scholarly journals Achillin Increases Chemosensitivity to Paclitaxel, Overcoming Resistance and Enhancing Apoptosis in Human Hepatocellular Carcinoma Cell Line Resistant to Paclitaxel (Hep3B/PTX)

Pharmaceutics ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 512 ◽  
Author(s):  
Sanchez-Carranza ◽  
González-Maya ◽  
Razo-Hernández ◽  
Salas-Vidal ◽  
Nolasco-Quintana ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Sesquiterpene Lactones ◽  
Phase Cell ◽  
Glycoprotein P ◽  
Cycle Arrest ◽  
P Glycoprotein ◽  
M Phase ◽  
Docking Calculations ◽  
Hepatocellular Carcinoma Cell Line ◽  
Human Hepatocellular Carcinoma Cell

Multidrug resistance (MDR) has become a major obstacle in the treatment of cancer, and is associated with mechanisms such as increased drug outflow, reduction of apoptosis, and/or altered drug metabolism. These problems can be mitigated by the coadministration of agents known as chemosensitizers, as they can reverse resistance to anticancer drugs and eventually resensitize cancer cells. We explore the chemosensitizing effect of Achillin, a guaianolide-type sesquiterpene lactone isolated from the Mexican medicinal plant Artemisia ludovisiana, to reverse MDR in Hep3B/PTX cells of hepatocellular carcinoma, which present resistance to paclitaxel (PTX). Achillin showed an important effect as chemosensitizer; indeed, the cytotoxic effect of PTX (25 nM) was enhanced, and the induction of G2/M phase cell cycle arrest and apoptosis were potentiated when combining with Achillin (100 μM). In addition, we observed that Achillin decreases P-gp levels and increases the intracellular retention of doxorubicin in Hep3B/PTX cells; in addition, homology structural modeling and molecular docking calculations predicted that Achillin interacts in two regions (M-site and R-site) of transporter drug efflux P-glycoprotein (P-gp). Our results suggest that the chemosensitizer effect demonstrated for Achillin could be associated with P-gp modulation. This work also provides useful information for the development of new therapeutic agents from guaianolide-type sesquiterpene lactones like Achillin.

Involvement of the role of Chk1 in lithium‐induced G2/M phase cell cycle arrest in hepatocellular carcinoma cells

2008 ◽  
Vol 104 (4) ◽  
pp. 1181-1191 ◽  
Author(s):  
Xiao‐Ming Wang ◽  
Jiao Li ◽  
Xiao‐Cheng Feng ◽  
Qiong Wang ◽  
Dong‐Yin Guan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Carcinoma Cells ◽  
Phase Cell ◽  
Hepatocellular Carcinoma Cells ◽  
Cycle Arrest ◽  
M Phase

scholarly journals α-pinene regulates miR-221 and induces G2/M phase cell cycle arrest in human hepatocellular carcinoma cells

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Qiuxiang Xu ◽  
Ming Li ◽  
Mengdie Yang ◽  
Jiebo Yang ◽  
Jingjing Xie ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Hepg2 Cells ◽  
Carcinoma Cells ◽  
Phase Cell ◽  
Hepatocellular Carcinoma Cells ◽  
Cycle Arrest ◽  
M Phase ◽  
Dependent Growth

The naturally occurring compound α-pinene induces cell cycle arrest and antitumor activity. We examined effects of α-pinene on cell cycle regulation in hepatocellular carcinoma cells (HepG2) cells to establish a foundation for its development as a novel treatment for hepatocellular carcinoma (HCC). HepG2 cells treated with α-pinene exhibited dose-dependent growth inhibition as a result of G2/M-phase cell cycle arrest. Cell cycle arrest was associated with down-regulated cyclin-dependent kinase 1 (CDK1) and miR-221 levels and up-regulated levels of CDKN1B/p27, γ-H2AX, phosphorylated ATM, phosphorylated Chk2 and phosphorylated p53. Our observations are consistent with a model in which α-pinene inhibits miR221 expression, which leads to G2/M-phase arrest and activation of CDKN1B/p27-CDK1 and ATM-p53-Chk2 pathways that suppress human hepatoma tumor progression. Additionally, α-pinene was found to trigger oxidative stress and induce apoptosis of HepG2 cells. α-pinene, therefore, represents a potential chemotherapeutic compound for the treatment of HCC.

scholarly journals Insight into Bortezomib Focusing on Its Efficacy against P-gp-Positive MDR Leukemia Cells

2021 ◽  
Vol 22 (11) ◽  
pp. 5504
Author(s):  
Tomáš Kyca ◽  
Lucia Pavlíková ◽  
Viera Boháčová ◽  
Anton Mišák ◽  
Alexandra Poturnayová ◽  
...  
Keyword(s):  
T Cells ◽  
26S Proteasome ◽  
Gene Encoding ◽  
Glycoprotein P ◽  
Cyclin Dependent Kinases ◽  
Cycle Arrest ◽  
P Glycoprotein ◽  
M Phase ◽  
Genes Encoding ◽  
Insight Into

In this paper, we compared the effects of bortezomib on L1210 (S) cells with its effects on P-glycoprotein (P-gp)-positive variant S cells, which expressed P-gp either after selection with vincristine (R cells) or after transfection with a human gene encoding P-gp (T cells). Bortezomib induced the death-related effects in the S, R, and T cells at concentrations not exceeding 10 nM. Bortezomib-induced cell cycle arrest in the G2/M phase was more pronounced in the S cells than in the R or T cells and was related to the expression levels of cyclins, cyclin-dependent kinases, and their inhibitors. We also observed an increase in the level of polyubiquitinated proteins (via K48-linkage) and a decrease in the gene expression of some deubiquitinases after treatment with bortezomib. Resistant cells expressed higher levels of genes encoding 26S proteasome components and the chaperone HSP90, which is involved in 26S proteasome assembly. After 4 h of preincubation, bortezomib induced a more pronounced depression of proteasome activity in S cells than in R or T cells. However, none of these changes alone or in combination sufficiently suppressed the sensitivity of R or T cells to bortezomib, which remained at a level similar to that of S cells.

Effects of thonningianin A in natural foods on apoptosis and cell cycle arrest of HepG-2 human hepatocellular carcinoma cells

2015 ◽  
Vol 6 (8) ◽  
pp. 2588-2597 ◽  
Author(s):  
Tian-Tian Zhang ◽  
Li Yang ◽  
Jian-Guo Jiang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Carcinoma Cell ◽  
Carcinoma Cells ◽  
Human Hepatocellular Carcinoma ◽  
Cycle Arrest ◽  
Anti Cancer ◽  
Hepatocellular Carcinoma Cell Line ◽  
Human Hepatocellular Carcinoma Cell ◽  
Natural Foods ◽  
Human Hepatocellular Carcinoma Cells

The anti-cancer activities of Thonningianin A on the HepG-2 human hepatocellular carcinoma cell line were evaluated by MTT assay, flow cytometry, quantitative real-time PCR and western blotting.

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