Monofunctional dimetallic Ru(η6-arene) complexes inhibit NOTCH1 signaling pathway and synergistically enhance anticancer effect in combination with cisplatin or vitamin C

Cytotoxic Imidazolyl-Mesalazine Ester-Based Ru(II) Complexes Reduce Expression of Stemness Genes and Induce Differentiation of Oral Squamous Cell Carcinoma

“…The investigation was carried out against oral squamous cell carcinoma (OSCC) since it has a major occurrence in the Southeast Asian subcontinent, yet development of new drugs for OSCC is scarce. − Potential involvement of CSCs in oral tumor initiation and progression shows a 5-year survival rate of around 50% . The low survival rate is due to recurrence as a result of heterogeneity among cancer cells including CSCs. − CSCs exhibit deregulation of Notch, Wnt, or Hedgehog pathways; hence, inhibiting these pathways presents a viable option to kill CSCs. ,, Our investigation monitored the Notch pathway and the common checkpoints of stemness via the three pathways (Figure ).…”

“…Notch pathway is developmentally conserved for cell fate determination, proliferation, differentiation, and stem cell maintenance. , Studies show the putative oncogenic role of the active Notch pathway in oral cancers. − Blocking NOTCH1 decreases cell proliferation, 3D sphere growth, and xenograft formation by oral cancer cells. , Possibly due to the anti-apoptotic property of activated NOTCH, − activation of the Notch pathway is responsible for cisplatin-induced activation of stemness and drug resistance in oral cancer. , Thus, metal complexes that can efficiently kill the stem cells of OSCC overexpressing NOTCH1 should pave a new pathway for developing metal-based chemotherapeutic agents. Recently, an ONS donor ligand-based dinuclear Ru­(η 6 -arene) complex showed CSC killing ability, and Western blot studies showed that the complex decreases the expression of Notch1 …”