Oncoscience

Human recombinant RNASET2: A potential anti-cancer drug

Levava Roiz1, Patricia Smirnoff1, Iris Lewin1, Oded Shoseyov2, Betty Schwartz3

1T2 BIOTECH Ltd, Weizmann Science Park, Ness Ziona, ISRAEL

2The Robert H. Smith Institute of Plant Science and Genetics in Agriculture and School of Nutritional Sciences Institute of Biochemistry, Food Science and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, ISRAEL

3School of Nutritional Sciences Institute of Biochemistry, Food Science and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, ISRAEL

Correspondence to:

Betty Schwartz, email: betty.schwartz@mail.huji.ac.il

Oded Shoseyov, email: oded.shoseyov@mail.huji.ac.il

Keywords: actin-binding, tumorigenesis, angiogenesis, ribonuclease

Received: January 27, 2016     Accepted: February 23, 2016     Published: March 04, 2016

ABSTRACT

The roles of cell motility and angiogenetic processes in metastatic spread and tumor aggressiveness are well established and must be simultaneously targeted to maximize antitumor drug potency. This work evaluated the antitumorigenic capacities of human recombinant RNASET2 (hrRNASET2), a homologue of the Aspergillus niger T2RNase ACTIBIND, which has been shown to display both antitumorigenic and antiangiogenic activities. hrRNASET2 disrupted intracellular actin filament and actin-rich extracellular extrusion organization in both CT29 colon cancer and A375SM melanoma cells and induced a significant dose-dependent inhibition of A375SM cell migration. hrRNASET2 also induced full arrest of angiogenin-induced tube formation and brought to a three-fold lower relative HT29 colorectal and A375SM melanoma tumor volume, when compared to Avastin-treated animals. In parallel, mean blood vessel counts were 36.9% lower in hrRNASET2-vs. Avastin-treated mice and survival rates of hrRNASET2-treated mice were 50% at 73 days post-treatment, while the median survival time for untreated animals was 22 days. Moreover, a 60-day hrRNASET2 treatment period reduced mean A375SM lung metastasis foci counts by three-fold when compared to untreated animals. Taken together, the combined antiangiogenic and antitumorigenic capacities of hrRNASET2, seemingly arising from its direct interaction with intercellular and extracellular matrices, render it an attractive anticancer therapy candidate.


PII: 295