Shikonin Induces Apoptotic Cell Death via Regulation of p53 and Nrf2 in AGS Human Stomach Carcinoma Cells

Ko, Hyeonseok; Kim, Sun Joong; Shim, So Hee; Chang, Hyolhl; Ha, Chang Hoon

doi:10.4062/biomolther.2016.008

Cited by 32 publications

(18 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The up-regulation of p73 and down-regulation of ICBP90 during the shikonin treatment also led to the apoptosis of human cancer cells [20]. Shikonin could induce apoptosis, necrosis by up-regulating p53 and Nrf2 expression in lung cancer and stomach carcinoma [21, 22]. Therefore, to study the effect of shikonin on the CCA cells is significant for the new method of clinical therapy in CCA.…”

Section: Introductionmentioning

confidence: 99%

TRAIL Enhances Shikonin Induced Apoptosis through ROS/JNK Signaling in Cholangiocarcinoma Cells

Zhou

Yang

Wang

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Cholangiocarcinoma (CCA), arising from varying locations within the biliary tree, is the second most common primary liver malignancy worldwide. Shikonin, an active compound extracted from the Chinese herb Zicao, holds anti-bacterial, anti-inflammatory, and anti-tumor activities. However, the effect of shikonin on human cholangiocarcinoma and detailed mechanisms of TRAIL enhancement remains to be elucidated. The purpose of the study was to investigate the protective functions of TRAIL enhancement for shikonin induced apoptosis in cholangiocarcinoma cells. Methods: We use MTT assay, apoptosis assay, caspase activity assay, flow cytometry assay, real time PCR and Western blot to observe the effects of TRAIL on shikonin induced cholangiocarcinoma cells apoptosis and its mechanism. Results: Shikonin inhibited cell viability and induced apoptosis of CCA cells, effects enhanced by TRAIL treatment via activation of caspase-3, -8, -9. Furhermore, TRAIL enhanced anti-proliferation of shikonin and shikonin induced apoptosis through induction of ROS mediated JNK activation, while AKT activation had an effect on shikonin anti-proliferation activity, but not in the TRAIL enhanced counterparts. Finally, shikonin upregulated DR5 expression, an effect essential for TRAIL-enhanced activities of shikonin in RBE cells. Conclusions: Our results revealed that shikonin could inhibit cells viability and induce apoptosis of CCA cells, effects enhanced by TRAIL treatment via ROS mediated JNK signalling pathways, involving up-regulation of DR5 expression. Our results provide further insight into the mechanism underlying the anti-tumor effects of shikonin by TRAIL enhanced in CCA and a new therapeutic strategy to CCA treatment.

show abstract

Section: Introductionmentioning

confidence: 99%

TRAIL Enhances Shikonin Induced Apoptosis through ROS/JNK Signaling in Cholangiocarcinoma Cells

Zhou

Yang

Wang

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…Natural anticancer compounds inhibit tumor growth and progression by reducing cell migration, invasion, and metastasis [ 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ]. Interestingly, chalcone-like chain CTI-82 exhibits several pharmacological effects.…”

Section: Discussionmentioning

confidence: 99%

A New TGF-β1 Inhibitor, CTI-82, Antagonizes Epithelial–Mesenchymal Transition through Inhibition of Phospho-SMAD2/3 and Phospho-ERK

Jeong

Kim

Park

et al. 2020

Biology

View full text Add to dashboard Cite

Transforming growth factor-β1 (TGF-β1) is highly expressed in the tumor microenvironment and known to play a multifunctional role in cancer progression. In addition, TGF-β1 promotes metastasis by inducing epithelial–mesenchymal transition (EMT) in a variety of tumors. Thus, inhibition of TGF-β1 is considered an important strategy in the treatment of cancer. In most tumors, TGF-β1 signal transduction exhibits modified or non-functional characteristics, and TGF-β1 inhibitors have various inhibitory effects on cancer cells. Currently, many studies are being conducted to develop TGF-β1 inhibitors from non-toxic natural compounds. We aimed to develop a new TGF-β1 inhibitor to suppress EMT in cancer cells. As a result, improved chalcone-like chain CTI-82 was identified, and its effect was confirmed in vitro. We showed that CTI-82 blocked TGF-β1-induced EMT by inhibiting the cell migration and metastasis of A549 lung cancer cells. In addition, CTI-82 reduced the TGF-β1-induced phosphorylation of SMAD2/3 and inhibited the expression of various EMT markers. Our results suggest that CTI-82 inhibits tumor growth, migration, and metastasis.

show abstract

“…Many studies 21 - 23 have found shikonin had antitumor effect in various cancer types, the mechanisms of which were given on the aspects of induction of apoptosis, necrosis, acting on proteasome, protein tyrosine kinase and anti-angiogenesis. The molecular mechanisms mainly included stimulating ROS generation 22 in the mitochondria, inhibiting the activities of DNA topoisomerases, increasing expression of p53 23 , 24 and inhibition of cancer cell glycolysis via targeting PKM2, polo-like kinase1 (PLK1) and protein tyrosine kinase (PTK) 19 , 25 . Compared with previous studies, our study found that shikonin inhibited HIF1α/pkm2/CyclinD1 signal pathway to regulate the proliferation of esophageal cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Shikonin against Esophageal Cancer Cells and its possible mechanisms in vitro and in vivo

Tang¹,

Zhao²,

Long³

et al. 2018

J. Cancer

View full text Add to dashboard Cite

Increasing evidences indicate that shikonin can suppress the tumor growth. However, the mechanisms remain elusive. In the present study, we investigated the effects and mechanisms of shikonin against esophageal cancer. The expression of hypoxia inducible factor 1α (HIF1α) and pyruvate kinase M2 (PKM2) in esophageal cancer tissues and cells was detected by immunohistochemistry and Western blot. CCK-8 was used to examine the esophageal cancer cell viability. Apoptosis and cell cycle were analyzed by flow cytometry. The expression of EGFR, PI3K, Akt, p-AKT, mTOR, HIF1α and PKM2 was detected by Western blot. EC109/pkm2 was established by lentivirus transducer. Ec109 tumor model was founded to observe the antitumor effect of shikonin in vivo.We found that HIF1α and PKM2 protein expression levels were higher in esophageal cancer tissues and cells than normal esophageal tissues and cells. Shikonin reduced esophageal cancer cells viability and induced cell cycle arrest and apoptosis. Shikonin decreased EGFR, PI3K, p-AKT, HIF1α and PKM2 expression. Overexpression of PKM2 could enhance resistance of esophageal cancer cells to shikonin. In vivo we found that shikonin reduced tumor burden, inducing cell arrest and apoptosis. Taken together, shikonin has a significant antitumor effect in the esophageal cancer by regulating HIF1α/PKM2 signal pathway.

show abstract

Shikonin Induces Apoptotic Cell Death via Regulation of p53 and Nrf2 in AGS Human Stomach Carcinoma Cells

Cited by 32 publications

References 30 publications

TRAIL Enhances Shikonin Induced Apoptosis through ROS/JNK Signaling in Cholangiocarcinoma Cells

TRAIL Enhances Shikonin Induced Apoptosis through ROS/JNK Signaling in Cholangiocarcinoma Cells

A New TGF-β1 Inhibitor, CTI-82, Antagonizes Epithelial–Mesenchymal Transition through Inhibition of Phospho-SMAD2/3 and Phospho-ERK

Efficacy of Shikonin against Esophageal Cancer Cells and its possible mechanisms in vitro and in vivo

Contact Info

Product

Resources

About