SP600125 enhances C-2-induced cell death by the switch from autophagy to apoptosis in bladder cancer cells

Yu, Haiyang; Wu, Chunli; Wang, Xiangyu; Ban, QianHong; Quan, Chunhua; Liu, Mengbo; Dong, Hangqi; Li, Jinfeng; Kim, Gi‐Young; Choi, Yung Hyun; Wang, Zhenya; Jin, Cheng‐Yun

doi:10.1186/s13046-019-1467-6

Cited by 31 publications

(29 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, scientific evidences described the JNK role in autophagy through Bcl-2 and Bcl-xL phosphorylation to active Beclin-1 [25]. In particular, as previously described, Bcl-2 and Beclin-1 reduction may be a direct consequence of JNK decrease [26]. Therefore, the results discussed so far support the idea that BCP may also regulate apoptosis and autophagy mechanisms not only through a direct modulation of CB2 receptors but also by JNK modulation.…”

Section: Discussionsupporting

confidence: 76%

β-Caryophyllene Inhibits Cell Proliferation through a Direct Modulation of CB2 Receptors in Glioblastoma Cells

Irrera

D’Ascola

Pallio

et al. 2020

Cancers

View full text Add to dashboard Cite

Glioblastomas are aggressive cancers characterized by uncontrolled proliferation and inflammation. b-caryophyllene (BCP) is a cannabinoid receptor 2 (CB2) agonist that showed an important anti-inflammatory effect through the interaction of CB2 and peroxisome proliferator-activated receptor gamma (PPARg) receptors. BCP effects were investigated in an in vitro model of glioblastoma. U-373 and U87, derived from a human glioblastoma, and human glioma stem-like cells (GSCs) were treated with BCP at different doses and time-points. AM360, a specific CB2 antagonist, was added 2 h before BCP treatment. BCP showed a significant anti-proliferative effect, reducing cell viability, inhibiting cell cycle, and increasing apoptosis, as demonstrated by Tunel assay, caspase-3 and caspase -9 activation. In addition, the pro-apoptotic BAX expression was increased, whereas the anti-apoptotic Bcl-2 expression was reduced. Treatment with BCP decreased Beclin-1, LC3 and p62/SQSTM1 expression, indicating a possible switch of autophagy to apoptosis. BCP’s anti-inflammatory effect was demonstrated by NF-κB reduction, PPARg activation and TNF-a decrease; BCP significantly reduced Jun N-Terminal Kinase (JNK) expression as a consequence of TNF-α inhibition. AM360 abrogated BCP effects, thus demonstrating the BCP mechanism of action through the CB2 receptor. These findings let us hypothesize that BCP may act as a tumor suppressor in glioblastoma, acting on CB2 receptor and modulating JNK.

show abstract

Section: Discussionsupporting

confidence: 76%

β-Caryophyllene Inhibits Cell Proliferation through a Direct Modulation of CB2 Receptors in Glioblastoma Cells

Irrera

D’Ascola

Pallio

et al. 2020

Cancers

View full text Add to dashboard Cite

show abstract

“…Multiple agents in development in preclinical and clinical trials and even many clinical drugs have been found to trigger cytoprotective autophagy, including mTOR inhibitors, kinase inhibitors, natural products, and antiangiogenic agents (Haiyang Yu et al, 2019;Mei-Chuan Chen et al, 2019). Meanwhile, various signaling pathways and molecules have been identified in regulating drug-induced autophagy that impact the outcome of anticancer therapy, such as the PI3K-Akt-mTOR pathway, one of the main regulators of autophagy.…”

Section: Introductionmentioning

confidence: 99%

Combination of an Autophagy Inducer and an Autophagy Inhibitor: A Smarter Strategy Emerging in Cancer Therapy

Liu

Zhang

et al. 2020

Front. Pharmacol.

View full text Add to dashboard Cite

Autophagy is considered a cytoprotective function in cancer therapy under certain conditions and is a drug resistance mechanism that represents a clinical obstacle to successful cancer treatment and leads to poor prognosis in cancer patients. Because certain clinical drugs and agents in development have cytoprotective autophagy effects, targeting autophagic pathways has emerged as a potential smarter strategy for cancer therapy. Multiple preclinical and clinical studies have demonstrated that autophagy inhibition augments the efficacy of anticancer agents in various cancers. Autophagy inhibitors, such as chloroquine and hydroxychloroquine, have already been clinically approved, promoting drug combination treatment by targeting autophagic pathways as a means of discovering and developing more novel and more effective cancer therapeutic approaches. We summarize current studies that focus on the antitumor efficiency of agents that induce cytoprotective autophagy combined with autophagy inhibitors. Furthermore, we discuss the challenge and development of targeting cytoprotective autophagy as a cancer therapeutic approach in clinical application. Thus, we need to facilitate the exploitation of appropriate autophagy inhibitors and coadministration delivery system to cooperate with anticancer drugs. This review aims to note optimal combination strategies by modulating autophagy for therapeutic advantage to overcome drug resistance and enhance the effect of antitumor therapies on cancer patients.

show abstract

“…A good example of research on a marine-derived compound as possible autophagy modulators is the investigation of jaspine B and its 2-alkylaminomethyl derivatives performed by two different groups [ 80 , 81 ]. Jaspine B is an anhydrophytosphingosine that was first found in the marine sponge Pachastrissa sp.…”

Section: Marine Compounds With a Validated Autophagy-modulatory Efmentioning

confidence: 99%

“…This speculation, however, requires further validation [ 83 ]. Nevertheless, in the following research by Yu et al (Jin group), the authors have applied a number of diverse methods to prove the autophagy-inducing activity of the most promising jaspine B derivative called C-2 in human bladder cancer cells [ 80 ]. Thus, the authors successfully demonstrated the importance of JNK and Nrf2 pathways for the C-2-induced autophagy, which seems to be cytoprotective, in bladder cancer cells.…”

Section: Marine Compounds With a Validated Autophagy-modulatory Efmentioning

confidence: 99%

“…Thus, the authors successfully demonstrated the importance of JNK and Nrf2 pathways for the C-2-induced autophagy, which seems to be cytoprotective, in bladder cancer cells. Finally, the anticancer and autophagy-inducing activity as well as the mode of action of C-2 were validated in vivo using the nude mice xenografts [ 80 ]. The rather contradictive results of these two high-quality pieces of research performed by Cingolani et al [ 81 ] and Yu et al [ 80 ] could be explained by the different models used, namely, gastric [ 77 ] and bladder cancer cells [ 80 ], as well as by the chemical difference in the original natural jaspine B [ 81 ] and its synthetic derivative C-2 [ 80 ].…”

Section: Marine Compounds With a Validated Autophagy-modulatory Efmentioning

confidence: 99%

See 1 more Smart Citation

Blue-Print Autophagy in 2020: A Critical Review

Dyshlovoy

2020

Marine Drugs

View full text Add to dashboard Cite

Autophagy is an elegant and complex biological process that has recently attracted much attention from the scientific community. The compounds which are capable of control and modulation of this process have a promising potential as therapeutics for a number of pathological conditions, including cancer and neurodegenerative disorders. At the same time, due to the relatively young age of the field, there are still some pitfalls in the autophagy monitoring assays and interpretation of the experimental data. This critical review provides an overview of the marine natural compounds, which have been reported to affect autophagy. The time period from the beginning of 2016 to the middle of 2020 is covered. Additionally, the published data and conclusions based on the experimental results are re-analyzed with regard to the guidelines developed by Klionsky and colleagues (Autophagy. 2016; 12(1): 1–222), which are widely accepted by the autophagy research community. Remarkably and surprisingly, more than half of the compounds reported to be autophagy activators or inhibitors could not ultimately be assigned to either category. The experimental data reported for those substances could indicate both autophagy activation and inhibition, requiring further investigation. Thus, the reviewed molecules were divided into two groups: having validated and non-validated autophagy modulatory effects. This review gives an analysis of the recent updates in the field and raises an important problem of standardization in the experimental design and data interpretation.

show abstract

SP600125 enhances C-2-induced cell death by the switch from autophagy to apoptosis in bladder cancer cells

Cited by 31 publications

References 45 publications

β-Caryophyllene Inhibits Cell Proliferation through a Direct Modulation of CB2 Receptors in Glioblastoma Cells

β-Caryophyllene Inhibits Cell Proliferation through a Direct Modulation of CB2 Receptors in Glioblastoma Cells

Combination of an Autophagy Inducer and an Autophagy Inhibitor: A Smarter Strategy Emerging in Cancer Therapy

Blue-Print Autophagy in 2020: A Critical Review

Contact Info

Product

Resources

About