ArticlePloS one2012
Spirooxindole derivative SOID-8 induces apoptosis associated with inhibition of JAK2/STAT3 signaling in melanoma cells.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 33 citations in OpenAlex.
- Spirooxindole Derivatives as Emerging Scaffolds in Drug Discovery: Synthetic Strategies, Structure-Activity Relationship, and Biological Activities.ChemMedChem · 2026Review
- Naturally derived indole alkaloids targeting regulated cell death (RCD) for cancer therapy: from molecular mechanisms to potential therapeutic targets.Journal of hematology & oncology · 2022Review
- Design of Novel Enantiopure Dispirooxindolopyrrolidine-Piperidones as Promising Candidates toward COVID-19: Asymmetric Synthesis, Crystal Structure andMolecules (Basel, Switzerland) · 2022Article
- RLIP depletion induces apoptosis associated with inhibition of JAK2/STAT3 signaling in melanoma cells.Carcinogenesis · 2021Article
- Targeting STAT3 in Cancer Immunotherapy.Molecular cancer · 2020Review
- Signal transducer and activator of transcription-3 drives the high-fat diet-associated prostate cancer growth.Cell death & disease · 2019Article
- STAT3 enhances the constitutive activity of AGC kinases in melanoma by transactivating PDK1.Cell & bioscience · 2019Article
- Context-dependent miR-204 and miR-211 affect the biological properties of amelanotic and melanotic melanoma cells.Oncotarget · 2017Article
- MLS-2384, a new 6-bromoindirubin derivative with dual JAK/Src kinase inhibitory activity, suppresses growth of diverse cancer cells.Cancer biology & therapy · 2014Article
- A facile synthesis of functionalized dispirooxindole derivatives via a three-component 1,3-dipolar cycloaddition reaction.Molecules (Basel, Switzerland) · 2013Article
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Melanoma is generally refractory to current chemotherapy, thus new treatment strategies are needed. In this study, we synthesized a series of spirooxindole derivatives (SOID-1 to SOID-12) and evaluated their antitumor effects on melanoma. Among the 12 spirooxindole derivatives, SOID-8 showed the strongest antitumor activity by viability screening. SOID-8 inhibited viability of A2058, A375, SK-MEL-5 and SK-MEL-28 human melanoma cells in a dose- and time-dependent manner. SOID-8 also induced apoptosis of these tumor cells, which was confirmed by positive Annexin V staining and an increase of poly(ADP-ribose) polymerase cleavage. The antiapoptotic protein Mcl-1, a member of the Bcl-2 family, was downregulated and correlated with SOID-8 induced apoptosis. In addition, SOID-8 reduced tyrosine phosphorylation of Signal Tansducer and Activator of Transcription 3 (STAT3) in both dose- and time-dependent manners. This inhibition was associated with decreased levels of phosphorylation of Janus-activated kinase-2 (JAK2), an upstream kinase that mediates STAT3 phosphorylation at Tyr705. Accordingly, SOID-8 inhibited IL-6-induced activation of STAT3 and JAK2 in melanoma cells. Finally, SOID-8 suppressed melanoma tumor growth in a mouse xenograft model, accompanied with a decrease of phosphorylation of JAK2 and STAT3. Our results indicate that the antitumor activity of SOID-8 is at least partially due to inhibition of JAK2/STAT3 signaling in melanoma cells. These findings suggest that the spirooxindole derivative SOID-8 is a promising lead compound for further development of new preventive and therapeutic agents for melanoma.
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