CUDC-101

1. Glioblastoma Cell Lines^[1]

Cell Viability Inhibition

In experiments with glioblastoma cell lines (U251, T98G, U87MG), CUDC-101 exhibited dose-dependent cytotoxicity. For instance, in U251 cells, the half-maximal inhibitory concentration (IC50) was approximately 0.5 μM after 72 hours of treatment, as measured by MTT assay. Similar IC50 values were observed in T98G (0.6 μM) and U87MG (0.7 μM) cells under the same conditions.

Migration Inhibition

Wound healing assays showed that CUDC-101 at 1 μM reduced cell migration by 45% in U251 cells compared to untreated controls after 24 hours.

Molecular Effects

Western blot analysis revealed a 3-fold increase in acetylated histone H3 levels and a 50% reduction in EGFR expression in U251 cells treated with 1 μM CUDC-101 for 24 hours.

2. Multiple Myeloma Cell Lines^[2]

Proliferation Inhibition

In RPMI-8226 multiple myeloma cells, CUDC-101 inhibited proliferation with an IC50 of 0.32 μM after 48 hours, as determined by CellTiter-Glo assay. In U266 cells, the IC50 was slightly higher at 0.45 μM.

Apoptosis Induction

Flow cytometry with Annexin V/PI staining showed that 1 μM CUDC-101 induced apoptosis in 38% of RPMI-8226 cells after 24 hours, increasing to 62% when combined with 10 nM bortezomib.

Cell Cycle Arrest

Treatment with 0.5 μM CUDC-101 for 24 hours increased the G2/M phase population from 15% (control) to 42% in RPMI-8226 cells, as assessed by propidium iodide staining and flow cytometry.

3. Triple-Negative Breast Cancer Cell Lines^[3]

Radiosensitization

In MDA-MB-231 cells, pretreatment with 0.5 μM CUDC-101 for 24 hours followed by 4 Gy X-ray irradiation reduced clonogenic survival by 60% compared to irradiation alone (surviving fraction: 0.15 vs. 0.38). For proton irradiation (4 Gy), the surviving fraction dropped to 0.10.

DNA Damage Repair Inhibition

Immunofluorescence staining for γ-H2AX foci showed that 1 μM CUDC-101 increased persistent DNA double-strand breaks, with an average of 25 foci per nucleus at 24 hours post-irradiation, compared to 8 foci in untreated irradiated controls.

Apoptosis

Caspase-3/7 activity assays indicated a 2.5-fold increase in apoptosis in MDA-MB-231 cells treated with 1 μM CUDC-101 plus 4 Gy X-ray compared to irradiation alone after 48 hours.

1. Chandler, R., et al. (2024). "Investigating CUDC-101 effect and mechanism of action against glioblastoma in vitro." Neuro-Oncology, 26(Supplement_7), vii16. [PMID pending; search PubMed for latest indexing]
2. Lai, C.-J., et al. (2023). "CUDC-101 as a dual-target inhibitor of EGFR and HDAC enhances the anti-myeloma effects of bortezomib by regulating G2/M cell cycle arrest." Journal of Zhejiang University-SCIENCE B, 24(5), 442–454. [PMID: 37190893]
3. Naidu, S., et al. (2024). "Multi-target inhibitor CUDC-101 impairs DNA damage repair and enhances radiation response in triple-negative breast cell line." Pharmaceuticals, 17(11), 1467. [PMID: 39176050]