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.

Plants in the Genus Tephrosia: Valuable Resources for Botanical Insecticides

“…Interestingly, it has been known that plants containing high deguelin have been used as an anthelmintic agent in certain regions of China [ 113 ] and as a traditional Thai medicine to treat hepatitis and hepatic dysfunction [ 114 ]. Recently, deguelin has been shown to have potent anticancer activity against multiple cancer types and can impede carcinogenesis by enhancing cell apoptosis and preventing malignant transformation and tumor proliferation [ 115 ]. Tephrosia species or chemotypes with high deguelin contents but low levels of rotenone could be ideal plant materials for developing botanical insecticides.…”

“…Current data indicate that deguelin could be equal to or more important than rotenone in pest management. Deguelin has been widely used as pharmaceutical compounds [ 115 ], its use as an insecticide may be environmentally more benign than rotenone. Thus, the potential of deguelin deserves future investigation.…”

Deguelin suppresses non-small cell lung cancer by inhibiting EGFR signaling and promoting GSK3β/FBW7-mediated Mcl-1 destabilization

“…Accumulating evidence reveals that the natural product deguelin exhibits profound anti-cancer potentials in multiple human cancer models, including lung cancer 14 , hepatocellular carcinoma 15 , colorectal cancer 16 , esophageal carcinoma 17 , metastatic melanoma 18 , and breast cancer 19 . The molecular mechanism studies showed that delay of cell cycle progression by inhibition of Aurora B kinase, regulation of metabolisms, such as suppression of glycolysis, down-regulation of angiogenesis and metastasis, and activation of intrinsic apoptosis were related to deguelin-mediated anti-tumor effect [20][21][22] . However, the effect of deguelin on EGFR signaling, as well as its inhibitory efficacy on both gefitinib sensitive and resistant cells, was not clear.…”

Phytochemical Analysis of Tephrosia vogelii across East Africa Reveals Three Chemotypes that Influence Its Use as a Pesticidal Plant

“…f. (Leguminosae) is a plant species reported to be used widely for its medicinal, insecticidal, and soil enrichment potential in tropical Africa [1][2][3][4][5][6]. Specifically, research on T. vogelii reported medicinal properties such as anti-cancer activity [7][8][9] and efficacy as an ectoparasite treatment for domestic animals including poultry [10][11][12][13][14]. A number of studies have sought to validate the reported use of T. vogelii as a botanical insecticide under laboratory and field conditions and have reported its effectiveness for crop protection and reduced impacts on beneficial ecosystem services [15][16][17].…”