ArticleMolecular pharmacology2013
Cucurbitacin I inhibits Rac1 activation in breast cancer cells by a reactive oxygen species-mediated mechanism and independently of Janus tyrosine kinase 2 and P-Rex1.
Article in Molecular pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 43 citations in OpenAlex.
- VAV2 Drives EGFR-Mediated Rac1 Responses in Prostate Cancer.Molecular cancer research : MCR · 2025Article
- Cucurbitacin I inhibits the proliferation of pancreatic cancer through the JAK2/STAT3 signalling pathwayJournal of Cancer · 2022Article
- Evaluation of active Rac1 levels in cancer cells: A case of misleading conclusions from immunofluorescence analysis.The Journal of biological chemistry · 2020Article
- Article
- Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine.Chinese medicine · 2019Review
- Identification of 16,25-Royal Society open science · 2018Article
- Redox regulation of the actin cytoskeleton and its role in the vascular system.Free radical biology & medicine · 2017Review
- Fluctuation of ROS regulates proliferation and mediates inhibition of migration by reducing the interaction between DLC1 and CAV-1 in breast cancer cells.In vitro cellular & developmental biology. Animal · 2017Article
- Characterization of a P-Rex1 gene signature in breast cancer cells.Oncotarget · 2016Article
- Heregulin/ErbB3 Signaling Enhances CXCR4-Driven Rac1 Activation and Breast Cancer Cell Motility via Hypoxia-Inducible Factor 1α.Molecular and cellular biology · 2016Article
- Flavone inhibits migration through DLC1/RhoA pathway by decreasing ROS generation in breast cancer cells.In vitro cellular & developmental biology. Animal · 2016Article
- Low nanomolar concentrations of Cucurbitacin-I induces G2/M phase arrest and apoptosis by perturbing redox homeostasis in gastric cancer cells in vitro and in vivo.Cell death & disease · 2016Article
- PKCε Is an Essential Mediator of Prostate Cancer Bone Metastasis.Molecular cancer research : MCR · 2015Article
- JSI124 inhibits breast cancer cell growth by suppressing the function of B cells via the downregulation of signal transducer and activator of transcription 3.Oncology letters · 2014Article
- Transcriptional regulation of oncogenic protein kinase Cϵ (PKCϵ) by STAT1 and Sp1 proteins.The Journal of biological chemistry · 2014Article
- VASP activation via the Gα13/RhoA/PKA pathway mediates cucurbitacin-B-induced actin aggregation and cofilin-actin rod formation.PloS one · 2014Article
- Piperlongumine inhibits migration of glioblastoma cells via activation of ROS-dependent p38 and JNK signaling pathways.Oxidative medicine and cellular longevity · 2014Article
- Rho GTPases, oxidation, and cell redox control.Small GTPases · 2014Review
- Cucurbitacin covalent bonding to cysteine thiols: the filamentous-actin severing protein Cofilin1 as an exemplary target.Cell communication and signaling : CCS · 2013Article
- The roles of PIKE in tumorigenesis.Acta pharmacologica Sinica · 2013Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The small GTPase Rac1 has been widely implicated in mammary tumorigenesis and metastasis. Previous studies established that stimulation of ErbB receptors in breast cancer cells activates Rac1 and enhances motility via the Rac-guanine nucleotide exchange factor P-Rex1. As the Janus tyrosine kinase 2 (Jak2)/signal transducer and activator of transcription 3 (Stat3) pathway has been shown to be functionally associated with ErbB receptors, we asked if this pathway could mediate P-Rex1/Rac1 activation in response to ErbB ligands. Here we found that the anticancer agent cucurbitacin I, a Jak2 inhibitor, reduced the activation of Rac1 and motility in response to the ErbB3 ligand heregulin in breast cancer cells. However, Rac1 activation was not affected by Jak2 or Stat3 RNA interference, suggesting that the effect of cucurbitacin I occurs through a Jak2-independent mechanism. Cucurbitacin I also failed to affect the activation of P-Rex1 by heregulin. Subsequent analysis revealed that cucurbitacin I strongly activates RhoA and the Rho effector Rho kinase (ROCK) in breast cancer cells and induces the formation of stress fibers. Interestingly, disruption of the RhoA-ROCK pathway prevented the inhibitory effect of cucurbitacin I on Rac1 activation by heregulin. Lastly, we found that RhoA activation by cucurbitacin I is mediated by reactive oxygen species (ROS). The ROS scavenger N-acetyl L-cysteine and the mitochondrial antioxidant Mito-TEMPO rescued the inhibitory effect of cucurbitacin I on Rac1 activation. In conclusion, these results indicate that ErbB-driven Rac1 activation in breast cancer cells proceeds independently of the Jak2 pathway. Moreover, they established that the inhibitory effect of cucurbitacin I on Rac1 activity involves the alteration of the balance between Rho and Rac.
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