TY - JOUR
T1 - Natural HSP90 inhibitors as a potential therapeutic intervention in treating cancers
T2 - A comprehensive review
AU - Liew, Hui Yi
AU - Tan, Xin Yoong
AU - Chan, Hong Hao
AU - Khaw, Kooi Yeong
AU - Ong, Yong Sze
N1 - Publisher Copyright:
© 2022 Elsevier Ltd
PY - 2022/7
Y1 - 2022/7
N2 - Heat shock protein 90 (Hsp90) has evolved as a cancerous cell growth regulator by stabilising various oncogenic kinases. Upon the Hsp90 inhibition, the expression of its client proteins is downregulated and thus leads to denaturation of cellular proteins and cancer cell death. Hsp90 inhibitors, particularly those naturally derived from plants, fungi and bacteria, have gained substantial interest as a feasible therapeutic approach for cancer treatment due to their diverse pharmacological properties. In order to gain insights into the potential development of more efficacious Hsp90 inhibitors for cancer treatment, this review is conducted to analyse both in vitro and in vivo data on the chemical and biological activities of natural Hsp90 inhibitors. The systematic search was conducted in databases (PubMed, Scopus and Web of Science) with terms “Hsp90 inhibitor” and “cancer”, prompting a total of 61 articles after screening with inclusion criteria. This comprehensive review systematically summarised the efficacy of 14 different classes of naturally derived Hsp90 inhibitors in cancerous cell and animal tumour models by consolidating the primary outcomes in terms of IC50, reduction of tumour size and physicochemical properties. The detailed pharmacodynamic (the structure-activity relationship, mechanism of action) and pharmacokinetics (toxicity, oral bioavailability) of these Hsp90 inhibitors together with the study limitations were discussed. Collectively, these findings emphasise the necessity of comprehending the molecular mechanisms as well as the correlation of Hsp90 and its relative client proteins to drive the generation of viable Hsp90 inhibitors with improved pharmacodynamic and pharmacokinetic profiles.
AB - Heat shock protein 90 (Hsp90) has evolved as a cancerous cell growth regulator by stabilising various oncogenic kinases. Upon the Hsp90 inhibition, the expression of its client proteins is downregulated and thus leads to denaturation of cellular proteins and cancer cell death. Hsp90 inhibitors, particularly those naturally derived from plants, fungi and bacteria, have gained substantial interest as a feasible therapeutic approach for cancer treatment due to their diverse pharmacological properties. In order to gain insights into the potential development of more efficacious Hsp90 inhibitors for cancer treatment, this review is conducted to analyse both in vitro and in vivo data on the chemical and biological activities of natural Hsp90 inhibitors. The systematic search was conducted in databases (PubMed, Scopus and Web of Science) with terms “Hsp90 inhibitor” and “cancer”, prompting a total of 61 articles after screening with inclusion criteria. This comprehensive review systematically summarised the efficacy of 14 different classes of naturally derived Hsp90 inhibitors in cancerous cell and animal tumour models by consolidating the primary outcomes in terms of IC50, reduction of tumour size and physicochemical properties. The detailed pharmacodynamic (the structure-activity relationship, mechanism of action) and pharmacokinetics (toxicity, oral bioavailability) of these Hsp90 inhibitors together with the study limitations were discussed. Collectively, these findings emphasise the necessity of comprehending the molecular mechanisms as well as the correlation of Hsp90 and its relative client proteins to drive the generation of viable Hsp90 inhibitors with improved pharmacodynamic and pharmacokinetic profiles.
KW - Cancer
KW - Heat shock protein
KW - Hsp90
KW - Tumour
UR - http://www.scopus.com/inward/record.url?scp=85131045838&partnerID=8YFLogxK
U2 - 10.1016/j.phrs.2022.106260
DO - 10.1016/j.phrs.2022.106260
M3 - Review Article
C2 - 35577308
AN - SCOPUS:85131045838
SN - 1043-6618
VL - 181
JO - Pharmacological Research
JF - Pharmacological Research
M1 - 106260
ER -