Reduction of matrix metalloproteinase-9 expression by culture filtrate of Paecilomyces farinosus J3

Abstract

Abstract. the aim of the present study was to investigate the anti-tumor effects of a culture filtrate of Paecilomyces farinosus J3. Various anti-tumor assays using B16 melanoma cells were carried out. Paecilomyces farinosus J3 significantly decreased the wound healing capability, invasiveness and angiogenic activity, which was confirmed by wound healing, human umbilical vein endothelial cell and invasion assays. Paecilomyces farinosus J3 strongly inhibited cell migration, tube formation and the angiogenic process in a concentrationdependent manner. Zymographic analysis also indicated a reduced expression of matrix metalloproteinase-9 (mmp-9), a 92-kda gelatinase. taken together, the results indicate that the anti-tumor activities of Paecilomyces farinosus J3 originate from the reduction of mmp-9 expression in B16F10 cells. Introductioncancer is a progressive disease that affects many types of tissues, as well as organs, in the human body (1). cancer progression and metastasis is a complicated process. cells move through the blood and invade neighboring tissue by degrading the extracellular matrix (Ecm) (2). in these multiprocesses, angiogenesis plays a pivotal role in the formation of new blood vessels in the newly colonized areas, and thus in the formation of additional metastatic lesions (3,4). the Ecm includes a wide variety of proteins, which can be degraded by many matrix metalloproteinases (mmps). mmps are a family of highly conserved zinc-dependent peptidases capable of degrading the Ecm (3).anti-tumor agents have been shown to inhibit mmp-9 activity in the Ecm via the binding of the nF-κB transcription factor with the mmp-9 promoter (5). this suggests that anti-tumor agents play a role in anti-invasion and/or anti-angiogenesis, as well as in caspase-3 inhibition (6). cell motility, and in particular cell migration, affect tumor progression and metastasis (7). the signaling pathways responsible for regulating cell motility involve various nuclear transcription factors, as well as morphological changes in the cytoskeleton that modify interactions among membrane-and Ecm-bound proteins (e.g., cdc, rho and rac family proteins), which mediate cellular and membrane morphology by controlling the polymerization-depolymerization process of the actin cytoskeleton (8).Cordyceps and Paecilomyces sp. are popular entomopathogenic fungi, which have been broadly called dongchunghacho (winter worm summer grass) in Korea (8-11). Paecilomyces sp. has been investigated for industrial purposes in order to be cultivated on a large scale. however, the precise biological mechanisms of functionality and bioavailability require investigation.in this study, we show that Paecilomyces farinosus J3, which was collected and isolated from mansusan, Korea, decreases cell migration, invasion and tube formation, suggesting that this activity may have originated from the pathway of mmp-9 inhibition. Our findings, in combination with previous studies, strongly suggest that Paecilomyces farinosus J3 should be considered a good candidate for ...

Is cancer a severe delayed hypersensitivity reaction and histamine a blueprint?

“…In general, the age‐associated senescence in organ systems and initiation or progression of a wide range of chronic diseases involves minor or major adaptations or alterations in the integrity of architecture (morphology), function (behavior), biochemical, bioenergetics, immunological (cell mediated or humoral or CMI‐HI), mechanical and physical properties in tissues/cells that alter the intra‐, extra‐cellular components including declines in oxygen consumption [4–9, 36–60]. Among age‐associated biological readjustments in tissues/organs, the sustained oxidative stress (sub‐clinical, unresolved inflammation) perhaps has the most adverse cumulative influence in immune and non‐immune cells (e.g., APCs, T and B cells, epithelium, endothelium, GCs) responses that would damage cellular components (e.g., membrane, cytoplasm, chromosome, mitochondria, ER, lysosome, Golgi apparatus) and related molecules (e.g., DNA/RNA, epigenetic modifications, enzymes, proteins, cytokines, lipids) in vertebrates, invertebrates and humans [4–9, 61–80].…”

“…It is also important to note that from birth toward adulthood and aging or during induction of diseases, the multi‐cellular organ systems of the human body is subject to continuous energy‐demanding wear and tear processes in order to accommodate the Yin and Yang events and the repairing, remodeling and adaptation of tissues. Aging process itself is a dynamic phenomenon of biological regeneration and degeneration characteristic of all multi‐cellular organisms, presenting minor or major declines or skewed/retarded or accelerated biological switches [4, 6, 13–23, 33–40, 51, 54–56]. In general, the age‐induced altered natural biological and immunological activities would lead to altered effectiveness of immune surveillance, the balance between tumoricidal (Yin) vs. tumorigenic (Yang) properties of immune system, weakening the body's ability to respond to new stimuli that potentially threaten the body's survival.…”