Biopharmacological considerations for accelerating drug development of deguelin, a rotenoid with potent chemotherapeutic and chemopreventive potential.

Abstract:

:Deguelin is a rotenoid compound that exists in abundant quantities in the bark, roots, and leaves of the Leguminosae family of plants. An analysis of evidence from both in vitro and in vivo studies suggests that deguelin displays potent anticancer activity against multiple cancer types and exhibits chemopreventive potential in Akt-inducible transgenic mouse models. Deguelin appears to impede carcinogenesis by enhancing cell apoptosis and hindering malignant transformation and tumor cell propagation. Crucial oncogenic pathways likely targeted by deguelin include the epithelial-to-mesenchymal transition; angiogenesis-related pathways; and the phosphoinositide 3-kinase/Akt, Wnt, epidermal growth factor receptor, c-Met, and hedgehog signal transduction cascades. This review article provides a comprehensive summary of current preclinical research featuring deguelin as a leading chemotherapeutic and chemopreventive compound, and it highlights the importance of identifying companion molecular biomarkers and performing systemic pharmacokinetic studies for accelerating the process of developing deguelin as a clinical anticancer agent.

journal_name

Cancer

journal_title

Cancer

authors

Varughese RS,Lam WS,Marican AABH,Viganeshwari SH,Bhave AS,Syn NL,Wang J,Wong AL,Kumar AP,Lobie PE,Lee SC,Sethi G,Goh BC,Wang L

doi

10.1002/cncr.32069

subject

Has Abstract

pub_date

2019-06-01 00:00:00

pages

1789-1798

issue

11

eissn

0008-543X

issn

1097-0142

journal_volume

125

pub_type

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