scholarly journals Tricholoma matsutake Aqueous Extract Induces Hepatocellular Carcinoma Cell Apoptosis via Caspase-Dependent Mitochondrial Pathway

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Yanzhen Wang ◽  
Yiling Chen ◽  
Xinrui Zhang ◽  
Guangsheng Cai ◽  
Shengshu An ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Aqueous Extract ◽  
Cell Apoptosis ◽  
B Cell Lymphoma ◽  
Mitochondrial Pathway ◽  
Tricholoma Matsutake ◽  
Migration Ability ◽  
Cytotoxicity Activities

Tricholoma matsutake, one of widely accepted functional mushrooms, possesses various pharmacological activities, and its antitumor effect has become an important research point. Our study aims to evaluate the cytotoxicity activities of T. matsutake aqueous extract (TM) in HepG2 and SMMC-7721 cells. In in vitro experiments, TM strikingly reduced cell viability, promoted cell apoptosis, inhibited cell migration ability, induced excessive generation of ROS, and caused caspases cascade and mitochondrial membrane potential dissipation in hepatocellular carcinoma cells. In in vivo experiments, 14-day TM treatment strongly suppressed tumor growth in HepG2 and SMMC-7721-xenografted nude mice without influence on their body weights and liver function. Furthermore, TM increased the levels of cleaved poly-ADP-ribose polymerase (PARP), Bad, and Bax and reduced the expressions of B-cell lymphoma 2 (Bcl-2) in treated cells and tumor tissues. All aforementioned results suggest that caspase-dependent mitochondrial apoptotic pathways are involved in TM-mediated antihepatocellular carcinoma.

scholarly journals Huxie Huaji Ointment Induced Apoptosis of Liver Cancer Cells In Vivo and In Vitro by Activating the Mitochondrial Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Yuan Cai ◽  
Qing Du ◽  
Tian-Hao Deng ◽  
Bing-Bing Shen ◽  
Yan-Mei Peng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Suppressor ◽  
Hepg2 Cell ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
B Cell Lymphoma ◽  
Cell Counting ◽  
Cyt C

Huxie Huaji (HXHJ) Ointment is a famous traditional Chinese medicinal prescription and is commonly used for the clinical treatment of hepatocellular carcinoma by boosting immunity and detoxification. However, the scientific evidence for the effect of HXHJ Ointment on hepatocellular carcinoma and the underlying molecular mechanism are lacking. The present study aimed to identify the effects of HXHJ Ointment on hepatocellular carcinoma in vitro and in vivo as well as investigating the mechanistic basis for the anticancer effect of HXHJ ointment. First, liquid chromatography-mass spectrometry was used to verify the composition of HXHJ Ointment and quality control. Second, in vitro, Cell Counting Kit (CCK8) cell viability assay and Hoechst 33342 staining assay were performed to explain the cell apoptosis. The protein levels of tumor suppressor protein (p53), B-cell lymphoma 2 gene (Bcl-2), cytochrome C (Cyt-C), and aspartate proteolytic enzyme-3 (caspase-3) were examined by immunofluorescence. Finally, in vivo, hematoxylin and eosin (H&E) staining was used to observe the pathological changes in hepatocellular carcinoma samples. Western blots and immunohistochemistry were used to detect the anticancer properties of HXHJ ointment. The results in vitro showed that 20% HXHJ Ointment serum could significantly inhibit HepG2 cell proliferation, increased tumor suppressor gene p53, downregulated antiapoptotic protein Bcl-2, promoted the release of mitochondrial Cyt-C, activated caspase-3, and induced HepG2 cell apoptosis. Furthermore, in vivo experiments showed that HXHJ Ointment could effectively inhibit tumor growth in nude mice xenotransplanted with HepG2 cells, changed the morphology of tumor cells, and regulated the expression of apoptosis-related protein pathway p53/Bcl-2/Cyt-C/caspase-3. HXHJ Ointment can significantly inhibit the development of hepatocellular carcinoma, and its mechanism may be related to the regulation of p53/Bcl-2/Cyt-C/caspase-3 signaling pathway to induce cell mitochondrial apoptosis.

scholarly journals Histone methyltransferase WHSC1 inhibits colorectal cancer cell apoptosis via targeting anti-apoptotic BCL2

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yu Wang ◽  
Liming Zhu ◽  
Mei Guo ◽  
Gang Sun ◽  
Kun Zhou ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cell ◽  
Cell Apoptosis ◽  
B Cell Lymphoma ◽  
Histone Methyltransferase ◽  
Chemotherapeutic Agents ◽  
Cancer Cell Apoptosis ◽  
Active Transcription

AbstractWHSC1 is a histone methyltransferase that facilitates histone H3 lysine 36 dimethylation (H3K36me2), which is a permissive mark associated with active transcription. In this study, we revealed how WHSC1 regulates tumorigenesis and chemosensitivity of colorectal cancer (CRC). Our data showed that WHSC1 as well as H3K36me2 were highly expressed in clinical CRC samples, and high WHSC1 expression is associated with poorer prognosis in CRC patients. WHSC1 reduction promoted colon cancer cell apoptosis both in vivo and in vitro. We found that B cell lymphoma-2 (BCL2) expression, an anti-apoptotic protein, is markedly decreased in after WHSC1 depletion. Mechanistic characterization indicated that WHSC1 directly binds to the promoter region of BCL2 gene and regulate its H3K36 dimethylation level. What’s more, our study indicated that WHSC1 depletion promotes chemosensitivity in CRC cells. Together, our results suggested that WHSC1 and H3K36me2 modification might be optimal therapeutic targets to disrupt CRC progression and WHSC1-targeted therapy might potentially overcome the resistance of chemotherapeutic agents.

1,2-Dichloroethane induces cerebellum granular cell apoptosis via mitochondrial pathway in vitro and in vivo

2020 ◽  
Vol 322 ◽  
pp. 87-97 ◽  
Author(s):  
Manqi Huang ◽  
Yizhou Zhong ◽  
Li Lin ◽  
Boxuan Liang ◽  
Jun Liu ◽  
...  
Keyword(s):  
Cell Apoptosis ◽  
Granular Cell ◽  
Mitochondrial Pathway

scholarly journals Anticancer Effects of Cyclocarya paliurus Polysaccharide (CPP) on Thyroid Carcinoma In Vitro and In Vivo

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Zhiwei He ◽  
Fangfang Lv ◽  
Yueli Gan ◽  
Jing Gu ◽  
Ting Que
Keyword(s):  
Thyroid Cancer ◽  
Cancer Cell ◽  
Western Blotting ◽  
Cell Apoptosis ◽  
Cancer Cell Line ◽  
B Cell Lymphoma ◽  
Thyroid Cancer Cell ◽  
Cyclocarya Paliurus

In this study, we explored the role and mechanisms of Cyclocarya paliurus polysaccharide on cell apoptosis in thyroid cancer (TC) cells. The apoptosis of thyroid cancer cells in vitro and tumor tissues in vivo induced by Cyclocarya paliurus polysaccharide was determined by MTT assay and flow cytometric assay. The downstream molecules including phosphop-protein kinase B (p-Akt), Akt, B-cell lymphoma 2 (Bcl-2), and Bcl-2-associated X protein (Bax) in tumor tissue were evaluated by western blotting. MTT and flow cytometry assay in vitro revealed Cyclocarya paliurus polysaccharide-induced apoptosis of thyroid cancer cell line in a manner of time-dependent and dose-dependent. In vivo assay showed 50 mg/kg and 100 mg/kg Cyclocarya paliurus polysaccharide significantly suppressed the proliferation of thyroid cancer in mice. Western blotting showed downregulation of p-Akt, Akt, and Bcl-2 and upregulation of Bax. These results suggest that Cyclocarya paliurus polysaccharide may enhance thyroid cancer cell apoptosis by suppressing the activation of p-Akt, Akt, and Bcl-2 and activating Bax, which provide a novel use of CPP as a thyroid cancer treatment.

A cytotoxic nitrido-osmium(vi) complex induces caspase-mediated apoptosis in HepG2 cancer cells

2020 ◽  
Vol 49 (47) ◽  
pp. 17173-17182
Author(s):  
Wan-Qiong Huang ◽  
Chuan-Xian Wang ◽  
Tao Liu ◽  
Zi-Xin Li ◽  
Chen Pan ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Hepg2 Cell ◽  
Cell Apoptosis ◽  
Death Receptor ◽  
Mitochondrial Pathway ◽  
Anticancer Activities ◽  
Death Receptor Pathway

A structurally fine-tuned nitridoosmium(vi) complex induces HepG2 cell apoptosis through activation of the mitochondrial pathway and death receptor pathway, showing promising in vitro and in vivo anticancer activities.

scholarly journals Fasting Induces Hepatocellular Carcinoma Cell Apoptosis by Inhibiting SET8 Expression

2020 ◽  
Vol 2020 ◽  
pp. 1-19 ◽  
Author(s):  
Jie Qi ◽  
Xiangyuan Chen ◽  
Qichao Wu ◽  
Jing Wang ◽  
Hao Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Viability ◽  
Cell Apoptosis ◽  
Antioxidant Response ◽  
Signalling Pathway ◽  
Related Factor ◽  
Apoptosis Resistance ◽  
Cancer Proliferation

Background. Hepatocellular carcinoma (HCC) is a life-threatening cancer, and the Kelch-like ECH-associated protein 1 (Keap1)/NF-E2-related factor 2 (Nrf2)/antioxidant response element (ARE) signalling pathway plays a crucial role in apoptosis resistance in cancer cells. Fasting is reported to mediate tumour growth reduction and apoptosis. SET8 is involved in cancer proliferation, invasiveness, and migration. However, whether SET8 participates in fasting-mediated apoptosis in HCC remains unclear. Methods. We used immunohistochemical staining to analyse the expression of SET8, Keap1, and Nrf2 in HCC tissues. Cell viability, apoptosis, and cellular reactive oxygen species (ROS) were assessed, and Western blot and qPCR analyses were used to examine the expression of Keap1/Nrf2 in HCC cells under fasting, SET8 overexpression, and PGC1α overexpression conditions. Mass spectrometry, coimmunoprecipitation, and confocal microscopy were used to determine whether PGC1α interacts with SET8. In vivo experiments were performed to verify the conclusions from the in vitro experiments. Results. Our data indicate that SET8 expression is associated with poor survival in HCC patients. Both in vitro and in vivo results demonstrated that fasting decreased cell viability and downregulated expression of SET8, Nrf2, and downstream effectors of Nrf2, while it upregulated Keap1 expression, mediated ROS accumulation, and induced HCC cell apoptosis. These results were similar to what is observed in SET8-deficient cells. Furthermore, SET8 was found to interact with PGC1α, and both PGC1α and H4K20me1, a downstream target of SET8, were found to be enriched at the Keap1 promoter region. These two factors were further determined to attenuate Keap1 promoter activity. Conclusions. The results of our study demonstrate that fasting induces HCC apoptosis by inhibiting SET8 expression and that SET8 interacts with PGC1α to activate the Nrf2/ARE signalling pathway by inhibiting Keap1 expression.

Bone mesenchymal stem cells derived extracellular vesicles promotes TRAIL-related apoptosis of hepatocellular carcinoma cells via the delivery of microRNA-20a-3p

2020 ◽  
pp. 1-13
Author(s):  
Lu Deng ◽  
Chang Wang ◽  
Chao He ◽  
Li Chen
Keyword(s):  
Hepatocellular Carcinoma ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Conditioned Medium ◽  
Extracellular Vesicles ◽  
Cell Apoptosis ◽  
Bone Mesenchymal Stem Cells ◽  
Hcc Cells

OBJECTIVE: Bone mesenchymal stem cells (BMSCs) have been widely researched in cancer treatment, including hepatocellular carcinoma (HCC). This study intended to discuss the mechanism of miR-20a-3p in BMSCs-extracellular vesicles (EVs) in HCC apoptosis. METHODS: BMSCs were isolated and identified. EVs derived from BMSCs were extracted and identified. After overexpressing or inhibiting miR-20a-3p expression in BMSCs, EVs were extracted and acted on HCC cells and transplanted tumors. HCC cell apoptosis in the treatment of BMSCs-conditioned medium, BMSCs-EVs and/or miR-20a-3p mimic/inhibitor were evaluated, with the detection of levels of TRAIL and TRAIL-related proteins. A functional rescue experiment about c-FLIP was carried out in HCC cells. The target binding relationship between miR-20a-3p and c-FLIP was detected. The subcutaneous tumorigenesis model of mice was established and injected with BMSCs-EVs to estimate the effect of BMSCs-EVs-miR-20a-3p on HCC growth. RESULTS: EVs isolated from BMSCs conditioned medium promoted the apoptosis of HCC cells. After BMSCs-EVs treatment, TRAIL levels, downstream proteins and miR-20a-3p were increased significantly, but the expression of c-FLIP was decreased. miR-20a-3p could target c-FLIP. BMSCs-EVs inhibited the growth of HCC cells, decreased c-FLIP expression, increased TRAIL levels, and promote the of HCC cell apoptosis. BMSCs-EVs with overexpressing miR-20a-3p further enhanced the apoptotic effect of HCC cells in vitro and in vivo. CONCLUSION: BMSCs-EVs-carried miR-20a-3p targets c-FLIP and increases TRAIL levels in HCC cells, thus promoting TRAIL-related apoptosis.

CISSAMPELOS PAREIRA: PROTEIN-LIGAND DOCKING TO IDENTIFY SUITABLE TARGETS FOR HEPATOCELLULAR CARCINOMA (HCC) BY IN-SILICO TECHNIQUES AND TOOLS

2015 ◽  
Vol 77 (2) ◽  
Author(s):  
B. Samuel Thavamani ◽  
Molly Mathew ◽  
Dhanabal S. Palaniswamy
Keyword(s):  
Hepatocellular Carcinoma ◽  
Growth Factor ◽  
In Silico ◽  
B Cell Lymphoma ◽  
Aurora Kinase ◽  
Pharmacological Action ◽  
Ligand Docking ◽  
Ligand Interaction

Protein-ligand interaction plays a major role in identification of the possible mechanism by which a ligand can bind with the target and exerts the pharmacological action. The present study aims to identify new possible candidates for treating Hepatocellular Carcinoma (HCC) by docking the reported phytochemicals present in Cissampelos pareira with the well known HCC targets using in-silico techniques. Although C. pareira demonstrated in vitro and in vivo anti-heptatocellular carcinoma activities, the mechanism remains uncertain. Selected compounds from C. pareira were docked using GLIDE software with known targets of hepatocellular carcinoma viz. Aurora Kinase, c-Kit, Fibroblast Growth Factor (FGF), Nuclear Factor kappa B (NF-kB), B-cell lymphoma-extra large (Bcl-xL) and Vascular Endothelial Growth Factor (VEGF). Among the compounds docked, pareitropone and pareirubrine B exhibited good hydrogen bonding interactions and binding energy with the targets of HCC taken in the study. Hence these compounds deserve consideration for further studies towards HCC.

scholarly journals Silencing of KNTC1 inhibits hepatocellular carcinoma cells progression via suppressing PI3K/Akt pathway

2020 ◽  
Author(s):  
Hui Tong ◽  
Junjie Xie ◽  
Xiaohui Liu ◽  
Chenghong Peng ◽  
Baiyong Shen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Regression ◽  
Annexin V ◽  
Tumor Formation ◽  
Migration Ability ◽  
Migration Assay ◽  
In Vivo Experiments ◽  
Hcc Cells

Abstract Background: Kinetochore associated 1 (KNTC1) encodes a kinetochore component in Rod-Zwilch-ZW10 (RZZ) complex which is essential for the segregation of sister chromatids during mitosis and participates in the spindle checkpoint. Recent research demonstrated that kinetochore proteins may be potential biomarkers and may contribute to the development of human malignancies. Here, we sought to identify the biological significances of KNTC1 in hepatocellular carcinoma (HCC).Methods: KNTC1 expression was studied in HCC tissues by immunohistochemistry. Lentivirus delivered short hairpin RNA (shRNA) was performed to generate KNTC1 knockdown HCC cell lines. The effects of KNTC1 on HCC cells proliferation, migration, apoptosis and tumor formation was analyzed by MTT assay, colony formation assay, wound-healing assay, transwell migration assay, annexin V assay in vitro and in nude mouse models in vivo.Results: Our immunohistochemistry experiment showed that KNTC1 was highly expressed in HCC tissues and correlated with terrible prognosis, indicating that KNTC1 acts a pivotal role in HCC development. Furthermore, shRNA KNTC1 (Lv‑shKNTC1) was applied to infect BEL-7404 and SK-HEP-1 to identify roles of KNTC1 on HCC. Lv‑shKNTC1 cells showed reduced proliferation ability, increased apoptosis and decreased migration ability. In vivo experiments suggested that xenografts grow significantly slower upon the silencing of KNTC1. Mechanistically, the protein levels of PIK3CA, p-Akt, CCND1, CDK6 are all down-regulated in Lv-KNTC1 SK-HEP-1 cells. Therefore, KNTC1 may affect the biological activity of HCC cells through PI3K/Akt signaling pathway. Conclusions: In summary, the key finding of this report highlighted the significance of KNTC1 in tumor regression of HCC, demonstrating KNTC1 as an innovative target for adjuvant treatment of HCC.

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