Exploration of anti­osteosarcoma activity of asiatic acid based on network pharmacology and in vitro experiments.

Osteosarcomas are malignant bone tumors that typically originate in the epiphyses of the long bones of the extremities in adolescents. Asiatic acid has been reported to possess anti­inflammatory, neuroprotective, antidiabetic, antitumor and antimicrobial activities. The present study used a combination of network pharmacological prediction and in vitro experimental validation to explore the potential pharmacological mechanism of asiatic acid against osteosarcoma. A total of 78 potential asiatic acid targets in osteosarcoma were identified using databases. Kyoto Encyclopedia of Genes and Genomes analysis indicated that the PI3K/AKT and MAPK signaling pathways are essential in the treatment of osteosarcoma with asiatic acid. Molecular docking revealed binding of asiatic acid to EGFR, Caspase­3, ESR1, HSP90AA1, IL­6 and SRC proteins. asiatic acid inhibited proliferation through G2/M cell cycle arrest in osteosarcoma cells. In addition, asiatic acid induced mitochondria­dependent apoptosis as demonstrated by increases in Bax and VDAC1 expression, and a decrease in Bcl­2 protein expression. The increased autophagosomes, increased LC3­II/I ratios and decreased p62 expression in the treatment group indicated that asiatic acid triggered autophagy. In addition, asiatic acid decreased the levels of phosphorylated (p­)PI3K/PI3K and p­AKT/AKT, increased reactive oxygen species (ROS) and upregulated the levels of p­ERK1/2/ERK1/2, p­p38/p38 and p­JNK/JNK in osteosarcoma cells. These results demonstrated that asiatic acid inhibited osteosarcoma cells proliferation by inhibiting PI3K/AKT and activating ROS/MAPK signaling pathways, suggesting asiatic acid is a potential agent against osteosarcoma.

Baicalin induces apoptosis and autophagy in human osteosarcoma cells by increasing ROS to inhibit PI3K/Akt/mTOR, ERK1/2 and ß-catenin signaling pathways.

Baicalin, a flavonoid derivative, exerts antitumor activity in a variety of neoplasms. However, whether baicalin exerts antitumor effects on osteosarcoma cells remains to be elucidated. In this study, treatment with baicalin reduced the proliferation and invasive potential of osteosarcoma cells and reduced the mitochondrial membrane potential, which eventually caused mitochondrial apoptosis. In addition, baicalin increased intercellular Ca2+ and ROS concentrations. Baicalin-induced apoptosis was confirmed by enhanced Bax, cleaved caspase-3, and cleaved PARP levels and decreased Bcl-2 levels. The increase in LC3-II and p62 suggested that baicalin induced autophagosome formation but ultimately inhibited downstream autophagy. Moreover, apoptosis induced by baicalin was attenuated by the addition of 3-MA. Furthermore, we found that baicalin inhibited the PI3K/Akt/mTOR, ERK1/2 and ß-catenin signaling pathways. Chelation of free Ca2+ by BAPTA-AM also inhibited both apoptosis induction and ROS concentration changes. Finally, NAC pretreatment reversed baicalin treatment outcomes, including the increase in Ca2+ concentration, induction of apoptosis and autophagy, and inhibition of the pathways. Molecular docking results indicated that baicalin might interact with the structural domain of PI3Kγ. Thus, baicalin may be considered a potential candidate for osteosarcoma treatment.

α-Carotene: a valuable carotenoid in biological and medical research.

α-Carotene, one of the C40 carotenes, is a natural lipid-soluble terpene. The chemical structure of α-carotene is based on the unsaturated polyene chain skeleton, with an ε-ring and a ß-ring on each side of the skeleton. α-Carotene is widely found in dietary fruits and vegetables, and the concentration depends on the plant species. In addition, processing methods and storage conditions used in the food and medical industries can alter the concentration of α-carotene in raw materials. This review of α-carotene summarizes the major studies on chemical structure, source, extraction, detection, biosynthesis, processing effect, bioactivity, medicine, and biotechnology. Whether α-carotene supplementation or a diet rich in fruits and vegetables has a positive effect on the prevention of cancer, cardiovascular disease, and other diseases is the focus of this study. © 2022 Society of Chemical Industry.