scholarly journals Incaspitolide A extracted from Carpesium cernuum induces apoptosis in vitro via the PI3K/AKT pathway in benign prostatic hyperplasia

2021 ◽  
Author(s):  
Xiaoyue Chen ◽  
Jingrui Song ◽  
Dongbo Yuan ◽  
Qing Rao ◽  
Kehua Jiang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Benign Prostatic Hyperplasia ◽  
Cell Cycle Arrest ◽  
Cyclin B1 ◽  
Prostatic Hyperplasia ◽  
Phase Cell ◽  
Prolonged Treatment ◽  
Akt Pathway ◽  
Cycle Arrest

Benign prostatic hyperplasia (BPH) is a common disease that occurs mainly in older men. The pathogenesis of BPH is complex and patients face a prolonged treatment course, and novel drugs with better selectivity and lower toxicity are required. incaspitolide A (compound TMJ-12) is a germacrane-type sesquiterpenoid compound extracted from the plant Carpesium carnuum. Extracts of C. carnuum are known to exert suppressive effects on BPH-1 cells. In this study, we investigated the molecular mechanisms underlying the suppressive effect of TMJ-12 specifically on BPH-1 cells. A cytotoxicity assay indicated that TMJ-12 inhibited BPH-1 cell proliferation, while flow cytometry assays showed that TMJ-12 induced G2/M phase cell cycle arrest and the apoptosis of BPH-1 cells. TMJ-12 was also shown to regulate the expression of several apoptosis- and cell cycle-related proteins, namely Bcl-2, Bax, Bad, Caspase-9, Caspase-3, CDK1, Cyclin B1, CDC25C, and c-Myc, among others. Collapse of the mitochondrial membrane potential (ΔΨm) following exposure to TMJ-12 was detected with the JC-1 staining assay. Further investigation revealed that treatment with TMJ-12 inhibited the PI3K/AKT pathway by increasing the expression of PTEN. Taken together, the results suggest that TMJ-12 prevents BPH-1 cell proliferation via the PI3K/AKT pathway by inducing apoptosis and cell cycle arrest.

Antimalarial agent artesunate induces G0/G1 cell cycle arrest and apoptosis via increasing intracellular ROS levels in normal liver cells

2020 ◽  
Vol 39 (12) ◽  
pp. 1681-1689
Author(s):  
S Yin ◽  
H Yang ◽  
X Zhao ◽  
S Wei ◽  
Y Tao ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Arrest ◽  
Normal Liver ◽  
Liver Cells ◽  
Phase Cell ◽  
Normal Cells ◽  
Cycle Arrest ◽  
Intracellular Ros ◽  
G1 Cell Cycle Arrest

Artesunate (ARS) has been shown to be highly effective against chloroquine-resistant malaria. In vitro studies reported that ARS has anticancer effects; however, its detrimental action on cancer cells may also play a role in its toxicity toward normal cells and its potential toxicity has not been sufficiently researched. In this study, we investigated the possible cytotoxic effects using normal BRL-3A and AML12 liver cells. The results showed that ARS dose-dependently inhibited cell proliferation and arrested the G0/G1 phase cell cycle in both BRL-3A and AML12 liver cells. Western blotting demonstrated that ARS induced a significant downregulation of cyclin-dependent kinase-2 (CDK2), CDK4, cyclin D1, and cyclin E1 in various levels and then caused apoptosis when the Bcl-2/Bax ratio decreased. Conversely, the levels of intracellular reactive oxygen species (ROS) were increased. The ROS scavenger N-acetylcysteine can significantly inhibit cell cycle arrest and apoptosis induced by ARS. Thus, the data confirmed that ARS exposure impairs normal liver cell proliferation by inducing G0/G1 cell cycle arrest and apoptosis, and this detrimental action may be associated with intracellular ROS accumulation. Collectively, the possible side effects of ARS on healthy normal cells cannot be neglected when developing therapies.

scholarly journals Dietary Isothiocyanates Inhibit Caco-2 Cell Proliferation and Induce G2/M Phase Cell Cycle Arrest, DNA Damage, and G2/M Checkpoint Activation

2004 ◽  
Vol 134 (11) ◽  
pp. 3121-3126 ◽  
Author(s):  
James M. Visanji ◽  
Susan J. Duthie ◽  
Lynn Pirie ◽  
David G. Thompson ◽  
Philip J. Padfield
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Dna Damage ◽  
Cell Cycle Arrest ◽  
Phase Cell ◽  
Checkpoint Activation ◽  
Cycle Arrest ◽  
M Phase

scholarly journals Ghrelin enhances cisplatin sensitivity in HO-8910 PM human ovarian cancer cells

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yun Leng ◽  
Can Zhao ◽  
Guoliang Yan ◽  
Shuangyue Xu ◽  
Yinggui Yang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cell Cycle Arrest ◽  
Cyclin B1 ◽  
Inhibitory Effect ◽  
S Phase ◽  
Phase Cell ◽  
Ovarian Cancer Cells ◽  
Cycle Arrest

Abstract Background Resistance to platinum-based chemotherapy is one of the crucial problems in ovarian cancer treatment. Ghrelin, a widely distributed peptide hormone, participates in a series of cancer progression. The aim of this study is to determine whether ghrelin influences the sensitivity of ovarian cancer to cisplatin, and to demonstrate the underlying mechanism. Methods The anti-tumor effects of ghrelin and cisplatin were evaluated with human ovarian cancer cells HO-8910 PM in vitro or in vivo. Cell apoptosis and cell cycle were analyzed via flow cytometry assay. The signaling pathway and the expression of cell cycle protein were analyzed with Western Blot. Results Our results showed that treatment with ghrelin specifically inhibited cell proliferation of HO-8910 PM and sensitized these cells to cisplatin via S phase cell cycle arrest, and enhanced the inhibitory effect of cisplatin on tumor growth of HO-8910 PM derived xenografts in vivo. Treatment with ghrelin inhibited the expression of p-Erk1/2 and p-p38, which was opposite the effect of cisplatin. However, under the treatment of ghrelin, cisplatin treatment exhibited a stronger effect on inhibiting P21 expression, upregulating p-CDK1 and cyclin B1 expression, and blocking cell cycle progression. Mechanistically, ghrelin promoted S phase cell cycle arrest and upregulated p-CDK1 and cyclin B1 expression induced by cisplatin via inhibition of p38. Conclusion This study revealed a specifically inhibitory effect of ghrelin on platinum-resistance via suppressing p-P38 and subsequently promoting p-CDK1 mediated cell cycle arrest in HO-8910 PM.

scholarly journals Curcumin Reverses NNMT-Induced 5-Fluorouracil Resistance via Increasing ROS and Cell Cycle Arrest in Colorectal Cancer Cells

Biomolecules ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1295
Author(s):  
Guoli Li ◽  
Sining Fang ◽  
Xiao Shao ◽  
Yejia Li ◽  
Qingchao Tong ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Induced Resistance ◽  
Phase Cell ◽  
Ros Generation ◽  
Antitumor Effects ◽  
Cycle Arrest

Nicotinamide N-methyltransferase (NNMT) plays multiple roles in improving the aggressiveness of colorectal cancer (CRC) and enhancing resistance to 5-Fluorouracil (5-FU), making it an attractive therapeutic target. Curcumin (Cur) is a promising natural compound, exhibiting multiple antitumor effects and potentiating the effect of 5-FU. The aim of the present study is to explore the effect of Cur on attenuating NNMT-induced resistance to 5-FU in CRC. A panel of CRC cell lines with different NNMT expressions are used to characterize the effect of Cur. Herein, it is observed that Cur can depress the expression of NNMT and p-STAT3 in CRC cells. Furthermore, Cur can induce inhibition of cell proliferation, G2/M phase cell cycle arrest, and reactive oxygen species (ROS) generation, especially in high-NNMT-expression CRC cell lines. Cur can also re-sensitize high-NNMT-expression CRC cells to 5-FU both in vitro and in vivo. In summary, it is proposed that Cur can reverse NNMT-induced cell proliferation and 5-FU resistance through ROS generation and cell cycle arrest. Given that Cur has long been used, we suppose that Cur is a promising anticancer drug candidate with minimal side effects for human CRC therapy and can attenuate NNMT-induced resistance to 5-FU.

scholarly journals Banana Flower Extract Suppresses Benign Prostatic Hyperplasia by Regulating the Inflammatory Response and Inducing G1 Cell-cycle Arrest

In Vivo ◽  
2018 ◽  
Vol 32 (6) ◽  
pp. 1373-1379 ◽  
Author(s):  
LIANG-CHIH LIU ◽  
YUNG-HSIANG LIN ◽  
YING-CHAO LIN ◽  
CHI-TANG HO ◽  
CHAO-MING HUNG ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Benign Prostatic Hyperplasia ◽  
Inflammatory Response ◽  
Cell Cycle Arrest ◽  
Prostatic Hyperplasia ◽  
Flower Extract ◽  
Cycle Arrest ◽  
G1 Cell Cycle Arrest ◽  
Banana Flower

Elevated toll-like receptor 3 inhibits pancreatic β-cell proliferation through G1 phase cell cycle arrest

2013 ◽  
Vol 377 (1-2) ◽  
pp. 112-122 ◽  
Author(s):  
Yi Wang ◽  
HuiWen Wu ◽  
LiLi Gao ◽  
ShanShan Chen ◽  
LiZe Gu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Arrest ◽  
Phase Cell ◽  
G1 Phase ◽  
Pancreatic Β Cell ◽  
Toll Like Receptor ◽  
Β Cell ◽  
Cycle Arrest

scholarly journals Scutellarein Induces Fas-Mediated Extrinsic Apoptosis and G2/M Cell Cycle Arrest in Hep3B Hepatocellular Carcinoma Cells

Nutrients ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 263 ◽  
Author(s):  
Ha Sang Eun ◽  
Kim Seong Min ◽  
Lee Ho Jeong ◽  
Preethi Vetrivel ◽  
Venu Venkatarame Gowda Saralamma ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Fas Ligand ◽  
Biological Activities ◽  
Cyclin B1 ◽  
Phase Cell ◽  
Cycle Arrest ◽  
Wide Range ◽  
Hep3b Cells

Scutellarein (SCU), a flavone found in the perennial herb Scutellaria baicalensis, is known for a wide range of biological activities. In the present study, we investigated the effects of treatment with SCU flavonoids on inducing apoptosis via the extrinsic pathway in Hep3B cells. SCU treatment significantly inhibited Hep3B cell proliferation and induced G2/M phase cell cycle arrest by inhibiting the expression levels of the proteins Cdc25C, cdk1 and Cyclin B1. Allophycocyanin (APC)/Annexin V and propidium iodide (PI) double-staining showed upregulation of apoptotic cell death fraction. We further confirmed apoptosis by 4′-6-diamidino-2-phenylindole (DAPI) fluorescent staining and observed DNA fragmentation with agarose gel electrophoresis. Further, immunoblotting results showed that treatment with SCU showed no changes in Bax and Bcl-xL protein levels. In addition, SCU treatment did not affect the mitochondrial membrane potential in Hep3B cells. On the contrary, treatment with SCU increased the expression of Fas and Fas ligand (FasL), which activated cleaved caspase-8, caspase-3, and polymeric adenosine diphosphate ribose (PARP), whereas the expression level of death receptor 4 (DR4) decreased. We confirmed that the proteins expressed upon treatment with SCU were involved in the Fas-mediated pathway of apoptosis in Hep3B cells. Thus, our findings in the current study strongly imply that SCU can be a basic natural source for developing potent anti-cancer agents for hepatocellular carcinoma (HCC) treatment.

scholarly journals Nimbolide Represses the Proliferation, Migration, and Invasion of Bladder Carcinoma Cells via Chk2-Mediated G2/M Phase Cell Cycle Arrest, Altered Signaling Pathways, and Reduced Transcription Factors-Associated MMP-9 Expression

2019 ◽  
Vol 2019 ◽  
pp. 1-12
Author(s):  
Seung-Shick Shin ◽  
Byungdoo Hwang ◽  
Kashif Muhammad ◽  
Yujeong Gho ◽  
Jun-Hui Song ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Bladder Cancer ◽  
Transcription Factors ◽  
Cell Cycle Arrest ◽  
Cyclin B1 ◽  
Chemical Constituent ◽  
Phase Cell ◽  
Migration And Invasion ◽  
Cycle Arrest ◽  
M Phase

Nimbolide, an active chemical constituent of Azadirachta indica, reportedly has several physiological effects. Here, we assessed novel anticancer effects of nimbolide against bladder cancer EJ and 5637 cells. Nimbolide treatment inhibited the proliferation of both bladder cancer cell lines with an IC50 value of 3 μM. Treatment of cells with nimbolide induced G2/M phase cell cycle arrest via both Chk2-Cdc25C-Cdc2/cyclin B1-Wee1 pathway and Chk2-p21WAF1-Cdc2/cyclin B1-Wee1 pathway. Nimbolide increased JNK phosphorylation and decreased p38MAPK and AKT phosphorylation. Additionally, nimbolide impeded both wound healing migration and invasion abilities by suppressing matrix metalloproteinase-9 (MMP-9) activity. Finally, nimbolide repressed the binding activity of NF-κB, Sp-1, and AP-1 motifs, which are key transcription factors for MMP-9 activity regulation. Overall, our study indicates that nimbolide is a potential chemotherapeutic agent for bladder cancer.

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