Mohamad R. Sarmidi

Biotechnology for Wellness Industry: Concepts and Biofactories

One of the major issues in the 21st. century facing humankind is on how to stay healthy and delay the onset of chronic metabolic diseases. Chronic metabolic chronic diseases still afflict a substantial percentage of modern human population despite the advances in medical and health care technologies. They create a long-term financial burden to the nation as well as reducing the productivity and the quality of life. In the recent years, the wellness approach to healthy living by mean of health enhancement and disease prevention has been increasing in popularity. There is a tremendous global and local interest for wellness products. Wellness sector focuses on providing products and services to a wider community to improve appearance, slow down the effect of ageing and to reduce the risk of developing chronic metabolic diseases. The wellness products are intended for the promotion of health in soil, plants, animals and human. Soil health is the foundation of wellness as healthy and productive soil produce healthy plants and crops in turn produced healthy animals for human nutrition. It is a fact that human health is closely associated with the practice of healthy life style that include consuming wholesome nutrients, living in a non-toxic environment and enhancing physical and mental fitness. These factors in turn promote the attainment and maintenance of cellular homeostasis. Under cellular homeostasis the cellular metabolic activities are at their optimum. In this regard traditional and modern biotechnology offer comprehensive list of natural ingredients and metabolites essential for cellular metabolism. These natural ingredients and metabolites are derived from microbial, algal, plant, animals, and human sources. Most of these natural products are increasingly made available by using innovative bioprocess technologies as more of them are main components of functional foods, nutraceuticals, cosmeceuticals and therapeutics. Bioprocess industries are considered as source for both health and wealth. The new concept of bioprocess industries is based on using different types of cells as small micro-bio-factories. These small biofactories belong to different classes of living organisms ranging from the most primitive prokaryotic bacterial cells up to high eukaryotic human cells. In the present review, the concept of bioprocess design and cultivation of cells up to the industrial level will be presented.

In Vitro Pro-apoptotic and Anti-migratory Effects of Ficus deltoidea L. Plant Extracts on the Human Prostate Cancer Cell Lines PC3

This study aims to evaluate the in vitro cytotoxic and anti-migratory effects of Ficus deltoidea L. on prostate cancer cells, identify the active compound/s and characterize their mechanism of actions. Two farmed varieties were studied, var. angustifolia (FD1) and var. deltoidea (FD2). Their crude methanolic extracts were partitioned into n-hexane (FD1h, FD2h) chloroform (FD1c, FD2c) and aqueous extracts (FD1a, FD2a). Antiproliferative fractions (IC50 < 30 μg/mL, SRB staining of PC3 cells) were further fractionated. Active compound/s were dereplicated using spectroscopic methods. In vitro mechanistic studies on PC3 and/or LNCaP cells included: annexin V-FITC staining, MMP depolarization measurements, activity of caspases 3 and 7, nuclear DNA fragmentation and cell cycle analysis, modulation of Bax, Bcl-2, Smac/Diablo, and Alox-5 mRNA gene expression by RT-PCR. Effects of cytotoxic fractions on 2D migration and 3D invasion were tested by exclusion assays and modified Boyden chamber, respectively. Their mechanisms of action on these tests were further studied by measuring the expression VEGF-A, CXCR4, and CXCL12 in PC3 cells by RT-PCR. FD1c and FD2c extracts induced cell death (P < 0.05) via apoptosis as evidenced by nuclear DNA fragmentation. This was accompanied by an increase in MMP depolarization (P < 0.05), activation of caspases 3 and 7 (P < 0.05) in both PC3 and LNCaP cell lines. All active plant extracts up-regulated Bax and Smac/DIABLO, down-regulated Bcl-2 (P < 0.05). Both FD1c and FD2c were not cytotoxic against normal human fibroblast cells (HDFa) at the tested concentrations. Both plant extracts inhibited both migration and invasion of PC3 cells (P < 0.05). These effects were accompanied by down-regulation of both VEGF-A and CXCL-12 gene expressions (P < 0.001). LC–MS dereplication using taxonomy filters and molecular networking databases identified isovitexin in FD1c; and oleanolic acid, moretenol, betulin, lupenone, and lupeol in FD2c. In conclusion, FD1c and FD2c were able to overcome three main hallmarks of cancer in PC3 cells: (1) apoptosis by activating of the intrinsic pathway, (2) inhibition of both migration and invasion by modulating the CXCL12-CXCR4 axis, and (3) inhibiting angiogenesis by modulating VEGF-A expression. Moreover, isovitexin is here reported for the first time as an antiproliferative principle (IC50 = 43 μg/mL, SRB staining of PC3 cells).