Proteomic Analysis of Anticancer TCMs Targeted at Mitochondria

Abstract

Traditional Chinese medicine (TCM) is a rich resource of anticancer drugs. Increasing bioactive natural compounds extracted from TCMs are known to exert significant antitumor effects, but the action mechanisms of TCMs are far from clear. Proteomics, a powerful platform to comprehensively profile drug-regulated proteins, has been widely applied to the mechanistic investigation of TCMs and the identification of drug targets. In this paper, we discuss several bioactive TCM products including terpenoids, flavonoids, and glycosides that were extensively investigated by proteomics to illustrate their antitumor mechanisms in various cancers. Interestingly, many of these natural compounds isolated from TCMs mostly exert their tumor-suppressing functions by specifically targeting mitochondria in cancer cells. These TCM components induce the loss of mitochondrial membrane potential, the release of cytochrome c, and the accumulation of ROS, initiating apoptosis cascade signaling. Proteomics provides systematic views that help to understand the molecular mechanisms of the TCM in tumor cells; it bears the inherent limitations in uncovering the drug-protein interactions, however. Subcellular fractionation may be coupled with proteomics to capture and identify target proteins in mitochondria-enriched lysates. Furthermore, translating mRNA analysis, a new technology profiling the drug-regulated genes in translatome level, may be integrated into the systematic investigation, revealing global information valuable for understanding the action mechanism of TCMs.

Isodeoxyelephantopin induces protective autophagy in lung cancer cells via Nrf2-p62-keap1 feedback loop

“…Increasing evidences proved that natural products may be potential therapeutic agents for cancer treatment 48 , 49 , 50 and some of the them, for example, paclitaxel, vinca alkaloids and resveratrol, have been used for chemotherapy in clinic for decades. 4 , 6 , 51 ESI was previously reported to have anticancer effects by arresting G2/M phase transition, inducing ROS-dependent DNA damage and mitochondrial-mediated apoptosis, 10 and suppressing the activity of nuclear factor- κ B.…”

CD38 enhances the proliferation and inhibits the apoptosis of cervical cancer cells by affecting the mitochondria functions

“…Mitochondrion is an important regulator in cellular energy homeostasis and plays a major role in regulating cell apoptotic process . Many researchers have elucidated that bioactive compounds can stimulate mitochondria to trigger cell apoptosis . With increased apoptosis, the mitochondrial membrane potential decreased.…”

“…41 Many researchers have elucidated that bioactive compounds can stimulate mitochondria to trigger cell apoptosis. 42 With increased apoptosis, the mitochondrial membrane potential decreased. Thus, the loss of mitochondrial transmembrane potential indicates cell apoptosis.…”

Buyang Huanwu Decoction attenuates H2O2-induced apoptosis by inhibiting reactive oxygen species-mediated mitochondrial dysfunction pathway in human umbilical vein endothelial cells

“…Mitochondria are key regulators of cellular energy homeostasis and play a central role in apoptosis [ 39 ]. Mitochondrial apoptotic signals decrease the MMP, causing Cyt-c and Smac and other contents to leak from the mitochondria [ 4 , 5 ]. Smac speeds up apoptosis and Cyt-c promotes apoptosis by activating caspase-3 [ 4 , 6 ].…”