Brusatol modulates diverse cancer hallmarks and signaling pathways as a potential cancer therapeutic

Abstract

Cancer is a consequence of uncontrolled cell proliferation that is associated with cell-cycle disruption. It is a multifactorial disease that depends on the modulation of numerous oncogenic signaling pathways and targets. Although a battle against cancer has been waged for centuries, this disease remains a major cause of death worldwide. Because of the development of resistance to current anticancer drugs, substantial effort has been focused on discovering more effective agents for tumor therapy. Natural products have powerful prospects as anticancer drugs. Brusatol, a component isolated from the plant Brucea javanica, has been demonstrated to efficiently combat a wide variety of tumors. Extensive studies have indicated that brusatol exhibits anticancer effects by arresting the cell cycle; promoting apoptosis; inducing autophagy; attenuating epithelial-mesenchymal transition; inhibiting migration, invasion and angiogenesis; and increasing chemosensitivity and radiosensitivity. These effects involve various oncogenic signaling pathways, including the MAPK, NF-κB, PI3K/AKT/mTOR, JAK/STAT and Keap1/Nrf2/ARE signaling pathways. This review describes the evidence suggesting that brusatol is a promising drug candidate for cancer therapeutics.

A scientometrics and visualization analysis of oxidative stress modulator Nrf2 in cancer profiles its characteristics and reveals its association with immune response

“…Nowadays, the Keap1-Nrf2-ARE signaling pathway has been deemed a classical signaling pathway in cancer, and targeting Nrf2 has become an essential strategy in cancer therapy [ 53 ]. There are many targeted drugs designed to inhibit Nrf2, and one of their essential mechanisms is that inhibition of Nrf2 expression will lead to the accumulation of reactive oxygen radicals in cancer cells, ultimately leading to cancer cell apoptosis [ [54] , [55] , [56] ].…”

Adjuvant effects of Chinese medicinal tonics on gastric, liver, and colorectal cancers—OMICs-based contributions to understanding their mechanism of action

“…Thus, single-cell transcriptomic and proteomic data may identify mutations in small populations of cells and distinguish metastatic potential cells from HCC. A number of studies show that Chinese medicines can be used for HCC metastasis ( Guo et al, 2022 ), and most of the mechanisms have been unknown, single-cell multi-OMICs may be a useful tool to unveil the metastatic mechanisms ( Peng et al, 2018 ; Sun et al, 2021c ; Wang et al, 2022 ) of tonics including Astragalus membranaceus (Fisch.) Bge.…”

Osteoblasts and osteoclasts: an important switch of tumour cell dormancy during bone metastasis

“…It is currently difficult to determine the pros and cons between these two strategies during bone metastasis. More systematic and in-depth mechanistic studies are urgently required before this knowledge can be used for therapeutic benefit [87]. Since inhibitor of apoptosis proteins (IAPs) are overexpressed in many human malignancies, IAPs antagonists have emerged as potent anticancer drug candidates [88].…”