ArticleCancer science2014
High antitumor activity of pladienolide B and its derivative in gastric cancer.
Article in Cancer science, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 52 citations in OpenAlex.
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- The Role of Splicing Machinery as a Promising Potential Therapeutic Target for Pituitary Neuroendocrine Tumors (PitNETs).Cancers · 2026Review
- Synergistic effect of Pladienolide B and cisplatin: enhancing autophagy in hepatoma cells through the AMPK/mTOR/ULK1 pathway.Cell death discovery · 2026Article
- Low-risk MDS-A spotlight on precision medicine forHemaSphere · 2025Review
- Pogo transposons provide tools to restrict cancer growth.Molecular oncology · 2025Article
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- PHF5A as a new OncoTarget and therapeutic prospects.Heliyon · 2023Review
- Alternative mRNA Splicing and Promising Therapies in Cancer.Biomolecules · 2023Review
- In Vivo Acute Toxicity Studies of Novel Anti-Melanoma Compounds Downregulators of hnRNPH1/H2.Biomolecules · 2023Article
- Research progress and therapeutic prospect of PHF5A acting as a new target for malignant tumors.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2022Review
- Nuclear RNA binding regulates TDP-43 nuclear localization and passive nuclear export.Cell reports · 2022Article
- Therapeutic Targeting of Alternative Splicing: A New Frontier in Cancer Treatment.Frontiers in oncology · 2022Review
- Therapeutic Targeting of Alternative RNA Splicing in Gastrointestinal Malignancies and Other Cancers.International journal of molecular sciences · 2021Review
- Genetic landscape of T cells identifies synthetic lethality for T-ALL.Communications biology · 2021Article
- Spliceosome-regulated RSRP1-dependent NF-κB activation promotes the glioblastoma mesenchymal phenotype.Neuro-oncology · 2021Article
- Total Syntheses of Pladienolide-Derived Spliceosome Modulators.Molecules (Basel, Switzerland) · 2021Review
- Splicing factors control triple-negative breast cancer cell mitosis through SUN2 interaction and sororin intron retention.Journal of experimental & clinical cancer research : CR · 2021Article
- Prostate cancer racial, socioeconomic, geographic disparities: targeting the genomic landscape and splicing events in search for diagnostic, prognostic and therapeutic targets.American journal of cancer research · 2021Review
- Splicing factor SF3B1 promotes endometrial cancer progression via regulating KSR2 RNA maturation.Cell death & disease · 2020Article
- Apoptosis induction and cell cycle arrest of pladienolide B in erythroleukemia cell lines.Investigational new drugs · 2020Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The antitumor activity of pladienolide B, a novel splicing inhibitor, against gastric cancer is totally unknown and no predictive biomarker of pladienolide B efficacy has been reported. We investigated the antitumor activity of pladienolide B and its derivative on gastric cancer cell lines and primary cultured cancer cells from carcinomatous ascites of gastric cancer patients. The effect of pladienolide B and its derivative on six gastric cancer cell lines was investigated using a MTT assay and the mean IC50 values determined to be 1.6 ± 1.2 (range, 0.6-4.0) and 1.2 ± 1.1 (range, 0.4-3.4) nM, respectively, suggesting strong antitumor activity against gastric cancer. The mean IC50 value of pladienolide B derivative against primary cultured cells from 12 gastric cancer patients was 4.9 ± 4.7 nM, indicative of high antitumor activity. When 18 SCID mice xenografted with primary cultured cells from three patients were administered the pladienolide B derivative intraperitoneally, all tumors completely disappeared within 2 weeks after treatment. Histological examination revealed a pathological complete response for all tumors. In the xenograft tumors after treatment with pladienolide B derivative, immature mRNA were detected and apoptotic cells were observed. When the expressions of cell-cycle proteins p16 and cyclin E in biopsied gastric cancer specimens were examined using immunohisctochemistry, positivities for p16 and cyclin E were significantly and marginally higher, respectively, in the low-IC50 group compared with the high-IC50 group, suggesting the possibility that they might be useful as predictive biomarkers for pladienolide B. In conclusion, pladienolide B was very active against gastric cancer via a mechanism involving splicing impairment and apoptosis induction.
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Registered trials
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