Human recombinant RNASET2: A potential anti-cancer drug
Levava Roiz1, Patricia Smirnoff1, Iris Lewin1
1T2 BIOTECH Ltd, Weizmann Science Park, Ness Ziona, ISRAEL.
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.
Insights
Human recombinant RNASET2 (hrRNASET2) effectively targets cancer cell motility and angiogenesis. This dual action significantly reduces tumor growth and metastasis, showing promise as an anticancer therapy.
Area of Science:
- Oncology
- Biochemistry
- Molecular Biology
Background:
- Cell motility and angiogenesis are critical drivers of tumor metastasis and aggressiveness.
- Targeting these processes simultaneously is key to enhancing antitumor drug efficacy.
- Human recombinant RNASET2 (hrRNASET2) exhibits known antitumorigenic and antiangiogenic properties.
Purpose of the Study:
- To evaluate the antitumorigenic and antiangiogenic capacities of hrRNASET2.
- To assess hrRNASET2's impact on cancer cell structure, migration, and tumor progression.
- To compare hrRNASET2's efficacy against established treatments like Avastin.
Main Methods:
- Investigated hrRNASET2's effects on actin filament organization in colon cancer (HT29) and melanoma (A375SM) cells.
- Assessed hrRNASET2's inhibition of cancer cell migration and angiogenin-induced tube formation.
- Quantified tumor volume, blood vessel density, metastasis foci, and survival rates in animal models.
Main Results:
- hrRNASET2 disrupted actin organization and inhibited A375SM cell migration.
- hrRNASET2 induced complete arrest of angiogenin-induced tube formation.
- hrRNASET2 treatment resulted in significantly lower tumor volumes, reduced blood vessel counts, and decreased lung metastasis compared to controls and Avastin.
- hrRNASET2 treatment improved survival rates in treated mice.
Conclusions:
- hrRNASET2 possesses combined antiangiogenic and antitumorigenic capacities.
- These effects appear to stem from hrRNASET2's interaction with intercellular and extracellular matrices.
- hrRNASET2 is a promising candidate for novel anticancer therapy.
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