Synthetic analogues of marine alkaloid clathrodin differently induce phosphatidylserine exposure in monocytic cancer cells then in cancer stem cell lines

Nabergoj, Dominik; Vrbek, Sanja; Zidar, Nace; Tomašič, Tihomir; Kikelj, D.; Mašič, Lucija Peterlin; Muller, Christian D.

doi:10.1039/c6md00163g

Cited by 3 publications

(1 citation statement)

References 26 publications

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“…Clathrodin analogues induced apoptosis in pancreatic and testis cancer stem cell lines, but the mechanisms by which this is mediated are unclear. [77] G2.2, a sulfated non-saccharide GAG mimetic, could selectively inhibit colon and pancreatic CSCs through induction of apoptosis and attenuation of self-renewal capacity, [78] possibly through a mechanism inhibiting BMI-1 and c-MYC. Interestingly, a group of iron chelating small molecules had been shown to exhibit antiproliferative effects on cancer stem cells in vitro [79] and some selectivity for CSCs over normal cancer cells was reported with these small molecules.…”

Section: Miscellaneousmentioning

confidence: 99%

Targeting Cancer Stem Cells with Small Molecules

Müller

Cañeque

Acevedo

et al. 2017

Israel Journal of Chemistry

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Cancers arise as a result of physiological imbalances and subsequent uncontrolled cell division. Cancer initiation requires a set of biochemical alterations, including some occurring at the genetic and epigenetic levels. Thus, tumors are heterogeneous in nature making it challenging to selectively target different cancer cells by means of small molecule intervention. The paradigm of cancer stem cells (CSCs) describes subpopulations of cells with high selfrenewal and tumor-seeding capacity. These cells, typically refractory to conventional therapies, can give rise to relapse after treatment. Combinatorial strategies, including drugs that selectively target this population of cells, have emerged in recent years. Here, we review how discovery-basedunbiased -screening approaches [1] have helped identify small molecules that specifically target CSCs. We also highlight biological pathways characteristic of CSCs that can potentially be selectively targeted in a hypothesis-driven manner by small molecules. We describe molecules that effectively target CSCs and emphasize what is known about their biological modes of action. The diversity and complexity of biochemical processes that CSCs may be addicted to, raises the question of how selective targeting of these pathways can be achieved. This challenge may be addressed by the continuing production of structurally complex and diverse small molecules using target and diversity-oriented synthesis approaches.[2]

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Section: Miscellaneousmentioning

confidence: 99%