A <i>trans</i>-Pt(<scp>ii</scp>) hedgehog pathway inhibitor complex with cytotoxicity towards breast cancer stem cells and triple negative breast cancer cells

Ryan, Aoife A.; Northcote-Smith, Joshua; McKeon, Aoife M; Roe, Andrew J.; O’Dowd, Paul; Twamley, Brendan; Chonghaile, Tríona Ní; Suntharalingam, Kogularamanan; Griffith, Darren M.

doi:10.1039/d2dt02865d

Cited by 3 publications

(4 citation statements)

References 37 publications

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“…Complexes with bromocatechol (32)(33)(34) showed good cytotoxic activity against MDA-MB-231 cells, which were independent of the cyclometalated ligand's nature. Complexes 29-31, possessing alizarine as a ligand, were studied as a mixture of the two isomers, showing a different form of cytotoxic activity that depends on a different CˆN ligand.…”

Section: Ionic Pt(ii) Complexesmentioning

confidence: 97%

“…Another trans-conformation Pt(II) complex that can be used to overcome cisplatin resistance and its side effects is an inhibitor of the Hedgehog (Hh) pathway based on GANT61 (Figure 5) [33]. The Hedgehog signaling pathway regulates cell differentiation, cell proliferation, and stem cell maintenance during embryonic development, which results in the transcription of three glioma-associated oncogene homolog (GLI) transcription factor proteins: GLI1, GLI2, and GLI3.…”

Section: Pt(ii) Complexes In Trans Conformationmentioning

confidence: 99%

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The Challenging Treatment of Cisplatin-Resistant Tumors: State of the Art and Future Perspectives

et al. 2023

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One of the main problems in chemotherapy using platinum drugs as anticancer agents is the resistance phenomenon. Synthesizing and evaluating valid alternative compounds is challenging. This review focuses on the last two years of progress in the studies of platinum (II)- and platinum (IV)-based anticancer complexes. In particular, the research studies reported herein focus on the capability of some platinum-based anticancer agents to bypass resistance to chemotherapy, which is typical of well-known drugs such as cisplatin. Regarding platinum (II) complexes, this review deals with complexes in trans conformation; complexes containing bioactive ligands, as well as those that are differently charged, all experience a different reaction mechanism compared with cisplatin. Regarding platinum (IV) compounds, the focus was on complexes with biologically active ancillary ligands that exert a synergistic effect with platinum (II)-active complexes upon reduction, or those for which controllable activation can be realized thanks to intracellular stimuli.

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Section: Ionic Pt(ii) Complexesmentioning

confidence: 97%

Section: Pt(ii) Complexes In Trans Conformationmentioning

confidence: 99%

The Challenging Treatment of Cisplatin-Resistant Tumors: State of the Art and Future Perspectives

et al. 2023

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“…The non-canonical Hedgehog inhibitor Gli-antagonist 61 (GANT61) decreased the TNBC CSC population and enhanced paclitaxel efficacy in TNBC cells [ 103 ]. A trans-Pt (II) hedgehog pathway inhibitor complex reduced the number of CSC mammospheres formed [ 104 ].…”

Section: Therapies Targeting Cscs Plasticity In Tnbcmentioning

confidence: 99%

“…For example, vismodegib, a small-molecule inhibitor (SMI) that targets the Hedgehog pathway by binding to smoothened, has reduced the CSC population and sensitized TNBC cells to chemotherapy [48,102]. The non-canonical Hedgehog inhibitor Gli-antagonist 61 (GANT61) decreased the TNBC CSC population and enhanced paclitaxel efficacy in TNBC cells [103]. A trans-Pt (II) hedgehog pathway inhibitor complex reduced the number of CSC mammospheres formed [104].…”

Section: Inhibiting Signaling Pathways That Regulate Csc Plasticitymentioning

confidence: 99%

Targeting cancer stem cell plasticity in triple-negative breast cancer

Guo,

Han

2023

Exploration of Targeted Anti-Tumor Therapy

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Triple-negative breast cancer (TNBC) is a highly aggressive breast cancer subtype with limited treatment options. Cancer stem cells (CSCs) are thought to play a crucial role in TNBC progression and resistance to therapy. CSCs are a small subpopulation of cells within tumors that possess self-renewal and differentiation capabilities and are responsible for tumor initiation, maintenance, and metastasis. CSCs exhibit plasticity, allowing them to switch between states and adapt to changing microenvironments. Targeting CSC plasticity has emerged as a promising strategy for TNBC treatment. This review summarizes recent advances in understanding the molecular mechanisms underlying CSC plasticity in TNBC and discusses potential therapeutic approaches targeting CSC plasticity.

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Synthesis and anticancer mechanisms of four novel platinum(ii) 4′-substituted-2,2′:6′,2′′-terpyridine complexes

Liang,

Wu,

Huang

et al. 2024

Dalton Trans.

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A trans-Pt(ii) hedgehog pathway inhibitor complex with cytotoxicity towards breast cancer stem cells and triple negative breast cancer cells

Abstract: The first example of a Pt complex of GANT61, a hedgehog (Hh) pathway inhibitor is reported. Reaction of cis-[Pt(II)Cl2(dmso)2] with one equivalent of 4-pyridine carboxaldehyde (4-PCA, control ligand) or one...

Cited by 3 publications

References 37 publications

The Challenging Treatment of Cisplatin-Resistant Tumors: State of the Art and Future Perspectives

The Challenging Treatment of Cisplatin-Resistant Tumors: State of the Art and Future Perspectives

Targeting cancer stem cell plasticity in triple-negative breast cancer

Synthesis and anticancer mechanisms of four novel platinum(ii) 4′-substituted-2,2′:6′,2′′-terpyridine complexes

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