ArticleOncotarget2015
Synergistic anticancer effect of cisplatin and Chal-24 combination through IAP and c-FLIPL degradation, Ripoptosome formation and autophagy-mediated apoptosis.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- Dual targeting of BCL-XL and MCL-1 exposes a rapid and exploitable apoptotic vulnerability in non-small cell lung cancer.Cell death and differentiation · 2026Article
- Chalcones as multitarget modulators in non-small cell lung cancer: mechanistic insights and therapeutic perspectives.Archives of toxicology · 2026Review
- Exploiting spirooxindoles for dual DNA targeting/CDK2 inhibition and simultaneous mitigation of oxidative stress towards selective NSCLC therapy; synthesis, evaluation, and molecular modelling studies.RSC medicinal chemistry · 2024Article
- Article
- Autophagy modulating agents as chemosensitizers for cisplatin therapy in cancer.Investigational new drugs · 2021Review
- ERK Activation-Mediated Autophagy Induction Resists Licochalcone A-Induced Anticancer Activities in Lung Cancer CellsOncoTargets and therapy · 2020Article
- Metformin induces apoptotic cytotoxicity depending on AMPK/PKA/GSK-3β-mediated c-FLIPCancer management and research · 2019Article
- Ameliorative effects of rutin against cisplatin-induced reproductive toxicity in male rats.BMC urology · 2018Article
- 3-Oxoacid CoA transferase 1 as a therapeutic target gene for cisplatin-resistant ovarian cancer.Oncology letters · 2018Article
- Ophiopogonin B sensitizes TRAIL-induced apoptosis through activation of autophagy flux and downregulates cellular FLICE-like inhibitory protein.Oncotarget · 2018Article
- Induction Effect to Apoptosis by Maitake Polysaccharide: Synergistic Effect of Its Combination With Vitamin C in Neuroglioma Cell.Journal of evidence-based complementary & alternative medicine · 2017Article
- Chalcone: A Privileged Structure in Medicinal Chemistry.Chemical reviews · 2017Review
- Smac mimetic LCL161 overcomes protective ER stress induced by obatoclax, synergistically causing cell death in multiple myeloma.Oncotarget · 2016Article
- TR4 nuclear receptor enhances the cisplatin chemo-sensitivity via altering the ATF3 expression to better suppress HCC cell growth.Oncotarget · 2016Article
- Autophagy-Mediated Degradation of IAPs and c-FLIP(L) Potentiates Apoptosis Induced by Combination of TRAIL and Chal-24.Journal of cellular biochemistry · 2016Article
- Whole exome sequencing identifies novel candidate genes that modify chronic obstructive pulmonary disease susceptibility.Human genomics · 2016Article
- Suppression of mTOR pathway and induction of autophagy-dependent cell death by cabergoline.Oncotarget · 2015Article
- Autophagy and apoptosis in liver injury.Cell cycle (Georgetown, Tex.) · 2015Review
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Drug resistance is a major hurdle in anticancer chemotherapy. Combined therapy using drugs with distinct mechanisms of function may increase anticancer efficacy. We have recently identified the novel chalcone derivative, chalcone-24 (Chal-24), as a potential therapeutic that kills cancer cells through activation of an autophagy-mediated necroptosis pathway. In this report, we investigated if Chal-24 can be combined with the frontline genotoxic anticancer drug, cisplatin for cancer therapy. The combination of Chal-24 and cisplatin synergistically induced apoptotic cytotoxicity in lung cancer cell lines, which was dependent on Chal-24-induced autophagy. While cisplatin slightly potentiated the JNK/Bcl2/Beclin1 pathway for autophagy activation, its combination with Chal-24 strongly triggered proteasomal degradation of the cellular inhibitor of apoptosis proteins (c-IAPs) and formation of the Ripoptosome complex that contains RIP1, FADD and caspase 8. Furthermore, the cisplatin and Chal-24 combination induced dramatic degradation of cellular FLICE (FADD-like IL-1β-converting enzyme)-inhibitory protein large (cFLIPL) which suppresses Ripoptosome-mediated apoptosis activation. These results establish a novel mechanism for potentiation of anticancer activity with the combination of Chal-24 and cisplatin: to enhance apoptosis signaling through Ripoptosome formation and to release the apoptosis brake through c-FLIPL degradation. Altogether, our work suggests that the combination of Chal-24 and cisplatin could be employed to improve chemotherapy efficacy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.