The Botanical Drug PBI-05204, a Supercritical CO2 Extract of Nerium Oleander, Is Synergistic With Radiotherapy in Models of Human Glioblastoma

Alessandro Colapietro; Peiying Yang; Alessandra Rossetti; Andrea Mancini; Flora Vitale; Sharmistha Chakraborty; Stefano Martellucci; Francesco Marampon; Vincenzo Mattei; Giovanni Luca Gravina; Roberto Iorio; Robert A Newman; Claudio Festuccia

doi:10.3389/fphar.2022.852941

The Botanical Drug PBI-05204, a Supercritical CO₂ Extract of Nerium Oleander, Is Synergistic With Radiotherapy in Models of Human Glioblastoma

Front Pharmacol. 2022 Mar 23:13:852941. doi: 10.3389/fphar.2022.852941. eCollection 2022.

Authors

Affiliations

¹ Laboratory of Radiobiology, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
² Department of Palliative, Rehabilitation and Integrative Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
³ Laboratory of Neurophysiology, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
⁴ Biomedicine and Advanced Technologies Rieti Center, Sabina Universitas, Rieti, Italy.
⁵ Laboratory of Experimental Medicine and Environmental Pathology, University Hub "Sabina Universitas", Rieti, Italy.
⁶ Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Rome, Italy.
⁷ Division of Radiation Oncology, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
⁸ Laboratory of Biology, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
⁹ Phoenix Biotechnology, Inc., San Antonio, TX, United States.

Abstract

Glioblastoma multiforme (GBM) is the most common as well as one of the most malignant types of brain cancer. Despite progress in development of novel therapies for the treatment of GBM, it remains largely incurable with a poor prognosis and a very low life expectancy. Recent studies have shown that oleandrin, a unique cardiac glycoside from Nerium oleander, as well as a defined extract (PBI-05204) that contains this molecule, inhibit growth of human glioblastoma, and modulate glioblastoma patient-derived stem cell-renewal properties. Here we demonstrate that PBI-05204 treatment leads to an increase in vitro in the sensitivity of GBM cells to radiation in which the main mechanisms are the transition from autophagy to apoptosis, enhanced DNA damage and reduced DNA repair after radiotherapy (RT) administration. The combination of PBI-05204 with RT was associated with reduced tumor progression evidenced by both subcutaneous as well as orthotopic implanted GBM tumors. Collectively, these results reveal that PBI-05204 enhances antitumor activity of RT in preclinical/murine models of human GBM. Given the fact that PBI-05204 has already been examined in Phase I and II clinical trials for cancer patients, its efficacy when combined with standard-of-care radiotherapy regimens in GBM should be explored.

Keywords: DNA repair; PBI-05204; apoptosis; glioblastoma; oleandrin; radiotherapy.