|
|||||
|
|
Biopharmacological considerations for accelerating drug development of deguelin,a rotenoid with potent chemotherapeutic and chemopreventive potential |
|
| Authors: | Rahel Sarah Varughese Walter Sze-Tung Lam Ahmad Abdurrahman bin Hanifah Marican S. Hema Viganeshwari Anuja Satish Bhave Nicholas L. Syn Jigang Wang PhD Andrea Li-Ann Wong MD Alan Prem Kumar PhD Peter E. Lobie PhD Soo Chin Lee MD Gautam Sethi PhD Boon Cher Goh MD Lingzhi Wang PhD |
| Affiliation: | 1. Cancer Science Institute of Singapore, National University of Singapore, Singapore Department of Pharmacology, National University Health System, Singapore;2. Cancer Science Institute of Singapore, National University of Singapore, Singapore;3. Cancer Science Institute of Singapore, National University of Singapore, Singapore Department of Haematology-Oncology, National University Health System, Singapore;4. Cancer Science Institute of Singapore, National University of Singapore, Singapore Tsinghua Berkeley Shenzhen Institute, Tsinghua University, Shenzhen, China;5. Department of Pharmacology, National University Health System, Singapore |
| 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. |
| Keywords: | chemoprevention chemotherapeutics deguelin drug development rotenoid |