In Vitro and In Vivo Anti-Angiogenic Activities of Panduratin A

Targeting angiogenesis has emerged as an attractive and promising strategy in anti-cancer therapeutic development. The present study investigates the anti-angiogenic potential of Panduratin A (PA), a natural chalcone isolated from Boesenbergia rotunda by using both in vitro and in vivo assays.PA exerted selective cytotoxicity on human umbilical vein endothelial cells (HUVECs) with IC(50) value of 6.91 ± 0.85 µM when compared to human normal fibroblast and normal liver epithelial cells. Assessment of the growth kinetics by cell impedance-based Real-Time Cell Analyzer showed that PA induced both cytotoxic and cytostatic effects on HUVECs, depending on the concentration used. Results also showed that PA suppressed VEGF-induced survival and proliferation of HUVECs. Furthermore, endothelial cell migration, invasion, and morphogenesis or tube formation demonstrated significant time- and dose-dependent inhibition by PA. PA also suppressed matrix metalloproteinase-2 (MMP-2) secretion and attenuated its activation to intermediate and active MMP-2. In addition, PA suppressed F-actin stress fiber formation to prevent migration of the endothelial cells. More importantly, anti-angiogenic potential of PA was also evidenced in two in vivo models. PA inhibited neo-vessels formation in murine Matrigel plugs, and angiogenesis in zebrafish embryos.Taken together, our study demonstrated the distinctive anti-angiogenic properties of PA, both in vitro and in vivo. This report thus reveals another biological activity of PA in addition to its reported anti-inflammatory and anti-cancer activities, suggestive of PA's potential for development as an anti-angiogenic agent for cancer therapy

Identification of Novel Pro-Migratory, Cancer-Associated Genes Using Quantitative, Microscopy-Based Screening

Background: Cell migration is a highly complex process, regulated by multiple genes, signaling pathways and external stimuli. To discover genes or pharmacological agents that can modulate the migratory activity of cells, screening strategies that enable the monitoring of diverse migratory parameters in a large number of samples are necessary. Methodology: In the present study, we describe the development of a quantitative, high-throughput cell migration assay, based on a modified phagokinetic tracks (PKT) procedure, and apply it for identifying novel pro-migratory genes in a cancer-related gene library. In brief, cells are seeded on fibronectin-coated 96-well plates, covered with a monolayer of carboxylated latex beads. Motile cells clear the beads, located along their migratory paths, forming tracks that are visualized using an automated, transmitted-light screening microscope. The tracks are then segmented and characterized by multi-parametric, morphometric analysis, resolving a variety of morphological and kinetic features. Conclusions: In this screen we identified 4 novel genes derived from breast carcinoma related cDNA library, whose over-expression induces major alteration in the migration of the stationary MCF7 cells. This approach can serve for high throughput screening for novel ways to modulate cellular migration in pathological states such as tumor metastasis and invasion

Microanatomy and histology of bone pathologies of extant and extinct phocid seals

This study investigates three presumed fractured phocid seal bones: An isolated metapodial and an ulna belonging to different individuals of the extinct phocid, Homiphoca capensis, from Langebaanweg and a mandible of a juvenile elephant seal (Mirounga leonina), which was included to assess the validity of the assumption that changes to bones caused by fractures are consistent across extant and extinct members of the same groups. The bones were studied using a multi-method approach, including gross morphology, microcomputed tomography (micro-CT) and histology. Micro-CT showed that the metapodial was not fractured and information drawn from other analyses suggested that the pathology was an osteosarcoma. Histology of normal and fractured regions of the mandible and ulna permitted an estimate about the fracture healing stage, and showed the bone tissue at the fracture sites to be histologically similar. A birth line found on the lateral surface of the elephant seal mandible emphasised its young age and marked the first example of a birth line in a bone of a semi-aquatic mammal. A large scope of information was obtained using this multi-method approach, which could permit insight into the life events and lifestyles of modern and extinct individuals, such as H. capensis.NRF-DST Centre of Excellence in Palaeosciences to Megan Rose Woolley, NRF African Origins Programme (AOP) Grant awarded to Prof A Chinsamy-Turan (Grant No. 117716) NRF African Origins Programme (AOP) Grant awarded to Dr R Govender (Grant No. 98834).https://www.tandfonline.com/loi/ghbi202020-11-12hj2020Mammal Research InstituteZoology and Entomolog