ArticleNaunyn-Schmiedeberg's archives of pharmacology2015
Zerumbone, a ginger sesquiterpene, induces apoptosis and autophagy in human hormone-refractory prostate cancers through tubulin binding and crosstalk between endoplasmic reticulum stress and mitochondrial insult.
Article in Naunyn-Schmiedeberg's archives of pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 51 citations in OpenAlex.
- CDC25C downregulation suppresses HCC growth via mitochondrial stress-induced autophagy and apoptosis.Scientific reports · 2026Article
- Effects of Ginger (Biomolecules · 2024Review
- Cell division cyclin 25C knockdown inhibits hepatocellular carcinoma development by inducing endoplasmic reticulum stress.World journal of gastroenterology · 2024Article
- Anticancer bioactivity of zerumbone on pediatric rhabdomyosarcoma cells.Journal of cancer research and clinical oncology · 2023Article
- Molecular Basis of Prostate Cancer and Natural Products as Potential Chemotherapeutic and Chemopreventive Agents.Frontiers in pharmacology · 2021Review
- Natural Products Targeting the Mitochondria in Cancers.Molecules (Basel, Switzerland) · 2020Review
- Nutraceutical Compounds as Sensitizers for Cancer Treatment in Radiation Therapy.International journal of molecular sciences · 2019Review
- A Tale of Two States: Normal and Transformed, With and Without Rigidity Sensing.Annual review of cell and developmental biology · 2019Review
- Gingers and Their Purified Components as Cancer Chemopreventative Agents.Molecules (Basel, Switzerland) · 2019Review
- Zerumbone, a cyclic sesquiterpene, exerts antimitotic activity in HeLa cells through tubulin binding and exhibits synergistic activity with vinblastine and paclitaxel.Cell proliferation · 2019Article
- Potential of Zerumbone as an Anti-Cancer Agent.Molecules (Basel, Switzerland) · 2019Review
- The Role of the ER-Induced UPR Pathway and the Efficacy of Its Inhibitors and Inducers in the Inhibition of Tumor Progression.Oxidative medicine and cellular longevity · 2019Review
- Anti-Cancer Natural Products and Their Bioactive Compounds Inducing ER Stress-Mediated Apoptosis: A Review.Nutrients · 2018Review
- Zerumbone Regulates DNA Repair Responding to Ionizing Radiation and Enhances Radiosensitivity of Human Prostatic Cancer Cells.Integrative cancer therapies · 2018Article
- A Review of the Biomedical Applications of Zerumbone and the Techniques for Its Extraction from Ginger Rhizomes.Molecules (Basel, Switzerland) · 2017Review
- Natural Compounds from Herbs that can Potentially Execute as Autophagy Inducers for Cancer Therapy.International journal of molecular sciences · 2017Review
- The sesquiterpene α-bisabolol in the adipocyte-cancer desmoplastic crosstalk: does it have an action on epithelial-mesenchymal transition mechanisms?International journal of clinical oncology · 2017Review
- Emerging Anti-Mitotic Activities and Other Bioactivities of Sesquiterpene Compounds upon Human Cells.Molecules (Basel, Switzerland) · 2017Review
- The Natural Occurring Compounds Targeting Endoplasmic Reticulum Stress.Evidence-based complementary and alternative medicine : eCAM · 2016Review
- Possible Anticancer Mechanisms of Some Costus speciosus Active Ingredients Concerning Drug Discovery.Current drug discovery technologies · 2016Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Zerumbone, a natural monocyclic sesquiterpene, is the main component of the tropical plant Zingiber zerumbet Smith. Zerumbone induced antiproliferative and apoptotic effects against PC-3 and DU-145, two human hormone-refractory prostate cancer (HRPC) cell lines. Zerumbone inhibited microtubule assembly and induced an increase of MPM-2 expression (specific recognition of mitotic proteins). It also caused an increase of phosphorylation of Bcl-2 and Bcl-xL, two key events in tubulin-binding effect, indicating tubulin-binding capability and mitotic arrest to zerumbone action. Furthermore, zerumbone induced several cellular effects distinct from tubulin-binding properties. First, zerumbone significantly increased, while paclitaxel (as a tubulin-binding control) decreased, Mcl-1 protein expression. Second, paclitaxel but not zerumbone induced Cdk1 activity. Third, zerumbone other than paclitaxel induced Cdc25C downregulation. The data suggest that, in addition to targeting tubulin/microtubule, zerumbone may act on other targets for signaling transduction. Zerumbone induced mitochondrial damage and endoplasmic reticulum (ER) stress as evidenced by the loss of mitochondrial membrane potential and upregulation of GRP-78 and CHOP/GADD153 expression. Zerumbone induced an increase of intracellular Ca(2+) levels, a crosstalk marker between ER stress and mitochondrial insult, associated with the formation of active calpain I fragment. It induced apoptosis through a caspase-dependent way and caused autophagy as evidenced by dramatic LC3-II formation. In summary, the data suggest that zerumbone is a multiple targeting compound that inhibits tubulin assembly and induces a crosstalk between ER stress and mitochondrial insult, leading to apoptosis and autophagy in HRPCs.
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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.