Natural Products Inspired Modulators of Cancer Stem Cells-specific Signaling Pathways Notch and Hedgehog

Author(s): Rocco Palermo, Francesca Ghirga, Maria Grazia Piccioni, Flavia Bernardi, Nadezda Zhdanovskaya, Paola Infante*, Mattia Mori*.

Journal Name: Current Pharmaceutical Design

Volume 24 , Issue 36 , 2018

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Abstract:

It is nowadays widely accepted that some tumors have a niche of cells endowed with stemness features, which may cause resistance to conventional anticancer therapies and relapse/recurrence of the malignancy. These cells are usually referred to as cancer stem cells (CSCs) and, different from normal cancer cells, are rather quiescent. Targeting CSCs is thus a highly challenging but promising strategy to counteract tumor growth, and to develop innovative anticancer agents.

Here, we review the chemical, biological and multidisciplinary efforts that have been spent in targeting CSCsspecific signaling pathways Notch and Hedgehog (Hh) for anticancer drug discovery. In particular, the use of natural products as a valuable source of lead compounds or chemical biology tools is emphasized. Examples of natural products functionalization through semi-synthetic transformations or total syntheses, aimed at improving pharmacokinetics and/or pharmacodynamics properties of natural products in Notch or Hh inhibition, are provided as well.

Keywords: Cancer, cancer stem cells, natural products, drug discovery, Notch, Hedgehog, inhibitors.

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Article Details

VOLUME: 24
ISSUE: 36
Year: 2018
Page: [4251 - 4269]
Pages: 19
DOI: 10.2174/1381612825666190111124822
Price: $58

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