Nigrospora Sphaerica Products from the Flowering Dogwood Exhibit Antitumorigenic Effects Via the Translational Regulator, Ps6 Ribosomal Protein

Asha Maheshwari^1,2, Margaret Mmbaga¹ & Quincy Quick, A.^2*

¹Department of Agricultural and Environmental Sciences, Tennessee State University, Nashville, TN, USA
²Department of Biological Sciences, Tennessee State University, Nashville, TN, USA

Quincy Quick, A., Department of Biological Sciences, Tennessee State University, 3500 John A. Merritt Blvd, Nashville, TN, 37209 USA.

Keywords: Natural Product; Fungi; Secondary Metabolite; Intracellular Signaling; Cancer

Abstract

The utility of diverse species of endophytic fungi as a viable source for drug agents with clinical applicability for the treatment of human diseases continues to expand. In this study we examined secondary metabolites of Nigrospora sphaerica isolated from the flowering dogwood, Cornus florida L., for their anticancer properties on lung cancer and glioblastoma.  Molecular identification of N. sphaerica was determined using ITS-rDNA sequence.  The expression of translational pathway proteins was examined after exposure to various crude extract concentrations (2µg/ml, 4µg/ml, 8µg/ml) using immunoblotting procedures, while tumor cell migration analysis was performed using boyden chamber assays.  Crude N. sphaerica extracts exhibited antiproliferative and antimigratory effects on solid tumors as determined by cell proliferation and cell migration assays, respectively.  The antitumorigenic effects of N. sphaerica were as a consequence of negatively regulating the PI3K/Akt/mTOR translational control signaling pathway, a canonical mechanistic axis that contributes to the maintenance and progression of several human cancers.  To our knowledge this is the first evidence that demonstrates N. sphaerica from C. florida inhibits tumor cell migration, and thus disease recurrence a major factor in the therapeutic resistance of cancers to chemotherapeutic agents.

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