Purpose: Osteosarcoma is the most common malignancy of the bone in children and adolescents. There is an urgent need for the development of novel drugs to treat it. Nudol(1), a phenanthrene compound from the traditional Chinese medicine, Dendrobium nobile, exhibited antiproliferative activity against osteosarcoma cells. Therefore, the aim of the present study was to investigate the role and underlying mechanism of nudol(1) as potential chemotherapy for osteosarcoma. Methods: Cell viability was determined by MTT assay. Cell-cycle phase distribution was analyzed by flow cytometry and Western blot. DAPI staining was used for morphology observation. Apoptosis was analysis via flow cytometry. The expression levels of mRNA and protein related to capase-mediated apoptotic pathway were detected by real-time PCR and western blotting. Migration was determined by wound healing assays. Results: Nudol(1) significantly decreased cell viability in several cancer cell lines. Moreover, nudol(1) caused cell cycle arrest at G2/M phase in U2OS cells, and it also induced cell apoptosis through the caspase-dependent pathway. In addition, treatment with nudol(1) suppressed the migration of U2OS cells. Conclusion: The present study, for the first time, demonstrated effects of nudol(1) on OS in vitro and the potential molecular mechanisms. Accordingly, nudol(1) might have the potential for further development as a lead compound against bone tumor.

The monounsaturated fatty acid 7(E)-9-keto-hexadec-7-enoic acid (1) and three structurally related analogues with different oxidation states and degrees of unsaturation (2–4) were discovered from a marine benthic cyanobacterial mat collected from Delta Shoal, Florida Keys. Their structures were elucidated using NMR spectroscopy and mass spectrometry. The structure of 1 contained an α,β-unsaturated carbonyl system, a key motif required for the activation of the Keap1/Nrf2−ARE pathway that is involved in the activation of antioxidant and phase II detoxification enzymes. Compounds 1–4 were screened in ARE-luciferase reporter gene assay using stably transfected HEK293 cells, and only 1 significantly induced Nrf2 activity at 32 and 10 µM, whereas 2–4 were inactive. As there is crosstalk between inflammation and oxidative stress, subsequent biological studies were focused on 1 to investigate its anti-inflammatory potential. Compound 1 induced Nqo1, a well-known target gene of Nrf2, and suppressed iNos transcript levels, which translated into reduced levels of nitric oxide in LPS-activated mouse macrophage RAW264.7 cells, a more relevant model for inflammation. RNA sequencing was performed to capture the effects of 1 on a global level and identified additional canonical pathways and upstream regulators involved in inflammation and immune response, particularly those related to multiple sclerosis. A targeted survey of marine cyanobacterial samples from other geographic locations, including Guam, suggested the widespread occurrence of 1. Furthermore, the previous isolation of 1 from marine diatoms and green algae implied a potentially important ecological role across marine algal eukaryotes and prokaryotes. The previous isolation from sea lettuce raises the possibility of dietary intervention to attenuate inflammation and related disease progression.