Modified Ginseng Extract Induces Apoptosis in HepG2 Cancer Cells by Blocking the CXCL8-Mediated Akt/Nuclear Factor-κB Signaling Pathway

Cui, Zhen; Jo, Eunbi; Jang, Hyun Jin; Hwang, In-Hu; Lee, Kyung‐Bok; Yoo, Hwa‐Seung; Park, Soo Jung; Jung, Mi-Kyung; Lee, Yeon Wol; Jang, Ik‐Soon

doi:10.1142/s0192415x18500842

Cited by 5 publications

(5 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…IL-8 activates nuclear factor (NF)-γ B signaling, but its role in apoptosis induced through the negative regulation of IL-8 remains unclear. 35 could inhibit the GSK-3β-induced processes, including the production of ROS and the decrease in the MTMP. Thus, GSK-3beta could increase the expression of ROS, and IL-8 could inhibit this process, but IL-8 had no direct impact on ROS.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

IL‐8 protects prostate cancer cells from GSK‐3β‐induced oxidative stress by activating the mTOR signaling pathway

Sun

Jin

et al. 2019

The Prostate

View full text Add to dashboard Cite

Introduction Both oxidative stress and inflammation play important roles in prostate cancer cell apoptosis or proliferation; however, the mechanisms underlying these processes remain unclear. Thus, we selected interleukin‐8 (IL‐8) as the bridge between inflammation and cancer cell oxidative stress‐induced death and aimed to confirm its connection with mTOR and Glycogen synthase kinase‐3 beta (GSK‐3β). Methods We overexpressed GSK‐3β and observed its effect on reactive oxygen species (ROS) and oxidative stress‐induced cell death. IL‐8 was then upregulated or downregulated to determine its impact on preventing cell damage due to GSK‐3β‐induced oxidative stress. In addition, we overexpressed or knocked down mTOR to confirm its role in this process. Real‐time PCR, Western blotting, transcription, Cell Counting Kit 8 (CCK‐8), and flow cytometry analyses were performed in addition to the use of other techniques. Results IL‐8 promotes prostate cancer cell proliferation and decreases apoptosis, whereas GSK‐3β activates the caspase‐3 signaling pathway by increasing ROS and thereby induces oxidative stress‐mediated cell death. In addition, mTOR can also decrease activation of the caspase‐3 signaling pathway by inhibiting GSK‐3 and thus decreasing ROS production. Moreover, the inhibitory effect of IL‐8 on GSK‐3β occurs through the regulation of mTOR. Conclusion The results of this study highlight the importance of GSK‐3β, which increases the production of ROS and thereby induces oxidative stress in tumor cells, whereas IL‐8 and mTOR attenuate oxidative stress to protect prostate cancer cells through inhibition of GSK‐3β.

show abstract

Section: Discussionmentioning

confidence: 99%

“…IL‐8 is produced in the tumor microenvironment and plays an important role in cancer pathogenesis. IL‐8 activates nuclear factor (NF)‐γ B signaling, but its role in apoptosis induced through the negative regulation of IL‐8 remains unclear . In addition, very few experiments have focused on the impact of IL‐8 on GSK‐3β.…”

Section: Discussionmentioning

confidence: 99%

IL‐8 protects prostate cancer cells from GSK‐3β‐induced oxidative stress by activating the mTOR signaling pathway

Sun

Jin

et al. 2019

The Prostate

View full text Add to dashboard Cite

show abstract

“…Immunoblotting SKOV-3 cells treated with CME or PBS (vehicle) were lysed in ice-cold lysis buffer (20 mM Tris-HCl, pH 8.0) supplemented with 1% protease Inhibitor cocktail (sigma, P8340) and 1% phosphatase inhibitor cocktail 1,2 and 3 (sigma, P2850, P5726, and P0044) as described previously [38]. The cell homogenate was slowly inverted in 4°C for 45 min before centrifugation (10 min, 12,000 rpm, 4°C).…”

Section: Gene Ontology-based Network Analysismentioning

confidence: 99%

Cordyceps militaris induces apoptosis in ovarian cancer cells through TNF-α/TNFR1-mediated inhibition of NF-κB phosphorylation

Jang

Yang

et al. 2020

BMC Complement Med Ther

Self Cite

149

View full text Add to dashboard Cite

Background: Cordyceps militaris (L.) Fr. (C. militaris) exhibits pharmacological activities, including antitumor properties, through the regulation of the nuclear factor kappa B (NF-κB) signaling. Tumor Necrosis Factor (TNF) and TNF-α modulates cell survival and apoptosis through NF-κB signaling. However, the mechanism underlying its mode of action on the NF-κB pathway is unclear. Methods: Here, we analyzed the effect of C. militaris extract (CME) on the proliferation of ovarian cancer cells by confirming viability, morphological changes, migration assay. Additionally, CME induced apoptosis was determined by apoptosis assay and apoptotic body formation under TEM. The mechanisms of CME were determined through microarray, immunoblotting and immunocytochemistry. Results: CME reduced the viability of cells in a dose-dependent manner and induced morphological changes. We confirmed the decrease in the migration activity of SKOV-3 cells after treatment with CME and the consequent induction of apoptosis. Immunoblotting results showed that the CME-mediated upregulation of tumor necrosis factor receptor 1 (TNFR1) expression induced apoptosis of SKOV-3 cells via the serial activation of caspases. Moreover, CME negatively modulated NF-κB activation via TNFR expression, suggestive of the activation of the extrinsic apoptotic pathway. The binding of TNF-α to TNFR results in the disassociation of IκB from NF-κB and the subsequent translocation of the active NF-κB to the nucleus. CME clearly suppressed NF-κB translocation induced by interleukin (IL-1β) from the cytosol into the nucleus. The decrease in the expression levels of B cell lymphoma (Bcl)-xL and Bcl-2 led to a marked increase in cell apoptosis. Conclusion: These results suggest that C. militaris inhibited ovarian cancer cell proliferation, survival, and migration, possibly through the coordination between TNF-α/TNFR1 signaling and NF-κB activation. Taken together, our findings provide a new insight into a novel treatment strategy for ovarian cancer using C. militaris.

show abstract

“…Previous review has demonstrated that CXCL8 could be secreted by tumor cells and subsequently promote themselves growth and/or inhibit apoptosis (Liu et al, 2016). Some recent researches again proved this mechanism (Guo et al, 2017;Cui et al, 2018;Jia et al, 2018;Kumar et al, 2019).…”

Section: Promoting Tumor Cells Proliferation and Survival By Novel Me...mentioning

confidence: 91%

CXCL8 in Tumor Biology and Its Implications for Clinical Translation

Xiong

Liao

Qiu

et al. 2022

Front. Mol. Biosci.

View full text Add to dashboard Cite

The chemokine CXCL8 has been found to play an important role in tumor progression in recent years. CXCL8 activates multiple intracellular signaling pathways by binding to its receptors (CXCR1/2), and plays dual pro-tumorigenic roles in the tumor microenvironment (TME) including directly promoting tumor survival and affecting components of TME to indirectly facilitate tumor progression, which include facilitating tumor cell proliferation and epithelial-to-mesenchymal transition (EMT), pro-angiogenesis, and inhibit anti-tumor immunity. More recently, clinical trials indicate that CXCL8 can act as an independently predictive biomarker in patients receiving immune checkpoint inhibitions (ICIs) therapy. Preclinical studies also suggest that combined CXCL8 blockade and ICIs therapy can enhance the anti-tumor efficacy, and several clinical trials are being conducted to evaluate this therapy modality.

show abstract

Modified Ginseng Extract Induces Apoptosis in HepG2 Cancer Cells by Blocking the CXCL8-Mediated Akt/Nuclear Factor-κB Signaling Pathway

Cited by 5 publications

References 39 publications

IL‐8 protects prostate cancer cells from GSK‐3β‐induced oxidative stress by activating the mTOR signaling pathway

IL‐8 protects prostate cancer cells from GSK‐3β‐induced oxidative stress by activating the mTOR signaling pathway

Cordyceps militaris induces apoptosis in ovarian cancer cells through TNF-α/TNFR1-mediated inhibition of NF-κB phosphorylation

CXCL8 in Tumor Biology and Its Implications for Clinical Translation

Contact Info

Product

Resources

About