Indisulam exerts anticancer effects via modulation of transcription, translation and alternative splicing on human cervical cancer cells.

Indisulam is a synthetic sulfonamides drug with anticancer activity in various tumors. However, the effect and molecular mechanism of indisulam have still not been studied in human cervical cancer. We treated human cervical cancer cell lines (HeLa and C33A) with indisulam, evaluated its efficacy, and investigated its molecular targets. Indisulam inhibited tumor growth and induced RBM39 degradation in a dose-dependent manner. RNA-seq and proteomics analysis revealed that indisulam disrupted transcriptional regulation pathways related to mRNA splicing and apoptosis. More importantly, indisulam caused mis-splicing of RNA transcripts including p73 isoforms ΔNp73 and TAp73 which have opposite roles in apoptosis regulation. Indisulam increased TAp73 expression and triggered mitochondrial apoptosis independent of p53 status in HeLa cells. In summary, our data suggests that indisulam has therapeutic potential in cervical cancer, representing an attractive strategy in p53-disrupted cancers and should be further investigated.