Apoptosis, also called programmed cell death, is morphologically characterized by cell shrinkage, membrane remodeling, cell blebbing, chromatin condensation and DNA fragmentation with apoptotic bodies.1-3) Apoptosis activation has been considered a good target in cancer therapies. 4,5) In general, apoptosis is regulated by pro-apoptotic and antiapoptotic proteins of the Bcl-2 family and executed through caspases (or cysteine-aspartic proteases), chiefly via two major and inter-related pathways, i.e., the mitochondria-dependent "intrinsic" cytochrome c/caspase-9 pathway and the death receptor-mediated "extrinsic" caspase-8 pathway. [6][7][8] Additionally, apoptosis is controlled by various cell signaling pathways such as the phosphoinositide 3-kinase (PI3K)/AKT survival pathway, regulating apoptosis chiefly by blocking caspase-9 and the mitochondria damaging Bcl-2 family protein, Bad, through phosphorylative inactivation. 9)Tanshinone IIA (Tan IIA,14,6,8,13, Fig. 1A), one of the phytochemical compounds isolated from the Chinese medicinal herb Danshen (root of Salvia miltiorrhiza BUNGE), has been reported to exert diverse biological properties including anti-oxidative, 3,10,11) anti-angiogenic, 12) and anti-inflammatory activities.13) More importantly, anti-cancer activities have been reported including human hepatoma, [14][15][16][17] breast cancer 18) and leukemia. 19) However, there is no report of anticancer activity of Tan IIA on prostate cancer cells. Thus, in the present study, we investigated the cytocidal/apoptosis effect against prostate cancer cell lines of different pathogenetic make-up: LNCaP (p53 null, phosphate and tensin homolog (PTEN) null-high AKT, androgen sensitive) and PC-3 (p53 null, PTEN null-high AKT, androgen receptor null). Our mechanistic investigations suggested an involvement of mitochondria-intrinsic caspase activation cascade and inhibition of PI3K/AKT pathway. MATERIALS AND METHODSTanshinone IIA Isolation The procedure of Tan IIA (Fig. 1A) isolation is as reported by Choi and colleagues. 20)Cell Culture Human prostate cancer cells LNCaP (ATCC CRL 1740, p53 wild type, PTEN mutant-high AKT) and PC3 (ATCC CRL 1435, p53 null, PTEN null-high AKT), and breast cancer cells MDA-MB-231 (ATCC HTB 26, p53 mutant, wild type PTEN-low AKT) were obtained from American Type Culture Collection (ATCC) and maintained in RPMI 1640 supplemented with 10% fetal bovine serum (FBS) and 2 mmol/l L-glutamine, 10 mmol/l N-(2-hydroxyethyl)piperazine-NЈ-2-ethanesulfonic acid (HEPES), 1 mmol/l sodium pyruvate, and 4.5% D-glucose without antibiotics.Cytotoxicity Assay The cytotoxicity of Tan IIA was assessed by a tetrazolium salt, 2,3-bis[2-methyloxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide (XTT) assay. LNCaP or PC3 cells were seeded onto 96-well microplates at a density of 1ϫ10 4 cells per well in 100 ml of complete medium. After incubation for 24 h, cells were exposed to var- IIA; 14,16-epoxy-20-nor-5(10),6,8,13,15-abietapentaene-11,12-dione), a phytochemical derived from the roots of Salvia miltio...

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When injecting material into the skin using a pneumatic needle-free injector, higher-pressure injections result in a hole with smaller area than lower-pressure injections. The depth and shape of skin penetration vary according to the amount of pressure applied. For materials of low density and viscosity, there is a greater difference in penetration depth according to the degree of pressure. Lasers Surg. Med. 48:624-628, 2016. © 2016 Wiley Periodicals, Inc.

Anethole is known to possess anti-inflammatory and anti-tumor activities and to be a main constituent of fennel, anise, and camphor. In the present study, we evaluated anti-metastatic and apoptotic effects of anethole on highly-metastatic HT-1080 human fibrosarcoma tumor cells. Despite weak cytotoxicity against HT-1080 cells, anethole inhibited the adhesion to Matrigel and invasion of HT-1080 cells in a dose-dependent manner. Anethole was also able to down-regulate the expression of matrix metalloproteinase (MMP)-2 and -9 and up-regulate the gene expression of tissue inhibitor of metalloproteinase (TIMP)-1. The similar inhibitory effect of anethole on MMP-2 and -9 activities was confirmed by zymography assay. Furthermore, anethole significantly decreased mRNA expression of urokinase plasminogen activator (uPA), but not uPA receptor (uPAR). In addition, anethole suppressed the phosphorylation of AKT, extracellular signal-regulated kinase (ERK), p38 and nuclear transcription factor kappa B (NF-k kB) in HT-1080 cells. Taken together, our findings indicate that anethole is a potent anti-metastatic drug that functions through inhibiting MMP-2/9 and AKT/mitogen-activated protein kinase (MAPK)/NF-k kB signal transducers.

Summary Background Numerous fillers are increasingly used for augmentation of volume loss and relaxation of facial wrinkles. Collagen stimulators are the latest next‐generation dermal fillers that can induce neocollagenesis. To investigate biophysical characteristics, safety, and efficacy of newly developed polydioxanone (PDO) filler in comparison with poly‐l lactic acid (PLLA) and polycaprolactone (PCL) fillers. Methods In vitro assay, morphology of particles, and rheological property of fillers were measured. A total of 24 female hairless mice (SKH1‐Hrhr) were randomly divided into three groups and injected with PDO, PLLA, or PCL fillers. Durability of fillers was assessed at 0, 3 days, and 1, 4, 8, 12 weeks after injection using folliscope and PRIMOS. To determine biocompatibility and neocollagenesis, histologic evaluation was performed at 1, 4, 8, and 12 weeks after injection. Efficacy was also evaluated based on skin surface roughness changes using PRIMOS in a hairless mouse photoaging model. Results In the particle morphology test, PDO microspheres had an irregular surface and were spherical and uniformly sized. PDO filler demonstrated similar neocollagenesis and inflammatory response to other collagen stimulators. PDO filler showed better biodegradability than PLLA and PCL fillers. In the hairless mouse photoaging model, there was a statistically significant decrease in skin surface roughness after PDO filler injection. Conclusions Our data suggest that newly developed collagen stimulating PDO filler might be a safe and effective option for correction of volume loss and rejuvenation of photoaging skin.