ArticleCell communication and signaling : CCS2015
Homoharringtonine, a clinically approved anti-leukemia drug, sensitizes tumor cells for TRAIL-induced necroptosis.
Article in Cell communication and signaling : CCS, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 39 citations in OpenAlex.
- Necroptosis-related diseases are regulated by the unfolded protein response during endoplasmic reticulum stress.Genes & diseases · 2027Review
- Homoharringtonine: mechanisms, clinical applications and research progress.Frontiers in oncology · 2025Review
- Immunogenic cell death in cancer: targeting necroptosis to induce antitumour immunity.Nature reviews. Cancer · 2024Review
- Deregulation of New Cell Death Mechanisms in Leukemia.Cancers · 2024Review
- Necroptosis pathways in tumorigenesis.Seminars in cancer biology · 2022Review
- Combined Anti-Cancer Effects of Platycodin D and Sorafenib on Androgen-Independent and PTEN-Deficient Prostate Cancer.Frontiers in oncology · 2021Article
- Review
- Sophoridine exerts tumor-suppressive activities via promoting ESRRG-mediated β-catenin degradation in gastric cancer.BMC cancer · 2020Article
- Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition).European journal of immunology · 2019Article
- Heterogeneous intracellular TRAIL-receptor distribution predicts poor outcome in breast cancer patients.Journal of molecular medicine (Berlin, Germany) · 2019Article
- Bypassing drug resistance by triggering necroptosis: recent advances in mechanisms and its therapeutic exploitation in leukemia.Journal of experimental & clinical cancer research : CR · 2018Review
- Anticancer Activity of Natural Compounds from Plant and Marine Environment.International journal of molecular sciences · 2018Review
- Underwater Leidenfrost nanochemistry for creation of size-tailored zinc peroxide cancer nanotherapeutics.Nature communications · 2017Article
- PEGylated long-circulating liposomes deliver homoharringtonine to suppress multiple myeloma cancer stem cells.Experimental biology and medicine (Maywood, N.J.) · 2017Article
- Differences and Similarities in TRAIL- and Tumor Necrosis Factor-Mediated Necroptotic Signaling in Cancer Cells.Molecular and cellular biology · 2016Article
- Article
- Necroptosis in tumorigenesis, activation of anti-tumor immunity, and cancer therapy.Oncotarget · 2016Review
- Cancer and necroptosis: friend or foe?Cellular and molecular life sciences : CMLS · 2016Review
- An outline of necrosome triggers.Cellular and molecular life sciences : CMLS · 2016Review
- Cancer therapy in the necroptosis era.Cell death and differentiation · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundOne hallmark of cancer cells is their ability to evade physiologic signals causing regulated cell death (RCD). Correspondingly, TRAIL-based therapies to eliminate human cancer cells via enforced induction of apoptosis have been established and represent a promising approach in anti-cancer research. However, due to frequently appearing intrinsic or acquired resistances of tumor cells against apoptosis, TRAIL-based apoptotic strategies for the treatment of cancer patients have shown limited efficacy. As a potential alternative, regulated necrosis (and necroptosis triggered e.g. by TRAIL receptors 1/2) has recently gained considerable attention. Regulated necrosis represents a mode of RCD molecularly distinct from apoptosis whose potential in anti-cancer therapy is almost uncharacterized. Since in most cancer cells survival pathways counteract the effects of TRAIL-induced RCD, sensitizers such as cycloheximide (CHX) are frequently added in cell culture to overcome this problem. Unfortunately, those sensitizers are cytotoxic and therefore not suitable for the treatment of cancer patients. Here, we have alternatively employed homoharringtonine (HHT), a plant alkaloid which was recently approved by the U. S. Food and Drug Administration to treat patients with chronic myeloid lymphoma.
resultsWe show that HHT is an efficient sensitizer for TRAIL-induced necroptosis in multiple human cancer cell lines. In addition, HHT-enhanced TRAIL-mediated necroptosis occurs via the same signaling pathways (involving RIPK1/RIPK3/MLKL) as CHX-enhanced necroptosis. Importantly, consecutive treatment schedules of necroptosis and apoptosis in either combination revealed remarkable additive effects not reached by repetitive apoptotic treatments alone.
conclusionsTaken together, our data demonstrate that HHT can replace harmful substances such as CHX to sensitize human cancer cells to TRAIL-induced necroptosis. Thus, HHT represents a promising enhancer in TRAIL-based necroptotic anti-cancer therapies also in patients.
Indexed as
Identifiers
What OpenQuestion holds
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.