The mannose-binding protein from Agaricus bisporus inhibits the growth of MDA-MB-231 spheroids.

A mannose-binding protein from the mushroom Agaricus bisporus (Abmb) inhibits the growth of MDA-MB-231 cells, which is of an aggressive breast cancer subtype. This ability was observed in a monolayer cell (2D) culture setup, which often is unable to capture changes in cell morphology, polarity and division. That shortcoming may overestimate Abmb potency for its development as a pharmaceutical agent and its use in a therapy. Hence, Abmb's inhibition to the cell growth was performed in the 3D cell (spheroid) culture, which is more representative to the situation in vivo. The result showed that, although the presence of Abmb at ~14.7 µM already disrupted the MDA-MB-231 cell morphology in the 2D culture, its presence at ~16.5 µM only ceased the growth of the MDA-MB-231 spheroid. Further, Abmb is unique because structurally it belongs to the R-type lectin (RTL) family; most of mannose-binding protein is of the C-type lectin (CTL). As the natural ligand of Abmb is unknown thus the mechanism of action is unclear, Abmb effect on the cancer cells was assessed via observation of the altered expression of genes involved in the Wnt/ß-catenin signalling, which is one of the canonical pathways in the proliferation of cancer cells. The results suggested that Abmb did not alter the pathway upon exerting its anti-proliferative activity to the MDA-MB-231 cells.

Bioactive fraction from Lagerstroemia speciosa leaves (DLBS3733) reduces fat droplet by inhibiting adipogenesis and lipogenesis.

Background: Obesity has become a risk factor for metabolic diseases. One of the cellular characteristics of obesity is the occurrence of adipose cells hyperplasia. Lagerstroemia speciosa is a plant which has been used for the treatment of diabetes. Furthermore, some studies also indicated that L. speciosa possesses antiobesity activity. Its antiobesity activity was examined in the present study through adipogenesis, lipogenesis, and lipolysis pathways. Aim: DLBS3733, a bioactive fraction of L. speciosa, was explored for its potential benefits to alter obesity through adipogenesis and lipogenesis inhibition and lipolysis induction activity. Materials and methods: This study was performed using 3T3-L1 cells. mRNA level and protein expressions related to adipogenesis, lipogenesis, and lipolysis pathways were assayed in this study. Results: Antiadipogenic effects of DLBS3733 (15 µg/mL) were found to be mediated by a significant downregulation of mRNA level of multicomponents involved in adipogenesis which include C/EBPα (CCAAT/enhancer-binding protein alpha) and PPAR-γ (peroxisome proliferator-activated receptor gamma) by 75% and 80.1% (p<0.05), respectively. DLBS3733 was found to inhibit lipogenesis, as shown by the significant reductions of adiponectin excretion and mRNA level of fatty acid synthase, SREBP (sterol regulatory element-binding protein), and ACC-ß (Acetyl-CoA carboxylase) by 44.7%, 70.9%, and 83.1%, respectively (p<0.05). In addition, DLBS3733 was found to inhibit fat droplets accumulation in the cells in a dose-dependent manner through Oil-Red O staining. pAMPK protein was upregulated by 75% and ACC-ß was downregulated by 88% (p<0.05) which indicates the reduction of lipid synthesis. Meanwhile, DLBS3733 showed an insignificant effect on adipose triglyceride lipase, hormone-sensitive lipase, and carnitine palmitoyl-CoA transferase-1 which indicate that DLBS3733 does not induce lipolysis. Conclusion: These results demonstrate the inhibitory activity of DLBS3733 on adipogenesis and lipogenesis. DLBS3733 may provide an effective and potential benefit in the prevention of obesity.

Molecular effects of bioactive fraction of Curcuma mangga (DLBS4847) as a downregulator of 5α-reductase activity pathways in prostatic epithelial cells.

DLBS4847 is a standardized bioactive fraction of Curcuma mangga. In this study, we used prostate cancer (PC)-3 as the cell line to study the effects of DLBS4847 on prostatic cell viability, as well as related molecular changes associated with the decreased cell number. The observation revealed that DLBS4847 inhibited the growth of PC3 cells through downregulation of the 5α-reductase (5AR) pathway. At the transcription level, 5AR1 and androgen-receptor gene expressions were downregulated in a dose-dependent manner. Furthermore, 5AR-1 and dihydrotestosterone expression were also downregulated at the protein level. A microarray study was also performed to see the effects of DLBS4847 on differential gene expressions in prostate cancer 3 cells. Among others, DLBS4847 downregulated genes related to prostate growth and hypertrophy. Our results suggested that DLBS4847 could potentially become an alternative treatment for prostate disorders, such as benign prostatic hyperplasia. In this regard, DLBS4847 exerts its growth inhibition partially through downregulation of the 5AR pathway.