Identification and Characterization of Anticancer Compounds Targeting Apoptosis and Autophagy from Chinese Native Garcinia Species

Abstract

Natural compounds from medicinal plants are important resources for drug development. Active compounds targeting apoptosis and autophagy are candidates for anti-cancer drugs. In this study, we collected Garcinia species from China and extracted them into water or ethanol fractions. Then, we performed a functional screen in search of novel apoptosis and autophagy regulators. We first characterized the anti-proliferation activity of the crude extracts on multiple cell lines. HeLa cells expressing GFP-LC3 were used to examine the effects of the crude extracts on autophagy. Their activities were confirmed by Western blots of A549 and HeLa cells. By using bioassay guided fractionation, we found that two caged prenylxanthones from Garcinia bracteata, neobractatin and isobractatin, can significantly induce apoptosis and inhibit autophagy. Our results suggest that different Garcinia species displayed various degrees of toxicity on different cancer cell lines. Furthermore, the use of a high content screening assay to screen natural products was an essential method to identify novel autophagy regulators.

Traditional Chinese medicine and cancer: History, present situation, and development

“…The rapid development of genome sequencing technology, nanoscience, and information science will help us further explore the mechanism of TCM on multiple targets, balance adjustment, and palliative effects. For example, we apply high content analysis technology to screen anti‐cancer TCM and find the basis of materials in more effective ways . The Cancer Genome Atlas will be used in research for the detection of a connection between TCM symptom patterns and genomes .…”

“…For example, we apply high content analysis technology to screen anti-cancer TCM and find the basis of materials in more effective ways. 65,66 The Cancer Genome Atlas will be used in research for the detection of a connection between TCM symptom patterns and genomes. 67,68 It can also help identify multiple target effects caused by TCM intervention, in order to predict effects and guide a timely adjustment of treatment.…”

Natural Compounds As Modulators of Non-apoptotic Cell Death in Cancer Cells

“…The cardiotonic steroid UNBS1450 0 from Calotropis procera was shown to autophagy-related cell death, by repressing NF-κB activation, as well as by downregulating c-MYC in cancer cells [231]. Oblongifolin C (OC), a natural small molecule compound extracted from Garcinia yunnanensis Hu , is a potent autophagic flux inhibitor, as described elsewhere [232-234]. Exposure to OC results in an increased number of autophagosomes and impaired degradation of SQSTM1/p62, as described in [233].…”

The natural compound neobractatin inhibits tumor metastasis by upregulating the RNA-binding-protein MBNL2

“…In recent studies, we have shown that Neobractatin (NBT), a natural compound isolated from Garcinia bracteata by C. Y. Wu ex Y. H. Li, possesses anti-tumor activities, such as inducing cell apoptosis and inhibiting autophagic flux 13 . In this study, we also found that NBT exhibited potent anti-metastatic activity against BC and LC both in vitro and in vivo.…”