Page 436 - Read Online

J Cancer Metastasis Treat 2019;5:31 I http://dx.doi.org/10.20517/2394-4722.2019.21 Page 24 of 36

30. The effects of water extract of Ruta graveolens on glioblastoma and melanoma cells is
selective and depends on REST/NRSF expression

1
1
3
2
1
Luca Colucci D’Amato , Maria Teresa Gentile , Olga Pastorino , Adriana Bajetto , Asa Fex-Svenningsen ,
Tullio Florio 2
1 Laboratory of Molecular and Cellular NeuroPathology, Di.S.T.A.Bi.F., University of Campania “L. Vanvitelli”,
Caserta 81100, Italy.
2 Sezione di Farmacologia, Dipartimento di Medicina Interna & Centro di Eccellenza per la Ricerca Biomedica
(CEBR), Università di Genova, Genova 16132, Italy.
3 Department of Neurobiology Research, University of Southern Denmark, Odense DK-5000, Denmark.

Heterogeneity and recurrent relapse of tumors, drugs resistance and the lack of selectivity of current
chemotherapy calls for new drugs.

Here we report that RGWE is able to kill a number of glioblastoma (GBM) cell lines and cancer stem cells as
shown by MTT and trypan blue assay. In particularly, we analyzed U87MG, U138, C6 cell lines as well as 3
cancer stem cells originated from patients affected by GBM. RGWE, differently to temozolomide and cisplatin,
does not show any toxic activity towards differentiated neurons. Interestingly, differently to GBM cells
responsive to RGWE, T98G GBM cell line, unresponsive to RGWE, do not express the transcription factor
REST/NRSF, encoding a zinc finger protein that function as a master regulator of neural cell differentiation
in normal physiological conditions. NRSF is highly expressed in embryonic stem cells but reduced rapidly
in neuron progenitors and maintained at very low levels after differentiation. In contrast, in neuroepithelial
tumors, high levels of NRSF are expressed in medulloblastomas, neuroblastomas and multiform glioblastoma
and are correlated with the proliferation and severity of these tumors. We observed that down regulation of
REST/NRSF in U87MG and C6 cells by means of siRNA, prevents RGWE cytotoxic effects.

We also found that human melanoma cell lines, HNCB and A375 expressing high and low levels of REST/
high
NRSF respectively, respond differently to RGWE. HNCB (REST ) cells die upon RGWE administration
whereas A375 (REST ) cells are unresponsive. RGWE stimulation is able to affect also cell migration as
low
shown by wound assay. Upon siRNA-mediated REST down-regulation, HNCB cells show unresponsiveness
to RGWE’s effects.

Finally, we evaluated the effects of RGWE in the tube formation assay on Matrigel, an angiogenic assay. We
found that RGWE is able to impair tubule network formation when administered to human endothelial
cells, HUVEC.

31. A natural agent bitter melon exerts strong efficacy against pancreatic cancer in combination
with gemcitabine in patient derived xenografts

Rajesh Agarwal

Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and
Pharmaceutical Sciences, Colorado 80045, USA.

Pancreatic cancer (PanC) remains the 4th leading cause of cancer related-deaths in U.S. resulting in a
dismal survival rate of < 5%. This generates a critical need for identifying novel non-toxic agents aimed at