5 research outputs found
Cytotoxic Imidazolyl-Mesalazine Ester-Based Ru(II) Complexes Reduce Expression of Stemness Genes and Induce Differentiation of Oral Squamous Cell Carcinoma
The aggressiveness and recurrence of cancer is linked
to cancer
stem cells (CSCs), but drugs targeting CSCs may not succeed in the
clinic due to the lack of a distinct CSC subpopulation. Clinical Pt(II)
drugs can increase stemness. We screened 15 RuII or IrIII complexes with mesalazine or 3-aminobenzoate
Schiff bases of the general formulas [Ru(p-cym)L]+, [Ru(p-cym)L],
and [Ir(Cp*)L]+ (L = L1–L9) and found three complexes (2, 12, and 13) that are active against oral squamous cell carcinoma (OSCC)
CSCs. There is a putative oncogenic role of transcription factors
(viz. NOTCH1, SOX2, c-MYC) to enhance the stemness. Our work shows
that imidazolyl-mesalazine ester-based RuII complexes
inhibit growth of CSC-enriched OSCC 3D spheroids at low micromolar
doses (2 μM). Complexes 2, 12, and 13 reduce stemness gene expression and induce differentiation
markers (Involucrin, CK10) in OSCC
3D cultures. The imidazolyl-mesalazine ester-based RuII complex 13 shows the strongest effect. Downregulating
c-MYC suggests that RuII complexes may target c-MYC-driven
cancers
Cytotoxic Imidazolyl-Mesalazine Ester-Based Ru(II) Complexes Reduce Expression of Stemness Genes and Induce Differentiation of Oral Squamous Cell Carcinoma
The aggressiveness and recurrence of cancer is linked
to cancer
stem cells (CSCs), but drugs targeting CSCs may not succeed in the
clinic due to the lack of a distinct CSC subpopulation. Clinical Pt(II)
drugs can increase stemness. We screened 15 RuII or IrIII complexes with mesalazine or 3-aminobenzoate
Schiff bases of the general formulas [Ru(p-cym)L]+, [Ru(p-cym)L],
and [Ir(Cp*)L]+ (L = L1–L9) and found three complexes (2, 12, and 13) that are active against oral squamous cell carcinoma (OSCC)
CSCs. There is a putative oncogenic role of transcription factors
(viz. NOTCH1, SOX2, c-MYC) to enhance the stemness. Our work shows
that imidazolyl-mesalazine ester-based RuII complexes
inhibit growth of CSC-enriched OSCC 3D spheroids at low micromolar
doses (2 μM). Complexes 2, 12, and 13 reduce stemness gene expression and induce differentiation
markers (Involucrin, CK10) in OSCC
3D cultures. The imidazolyl-mesalazine ester-based RuII complex 13 shows the strongest effect. Downregulating
c-MYC suggests that RuII complexes may target c-MYC-driven
cancers