A novel inhibitor, 16-hydroxy-cleroda-3,13-dien-16,15-olide, blocks the autophosphorylation site of focal adhesion kinase (Y397) by molecular docking

Thiyagarajan, Varadharajan; Lin, Shih-Hung; Chia, Yi‐Chen; Weng, Ching‐Feng

doi:10.1016/j.bbagen.2013.04.027

Cited by 45 publications

(32 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This may provide a novel therapeutic option to elucidate the relationship between autophagy, cell death, and response to anticancer agents in glioma and neuroblastoma cells. Combining the present data with those of our previous study (Thiyagarajan et al, 2013), HCD is shown to have multifactorial effects on antitumorigenesis and anti-metastasis, suggesting its potential for development as a promising lead compound for cancer therapy.…”

Section: Discussionsupporting

confidence: 81%

“…Recently, a natural compound, thymoquinone, has been shown to exhibit a caspase-independent manner and autophagic cell death through the activation of JNK and p38 in CPT-11-R LoVo colon cancer cells (Chen et al, 2015). In our previous results, it was revealed that HCD could induce apoptosis through a caspase-independent mechanism (Thiyagarajan et al, 2013). However, the precise role of HCD in autophagy remains unclear.…”

Section: Discussionmentioning

confidence: 96%

“…Our previous results demonstrated that HCD showed an IC50 value at the concentration of 6 M, and cisplatin showed an IC50 value at 10 M in N18 and C6 cell lines, respectively (Thiyagarajan et al, 2013). Hence, these concentrations were used for the subsequent experiments in this study.…”

Section: Lactate Dehydrogenase (Ldh) Productions In Hcd-induced Of N1mentioning

confidence: 97%

“…Several studies also found that modulation of autophagy sensitizes brain tumor cells to standard radiotherapy and chemotherapy-induced death (Kaza et al, 2012). HCD could be a potential inhibitor of FAK and potentially used for anti-tumorigenesis and anti-metastasis treatments in our previous reports (Thiyagarajan et al, 2013(Thiyagarajan et al, , 2016b. However, the effect of HCD in regulating the autophagy of brain tumor cell lines neuroblastoma N18 and glioma C6 is still unclear.…”

Section: Introductionmentioning

confidence: 95%

See 3 more Smart Citations

16-hydroxy-cleroda-3,13-dien-16,15-olide induced glioma cell autophagy via ROS generation and activation of p38 MAPK and ERK-1/2

Thiyagarajan

Sivalingam

Viswanadha

et al. 2016

Environmental Toxicology and Pharmacology

Self Cite

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 96%

Section: Lactate Dehydrogenase (Ldh) Productions In Hcd-induced Of N1mentioning

confidence: 97%

Section: Introductionmentioning

confidence: 95%

See 2 more Smart Citations

16-hydroxy-cleroda-3,13-dien-16,15-olide induced glioma cell autophagy via ROS generation and activation of p38 MAPK and ERK-1/2

Thiyagarajan

Sivalingam

Viswanadha

et al. 2016

Environmental Toxicology and Pharmacology

Self Cite

View full text Add to dashboard Cite

“…MMP-2 and MMP-9 abundantly expressed in various cancers, are considered to play key roles in tumor invasion and metastasis [19]. In addition, mounting evidence suggests that inhibition of MMP-9 and MMP-2 by chemopreventive agents suppresses the invasiveness and metastases of many cancer cells [20,21].…”

Section: Discussionmentioning

confidence: 99%

Thymol inhibits cell migration and invasion by downregulating the activation of PI3K/AKT and ERK pathways in human colon cancer cells

Lv¹,

Chen²

2018

Trop. J. Pharm Res

View full text Add to dashboard Cite

Purpose: To assess the anti-metastasis effects of thymol on human colorectal cancer cells. Methods: Human colorectal adenocarcinoma cell HT29 was incubated with varying concentrations of thymol. Cell viability, migration and invasion were determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-dipheny-tetrazoliumbromide (MTT) and Transwell assays, respectively. Matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9) were analyzed by gel zymogram assay. Epithelial-mesenchymal transition (EMT)-associated gene expression and signaling pathway were analyzed using real-time quantitative polymerase chain reaction (PCR) and Western blotting, respectively. Results: Thymol was significantly inhibited migration and invasion of HT29 cell (p < 0.01) and also markedly reduced the activity of matrix degrading enzymes MMP-2 and MMP-9 (p < 0.01). Moreover, the epithelial marker, E-cadherin, was elevated, while mesenchymal markers (vimentin and α-SMA), and associated transcription factors (snail and slug) decreased after thymol treatment (p < 0.01). In addition, thymol inhibited the phosphorylation of PI3K/AKT and ERK pathways (p < 0.01). Conclusion: Thymol efficiently attenuates cell migration and invasion by decreasing EMT and downregulating the activation of PI3K/AKT and ERK signaling pathways in colorectal adenocarcinoma cells. It is, thus, a potential candidate drug for the management of colorectal cancer.Keywords : Thymol, Colorectal cancer, Vimentin, PI3K/AKT and ERK pathway

show abstract

Anticancer activities of chalcone flavokawain B from Alpinia pricei Hayata in human lung adenocarcinoma (A549) cells via induction of reactive oxygen species‐mediated apoptotic and autophagic cell death

Hseu

Hui

Thiyagarajan

et al. 2019

Journal Cellular Physiology

Self Cite

View full text Add to dashboard Cite

Chalcones found in fruits and vegetables have promising cancer chemopreventive properties. This study attempts to identify the anticancer efficacies of chalcone flavokawain B (FKB) in the rhizomes of Alpinia pricei Hayata by examining key molecular events in non‐small‐cell lung cancer (A549) cells. Our results indicated that in human A549 cells, FKB (0–15 μg/ml) decreases cell viability and colony formation, dysregulates the Bax:B‐cell lymphoma 2 ratio and increases apoptotic DNA fragmentation. Mitochondrial (caspase‐9/‐3 and poly ADP ribose polymerase [PARP]) signaling was found to be involved in FKB‐induced apoptosis. In addition, FKB‐induced reactive oxygen species (ROS) generation, and N‐acetylcysteine attenuated FKB‐induced apoptotic cell death. Moreover, FKB triggered autophagy, as evidenced by the improved acidic vesicular organelle formation, lipidated light chain 3 (microtubule‐related light chain 3) accumulation, and ATG7 expression and the decreased mammalian target of rapamycin phosphorylation. Furthermore, FKB suppressed ROS‐mediated ATG4B expression. Inhibiting autophagy using 3‐methyladenine/chloroquine diminished FKB‐induced cell death, indicating that autophagy is triggered as a death mechanism by FKB. In summary, FKB has a crucial role in the execution and propagation of ROS‐mediated apoptotic and autophagic cell death of lung adenocarcinoma cells.

show abstract

A novel inhibitor, 16-hydroxy-cleroda-3,13-dien-16,15-olide, blocks the autophosphorylation site of focal adhesion kinase (Y397) by molecular docking

Cited by 45 publications

References 41 publications

16-hydroxy-cleroda-3,13-dien-16,15-olide induced glioma cell autophagy via ROS generation and activation of p38 MAPK and ERK-1/2

16-hydroxy-cleroda-3,13-dien-16,15-olide induced glioma cell autophagy via ROS generation and activation of p38 MAPK and ERK-1/2

Thymol inhibits cell migration and invasion by downregulating the activation of PI3K/AKT and ERK pathways in human colon cancer cells

Anticancer activities of chalcone flavokawain B from Alpinia pricei Hayata in human lung adenocarcinoma (A549) cells via induction of reactive oxygen species‐mediated apoptotic and autophagic cell death

Contact Info

Product

Resources

About