Borneol and Luteolin from Chrysanthemum morifolium Regulate Ubiquitin Signal Degradation

Abstract

Targeting the two degradation systems, ubiquitin proteasome pathway and ubiquitin signal autophagy lysosome system, plays an important function in cancer prevention. Borneol is called an "upper guiding drug". Luteolin has demonstrated anticancer activity. The fact that borneol regulates luteolin can be sufficient to serve as an alternative strategy. Borneol activates luteolin to inhibit E1 and 20S activity (IC = 118.8 ± 15.7 μM) and perturb the 26S proteasome structure in vitro. Borneol regulates luteolin to inhibit 26S activity (IC = 157 ± 19 μM), induces apoptosis (LC = 134 ± 4 μM), and causes pre-G1 and G0/G1 arrest in HepG2 cells. Borneol regulates luteolin to induce ubiquitin signal autophagic degradation, resulting in induction of E1, reduction of USP47, and accumulation of p62 in HepG2 reporter cells. Interestingly, luteolin decreased Ub conjugates, while borneol increased the accumulation of Ub conjugates in HepG2 reporter cells. E1, p62, and ubiquitin levels were downregulated in borneol-treated HepG2 reporter cells at 24 h. These observations suggest a potential autophagic inhibitor of borneol that may guide luteolin in the ubiquitin proteasome pathway and the ubiquitin signal autophagic degradation.

A Narrative Review of the Antitumor Activity of Monoterpenes from Essential Oils: An Update

“…Natural borneol (NB) has been used as a promoter of drug absorption; thus, it was seen that borneol could potentiate the cellular uptake of bisdemethoxycurcumin (possible anticancer activity) [ 36 ]. Besides that, borneol can also act as an “upper guiding drug,” because it has a potential autophagic inhibitor activity that may guide luteolin (anticancer activity) in the ubiquitin-proteasome pathway and the ubiquitin-signal autophagic degradation [ 37 ]. It was also seen that borneol increased the blood-brain barrier permeability and intracellular uptake of doxorubicin (DOX), which potentiated DOX-induced G2/M cell cycle arrest and inhibited U251 human glioma xenograft growth in vivo through combined treatment of DOX with natural borneol [ 38 ].…”

Development and Application of a Cultivar-Specific Sequence-Characterized Amplified Region (SCAR) Marker for the Detection of Chrysanthemum morifolium Ramat. ‘Daboju’

“…C. morifolium preparations are slightly cold in effect, with a sweet and bitter taste, with effects on wind, clearing heat, liver problems (ping mingmu tea), and for detoxification issues. Many studies have shown that the main active ingredients of chrysanthemum medicinal preparations include flavonoids, phenylpropanoids, and volatile oils, which have antiviral, anti-tumor, and anti-inflammatory effects [ 4 , 5 , 6 ]. Famous Chinese herbal medicine books, such as the ’Chinese Medicine Dictionary’ and ’Chinese Materia Medica,’ recorded that the ‘Boju’ type was the highest quality of medicinal chrysanthemum in China, and was mainly produced in Bozhou City, An’hui Province.…”