Betulinic acid attenuated bleomycin-induced pulmonary fibrosis by effectively intervening Wnt/β-catenin signaling

GSH/ROS Dual-Responsive Supramolecular Nanoparticles Based on Pillar[6]arene and Betulinic Acid Prodrug for Chemo–Chemodynamic Combination Therapy

“…In summary, GSH/ROS dual-responsive novel supramolecular nanoparticles (GOx@BNPs) for chemo-chemodynamic combination therapy were developed based on water-soluble pillar [6]arene and a thioether-bridged ferrocene-modified natural anticancer BA prodrug, followed by encapsulation of GOx in the nanoparticles. The encapsulation of GOx in the nanoparticles could first catalyze the conversion of glucose into gluconic acid and H 2 O 2 , and then the generation of H 2 O 2 further reacted with ferrocene to produce highly active •OH in succession via the Fenton reaction.…”

“…Investigation of antitumor activity and mechanisms revealed that the dramatic suppression of A549 cancer cell growth induced by GOx@BNPs was derived from the elevation of ROS levels, the decrease in ATP and MTP and, finally, the induction of cell apoptosis through the synergistic interaction of CDT, starvation therapy, and chemotherapy via an intratumoral cascade reaction. This work presents a novel method to regulate the tumor microenvironment for improved CDT and the preparation of novel GSH/ROS dual-responsive supramolecular nanoparticles based on pillar [6]arene and a BA prodrug for the combination of CDT, starvation therapy, and chemotherapy, which may become a promising strategy for cancer treatment, and warrants intensive study.…”

“…Of the 175 small molecules approved for cancer treatment from the 1940s to the end of 2014, 75% are of non-synthetic origin, with 49% being either natural products or directly derived therefrom [ 5 ]. Betulinic acid (BA) is a natural lupane-type pentacyclic triterpenoid saponin usually isolated from birch tree bark, and is also present in many other botanical sources, demonstrating multiple bioactivities—particularly an antitumor effect via the elevation of ROS (reactive oxygen species) and induction of apoptosis in cancer cells [ 6 , 7 , 8 , 9 , 10 , 11 ]. However, the applications of BA are limited due to its poor water solubility, modest therapeutic effectiveness, poor bioavailability, inappropriate tissue distribution, and short plasma half-life [ 12 ].…”

“…Therefore, the tumor microenvironment (high GSH and ROS)-responsive supramolecular nanoparticles were designed and constructed via the host-guest interactions of water soluble pillar [6]arene with the ferrocene-modified anticancer product BA prodrug (BA-G). Thioether has been employed to bridge ferrocene and the natural anticancer product BA, which can be highly effectively triggered by both the high GSH and ROS in the tumor microenvironment for drug delivery [41].…”

ALCAP2 inhibits lung adenocarcinoma cell proliferation, migration and invasion via the ubiquitination of β-catenin by upregulating the E3 ligase NEDD4L

“…The Wnt/β-catenin signalling pathway plays roles in different diseases. We observed abnormal activation of the Wnt/β-catenin pathway in fibrotic disorders, similar to renal fibrosis and IPF [ 15 , 16 ], as the Wnt/β-catenin pathway can promote TGF-β-mediated fibroblast activation. Inappropriate activation of the Wnt/β-catenin pathway is also common in cancers; it can regulate the EMT, the cell cycle and tumour cell apoptosis, thus affecting the proliferation and metastasis of breast cancer, gastric cancer lung cancer, etc.…”