scholarly journals Davidone C Induces the Death of Hepatocellular Carcinoma Cells by Promoting Apoptosis and Autophagy

Molecules ◽  
2021 ◽  
Vol 26 (17) ◽  
pp. 5219
Author(s):  
Ping Song ◽  
Huiqi Huang ◽  
Yuanren Ma ◽  
Chaoqun Wu ◽  
Xinzhou Yang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Morphological Changes ◽  
Morphological Observation ◽  
Flavonoid Compound ◽  
Dependent Manner ◽  
Apoptotic Pathway ◽  
Mtt Method ◽  
Caspase 7 ◽  
Sophora Davidii ◽  
Apoptotic Mechanism

Davidone C is a newly discovered flavonoid compound purified from the ethyl acetate-soluble fraction of Sophora davidii (Franch.) Skeels. This study explored the anti-tumor activity of davidone C on hepatocellular carcinoma HepG2 and Bel-7402 cells and its mechanism through MTT method, morphological observation, flow cytometry and Western blotting. The results showed that davidone C significantly inhibited the proliferation of HepG2 and Bel-7402 cells in a time- and dose-dependent manner. The morphological changes of apoptotic cells can be observed under an inverted microscope, such as cell floating, chromosome condensation, apoptotic bodies, and other phenomena. The expressions of Bax, cleaved caspase-9, cleaved caspase-3 and cleaved PARP increased with the increase of dosage while Bcl-2 decreased, suggesting that the apoptotic mechanism might be related to the mitochondrial apoptotic pathway. Moreover, davidone C administration can down-regulate the expression of Grp78, and simultaneously up-regulate the expression of caspase-7 and caspase-12, indicating that the apoptotic mechanism might be related to the ERS pathway. In addition, davidone C can down-regulate the expression of p62, and simultaneously up-regulate the expression of LC3-I and LC3-II with a quantitative dependence, suggesting that the mechanism of apoptosis may be related to the autophagy signal pathway. All these results showed davidone C has potential effects on hepatocellular carcinoma.

scholarly journals Aspernolide A Inhibits the Proliferation of Human Laryngeal Carcinoma Cells through the Mitochondrial Apoptotic and STAT3 Signaling Pathways

Molecules ◽  
2019 ◽  
Vol 24 (6) ◽  
pp. 1074 ◽  
Author(s):  
Chang Liu ◽  
Hong Liu ◽  
Yanzhang Wen ◽  
Huiqi Huang ◽  
Ji Hao ◽  
...  
Keyword(s):  
Morphological Changes ◽  
Chromatin Condensation ◽  
Morphological Observation ◽  
Caspase 9 ◽  
Apoptotic Pathway ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Diphenyltetrazolium Bromide ◽  
Human Laryngeal Carcinoma ◽  
Apoptotic Mechanism

Aspernolide A, a butyrolactone secondary metabolite, was purified from the endophytic fungus Cladosporium cladosporioides derived from roots of Camptotheca acuminata Decne. In this study, the antitumor activity and mechanisms of aspernolide A on human laryngeal cancer Hep-2 and TU212 cells were studied by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, morphological observation and Western blotting. The results showed that aspernolide A significantly inhibited the proliferation of Hep-2 and TU212 cells in dose- and time-dependent manners. Morphological changes of apoptotic cells could be observed under an inverted microscope, such as irregular margins, decreased adherence ability and chromatin condensation. The expressions of Bax, Caspase-9, Caspase-3 and PARP (poly ADP-ribose polymerase) increased with the increase of dosage while Bcl-2 decreased, suggesting that the apoptotic mechanism might be related to the mitochondrial apoptotic pathway. Moreover, the expression of the phosphorylation of STAT3 decreased with the increase of dosage, suggesting that the apoptotic mechanism might be related to the STAT3 signaling pathway. All these conclusions indicated that aspernolide A has the potential anti-laryngocarcinoma effects.

scholarly journals Anticarcinogenic effect of indole-3-carbinol (I3C) on human hepatocellular carcinoma SNU449 cells

2018 ◽  
Vol 38 (1) ◽  
pp. 136-147 ◽  
Author(s):  
CM Lee ◽  
S-H Park ◽  
MJ Nam
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Human Hepatocellular Carcinoma ◽  
Time Dependent ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Dependent Manner ◽  
Caspase 7 ◽  
Thioredoxin 1 ◽  
Induced Apoptosis ◽  
Apoptotic Effects

Many cruciferous vegetables, including cabbage, contain indole-3-carbinol (I3C), which is a known anticarcinogen. However, the anticarcinogenic effects of I3C on liver cancer have not been investigated. Therefore, this study was conducted to evaluate the anticarcinogenic effects of I3C in human hepatocellular carcinoma (HCC) SNU449 cells. The results of MTT and WST-1 assays indicated that treatment of SNU449 cells with I3C decreased viability in dose- and time-dependent manners, while colony formation assays indicated that I3C also inhibited proliferation of SNU449 cells. Moreover, fluorescence-activated cell sorter analysis showed that I3C induced apoptosis in SNU449 cells in dose- and time-dependent manners. Furthermore, terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling revealed that I3C induced DNA fragmentation in SNU449 cells in a time-dependent manner, while Western blotting showed that apoptotic proteins such as p53, cleaved PARP, caspase-3, and caspase-7 were activated in SNU449 cells following treatment with I3C. Finally, reactive oxygen species-related protein peroxiredoxin-1 and thioredoxin-1 expression decreased in I3C-treated SNU449 cells. The aim of our study is to investigate the unknown mechanisms responsible for the apoptotic effects of I3C on human HCC SNU449 cells, and the results suggest that I3C may be useful for the prevention and treatment of liver cancer.

scholarly journals Responses of Bloom-Forming Heterosigma akashiwo to Allelochemical Linoleic Acid: Growth Inhibition, Oxidative Stress and Apoptosis

2022 ◽  
Vol 8 ◽  
Author(s):  
Renjun Wang ◽  
Qian Liu
Keyword(s):  
Oxidative Stress ◽  
Linoleic Acid ◽  
Algal Blooms ◽  
Morphological Changes ◽  
Flow Cytometric Analysis ◽  
Heterosigma Akashiwo ◽  
Dependent Manner ◽  
Enzymatic Antioxidants ◽  
Apoptotic Pathway ◽  
Allelopathic Effects

Algal blooms have been occurring in many regions worldwide, and allelochemicals are important algaecides used to control harmful algal blooms (HABs). The allelopathic effects of linoleic acid (LA) on the harmful raphidophyte Heterosigma akashiwo were studied, and the possible mechanisms were investigated through analyses of population growth dynamics, cellular ultrastructure and the physiological levels of H. akashiwo. The results showed that the inhibitory effect of LA on H. akashiwo cells increased with an increasing LA concentration. The levels of ROS and MDA were significantly elevated, indicating oxidative stress and lipid peroxidation due to LA exposure. At the same time, LA also activated the antioxidant system, including superoxide dismutase (SOD), catalase (CAT), and POD, and non-enzymatic antioxidants such as reduced AsA and glutathione (GSH). Transmission electron microscopy (TEM) revealed that the morphology of the algal cells was impaired in an LA-dependent manner. Annexin V-FITC/PI double staining and flow cytometric analysis revealed that LA exposure decreased the cellular mitochondrial membrane potential (MMP), increased the rate of apoptosis. LA modulated bcl-2/bax homeostasis and increased the expressions of cytochrome c and caspases-3 and -9, proving that LA induced cell death via the mitochondria-mediated apoptotic pathway. It was suggested that LA had allelopathic effects on H. akashiwo, inducing physiological and morphological changes and finally triggering the apoptosis of H. akashiwo. All of these results showed that LA might have the potential as an algaecide to control harmful algae.

scholarly journals SUMO-Activating Enzyme Subunit 1 (SAE1) Is a Promising Diagnostic Cancer Metabolism Biomarker of Hepatocellular Carcinoma

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 178
Author(s):  
Jiann Ruey Ong ◽  
Oluwaseun Adebayo Bamodu ◽  
Nguyen Viet Khang ◽  
Yen-Kuang Lin ◽  
Chi-Tai Yeh ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Metabolism ◽  
Interaction Analysis ◽  
Normal Liver ◽  
Diagnostic Value ◽  
Vital Role ◽  
Regulation Of Transcription ◽  
Dependent Manner ◽  
Post Translational Modification ◽  
Characteristic Analysis

Hepatocellular carcinoma (HCC) is one of the most diagnosed malignancies and a leading cause of cancer-related mortality globally. This is exacerbated by its highly aggressive phenotype, and limitation in early diagnosis and effective therapies. The SUMO-activating enzyme subunit 1 (SAE1) is a component of a heterodimeric small ubiquitin-related modifier that plays a vital role in SUMOylation, a post-translational modification involving in cellular events such as regulation of transcription, cell cycle and apoptosis. Reported overexpression of SAE1 in glioma in a stage-dependent manner suggests it has a probable role in cancer initiation and progression. In this study, hypothesizing that SAE1 is implicated in HCC metastatic phenotype and poor prognosis, we analyzed the expression of SAE1 in several cancer databases and to unravel the underlying molecular mechanism of SAE1-associated hepatocarcinogenesis. Here, we demonstrated that SAE1 is over-expressed in HCC samples compared to normal liver tissue, and this observed SAE1 overexpression is stage and grade-dependent and associated with poor survival. The receiver operating characteristic analysis of SAE1 in TCGA−LIHC patients (n = 421) showed an AUC of 0.925, indicating an excellent diagnostic value of SAE1 in HCC. Our protein-protein interaction analysis for SAE1 showed that SAE1 interacted with and activated oncogenes such as PLK1, CCNB1, CDK4 and CDK1, while simultaneously inhibiting tumor suppressors including PDK4, KLF9, FOXO1 and ALDH2. Immunohistochemical staining and clinicopathological correlate analysis of SAE1 in our TMU-SHH HCC cohort (n = 54) further validated the overexpression of SAE1 in cancerous liver tissues compared with ‘normal’ paracancerous tissue, and high SAE1 expression was strongly correlated with metastasis and disease progression. The oncogenic effect of upregulated SAE1 is associated with dysregulated cancer metabolic signaling. In conclusion, the present study demonstrates that SAE1 is a targetable cancer metabolic biomarker with high potential diagnostic and prognostic implications for patients with HCC.

scholarly journals Intermedin facilitates hepatocellular carcinoma cell survival and invasion via ERK1/2-EGR1/DDIT3 signaling cascade

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Fei Xiao ◽  
Hongyu Li ◽  
Zhongxue Feng ◽  
Luping Huang ◽  
Lingmiao Kong ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Er Stress ◽  
Cell Survival ◽  
Vascular Remodeling ◽  
Therapeutic Potential ◽  
Blood Perfusion ◽  
Signaling Cascade ◽  
Apoptotic Pathway ◽  
High Level ◽  
Hcc Cells

AbstractAs one of the most malignant cancer types, hepatocellular carcinoma (HCC) is highly invasive and capable of metastasizing to distant organs. Intermedin (IMD), an endogenous peptide belonging to the calcitonin family, has been suggested playing important roles in cancer cell survival and invasion, including in HCC. However, how IMD affects the behavior of HCC cells and the underlying mechanisms have not been fully elucidated. Here, we show that IMD maintains an important homeostatic state by activating the ERK1/2-EGR1 (early growth response 1) signaling cascade, through which HCC cells acquire a highly invasive ability via significantly enhanced filopodia formation. The inhibition of IMD blocks the phosphorylation of ERK1/2, resulting in EGR1 downregulation and endoplasmic reticulum stress (ER) stress, which is evidenced by the upregulation of ER stress marker DDIT3 (DNA damage-inducible transcript 3). The high level of DDIT3 induces HCC cells into an ER-stress related apoptotic pathway. Along with our previous finding that IMD plays critical roles in the vascular remodeling process that improves tumor blood perfusion, IMD may facilitate the acquisition of increased invasive abilities and a survival benefit by HCC cells, and it is easier for HCC cells to obtain blood supply via the vascular remodeling activities of IMD. According to these results, blockade of IMD activity may have therapeutic potential in the treatment of HCC.

scholarly journals 3,3′-Diindolylmethane Suppresses the Growth of Hepatocellular Carcinoma by Regulating Its Invasion, Migration and ER Stress-Mediated Mitochondrial Apoptosis

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1178
Author(s):  
Suvesh Munakarmi ◽  
Juna Shrestha ◽  
Hyun-Beak Shin ◽  
Geum-Hwa Lee ◽  
Yeon-Jun Jeong
Keyword(s):  
Hepatocellular Carcinoma ◽  
Er Stress ◽  
Hepatoma Cell ◽  
Biologically Active ◽  
Migration And Invasion ◽  
Therapeutic Effects ◽  
Dependent Manner ◽  
Mesenchymal Transition ◽  
Huh7 Cells ◽  
Anti Cancer

Hepatocellular carcinoma (HCC) is the leading cause of cancer-related death worldwide with limited treatment options. Biomarker-based active phenolic flavonoids isolated from medicinal plants might shed some light on potential therapeutics for treating HCC. 3,3′-diindolylmethane (DIM) is a unique biologically active dimer of indole-3-carbinol (I3C), a phytochemical compound derived from Brassica species of cruciferous vegetables—such as broccoli, kale, cabbage, and cauliflower. It has anti-cancer effects on various cancers such as breast cancer, prostate cancer, endometrial cancer, and colon cancer. However, the molecular mechanism of DIM involved in reducing cancer risk and/or enhancing therapy remains unknown. The aim of the present study was to evaluate anti-cancer and therapeutic effects of DIM in human hepatoma cell lines Hep3B and HuhCell proliferation was measured with MTT and trypan blue colony formation assays. Migration, invasion, and apoptosis were measured with Transwell assays and flow cytometry analyses. Reactive oxygen species (ROS) intensity and the loss in mitochondrial membrane potential of Hep3B and Huh7 cells were determined using dihydroethidium (DHE) staining and tetramethylrhodamine ethyl ester dye. Results showed that DIM significantly suppressed HCC cell growth, proliferation, migration, and invasion in a concentration-dependent manner. Furthermore, DIM treatment activated caspase-dependent apoptotic pathway and suppressed epithelial–mesenchymal transition (EMT) via ER stress and unfolded protein response (UPR). Taken together, our results suggest that DIM is a potential anticancer drug for HCC therapy by targeting ER-stress/UPR.

scholarly journals Synthesis, Characterization of Nano-β-Tricalcium Phosphate and the Inhibition on Hepatocellular Carcinoma Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Langlang Liu ◽  
Yanzeng Wu ◽  
Chao Xu ◽  
Suchun Yu ◽  
Xiaopei Wu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Particle Size ◽  
Cell Viability ◽  
Tricalcium Phosphate ◽  
Hepg2 Cells ◽  
Drug Carrier ◽  
Average Particle Size ◽  
Crystal Habit ◽  
Average Particle ◽  
Dependent Manner

It is difficult to synthesize nano-β-tricalcium phosphate (nano-β-TCP) owing to special crystal habit. The aim of this work was to synthesize nano-β-TCP using ethanol-water system and characterize it by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Malvern laser particle size analyzer, and transmission electron microscope (TEM). In addition, the inhibitory effect of nano-β-TCP on human hepatocellular carcinoma (HepG2) cells was also investigated using MTT assay, lactate dehydrogenase (LDH) leakage test, and 4′-6-diamidino-2-phenylindole (DAPI) staining. The results showed that negatively charged rod-like nano-β-TCP with about 55 nm in diameter and 120 nm in length was synthesized, and the average particle size of nano-β-TCP was 72.7 nm. The cell viability revealed that nano-β-TCP caused reduced cell viability of HepG2 cells in a time- and dose-dependent manner. These findings presented here may provide valuable reference data to guide the design of nano-β-TCP-based anticancer drug carrier and therapeutic systems in the future.

Docosahexaenoic Acid, a Peroxisome Proliferator-Activated Receptor-α Activator, Induces Apoptosis in Vascular Smooth Muscle Cells by Activation of P38 Mitogen-Activated Protein Kinase

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 679-679
Author(s):  
Quy N Diep ◽  
Rhian M Touyz ◽  
Ernesto L Schiffrin
Keyword(s):  
Smooth Muscle ◽  
Cytochrome C ◽  
Docosahexaenoic Acid ◽  
Vascular Smooth Muscle ◽  
Morphological Changes ◽  
Mitogen Activated Protein Kinase ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Mitogen Activated Protein ◽  
P38 Mapks

9 Omega-3 fatty acids (n-3 FAs) exert a blood pressure-lowering effect in hypertension, possibly by influencing vascular structure. We previously demonstrated that n-3 FAs might induce vascular smooth muscle cell (VSMC) apoptosis, which could exert an effect on structure of blood vessels. This study investigated signaling pathways through which n-3 FAs mediate apoptosis in VSMCs. Cultured Mesenteric VSMCs from Sprague Dawley rats were stimulated with docosahexaenoic acid (DHA), a representative n-3 FA. Morphological changes of apoptosis and DNA fragmentation were examined by phase-contrast microscopy and fluorescence microscopy with Hoechst 33342 staining. To clarify possible pathways of apoptosis, expression of phosphorylated p38 mitogen-activated protein kinases (p38 MAPKs), bax, bcl-2, cytochrome C and peroxisome proliferator-activated receptors-α (PPARs-α) was evaluated by Western blot analysis. DHA treatment induced cell shrinkage, cell membrane blebbing and apoptotic bodies in VSMCs. DHA increased apoptosis (%) in a time-dependent manner to 1.5±0.1, 3.6±0.5, 7.1±0.4, 22.5±0.6, 50.8±1.8 and 61.4±0.9 after 0, 1, 3, 6, 17, and 24 h, respectively. DHA time-dependently activated p38 MAPKs, bax, PPARs-α and cytochrome C with maximal effects obtained after 5, 30 min, 1 h and 3 h, respectively to 551±42, 245±55, 310±12 and 407±14.7 % of controls, respectively. SB-203580 (10 -5 M) and SB-202190 (10 -5 M), selective p38 inhibitors, reduced DHA-elicited apoptosis and expression of PPARs-α, but had no effect on expression of bax or cytochrome C. The present results indicate that DHA induces apoptosis in VSMCs through at least two distinct mechanisms: (i) a p38-dependent pathway that regulates PPAR-α and (ii) a p38-independent pathway via dissipation of mitochondrial transmembrane potential. The death-signaling pathway mediated by DHA may involve an integration of these multiple pathways. By triggering VSMC apoptosis, DHA could play a pathophysiological role in vascular remodeling in cardiovascular disease.

Effect of methyl farnesoate and farnesoic acid during 5th zoea and megalopa metamorphosis in the mud crab Scylla paramamosain Estampador, 1950 (Decapoda, Brachyura, Portunidae)

Crustaceana ◽  
2021 ◽  
Vol 94 (7) ◽  
pp. 855-863
Author(s):  
Ming Zhao ◽  
Fengying Zhang ◽  
Wei Wang ◽  
Zhiqiang Liu ◽  
Lingbo Ma
Keyword(s):  
Larval Development ◽  
Morphological Changes ◽  
Scylla Paramamosain ◽  
Dependent Manner ◽  
Mud Crab ◽  
Methyl Farnesoate ◽  
Concentration Dependent Manner ◽  
Low Levels ◽  
Juvenile Crab ◽  
Farnesoic Acid

Abstract The mud crab Scylla paramamosain is one of the economically important aquaculture species in China. The larval development of the mud crab is characterized by two significant morphological changes, from the 5th zoea (Z5) to the megalopa (M) stage and from the M to the first juvenile crab (C1) stage. In this study, we found that methyl farnesoate (MF) could prohibit the Z5 to M metamorphosis in a concentration-dependent manner, and that a concentration of 10 μM MF could completely prohibit the Z5 metamorphosis. Farnesoic acid (FA) could also prohibit the Z5 metamorphosis, but its effects seemed to be concentration-independent. In addition, MF could delay rather than prohibit the M to C1 metamorphosis, while FA had no effect on the M to C1 metamorphosis at all. To summarize, it is hypothesized that either absence of MF and FA, or at least very low levels of these substances, might be necessary for a successful Z5 to M metamorphosis.

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