 and Bax) was detected by western blot analysis.Results: The expression of cyclin G1 mRNA and protein in HepG2-cyclin G1-siRNA cells is signi cantly decreased compared with that in HepG2 cells. Silencing the expression of cyclin G1 inhibits the proliferation of HCC cells and enhances the radiosensitivity of HepG2 cells in vitro and in vivo. HepG2cyclin G1-siRNA signi cantly decreases Bcl-2 expression and increases Bax expression in cells. Conclusion:Silencing the expression of cyclin G1 enhances the radiosensitivity of HCC cells in vitro and in vivo, and the mechanism is probably related to the regulation of apoptosis-related proteins.

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Genistein Enhances Radiosensitivity of Human Hepatocellular Carcinoma Cells by Inducing G2/M Arrest and Apoptosis

Cited by 23 publications

References 49 publications

The Dynamic Transcription Profiles of Proliferating Bovine Ovarian Granulosa When Exposed to Increased Levels of β-Hydroxybutyric Acid

The Dynamic Transcription Profiles of Proliferating Bovine Ovarian Granulosa When Exposed to Increased Levels of β-Hydroxybutyric Acid

Genistein as a regulator of signaling pathways and microRNAs in different types of cancers

Silencing the Expression of Cyclin G1 Enhances the Radiosensitivity of Hepatocellular Carcinoma In Vitro and In Vivo by Inducing Apoptosis

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