beta-Elemonic-acid and Osteosarcoma

Osteosarcoma (OS) is a significant threat to the lives of children and young adults. Although neoadjuvant chemotherapy is the first choice of treatment for OS, it is limited by serious side-effects and cancer metastasis. β-Elemonic acid (β-EA), an active component extracted from Boswellia carterii Birdw., has been reported to exhibit potential anti-inflammatory and anticancer activities. However, the anti-tumor effects and underlying mechanisms on OS as well as pharmacokinetic characteristics of β-EA remain unknown.. This study was aimed to investigating the anti-tumor effects of β-EA on human OS, the underlying mechanisms, and the pharmacokinetic and tissue distribution characteristics.. Cell viability and colony formation assays were performed to determine the effect of β-EA cell on cell proliferation. Apoptosis rates, mitochondrial membrane potential and cell cycle features were analyzed by flow cytometry. qRT-PCR, Western blot, immunofluorescence and immunohistochemical assays were conducted to evaluate the expression levels of genes or proteins related to the pathways affected by β-EA in vitro and in vivo. Cell migration and invasion were evaluated in wound healing and Transwell chamber assays. The effects and pharmacokinetic characteristics of β-EA in vivo were evaluated by analyzing tumor suppression, pharmacokinetics and tissue distribution.. Overall, both in vitro and in vivo investigations showed the potential of β-EA for the treatment of human OS. The pharmacokinetic profile and considerable distribution in the tumor and bone tissues warrant further preclinical or even clinical studies.

Topics: Activating Transcription Factor 4; Animals; Antineoplastic Agents, Phytogenic; Apoptosis; beta Catenin; Bone Neoplasms; Cell Line, Tumor; Cell Movement; Cell Proliferation; eIF-2 Kinase; Endoplasmic Reticulum Stress; Eukaryotic Initiation Factor-2; G1 Phase Cell Cycle Checkpoints; Humans; Male; Mice, Inbred BALB C; Osteosarcoma; Phenanthrenes; Tissue Distribution; Transcription Factor CHOP; Triterpenes; Wnt Signaling Pathway; Xenograft Model Antitumor Assays