Differential Radiomodulating Action of Olea europaea L. cv. Caiazzana Leaf Extract on Human Normal and Cancer Cells: A Joint Chemical and Radiobiological Approach

Abstract

The identification of a natural compound with selectively differential radiomodulating activity would arguably represent a valuable asset in the striving quest for widening the therapeutic window in cancer radiotherapy (RT). To this end, we fully characterized the chemical profile of olive tree leaf polyphenols from the Caiazzana cultivar (OLC), autochthonous to the Campania region (Italy), by ultra-high-performance liquid chromatography–high-resolution mass spectrometry (UHPLC-HR-MS). Oleacein was the most abundant molecule in the OLC. Two normal and two cancer cells lines were X-ray-irradiated following 24-h treatment with the same concentration of the obtained crude extract and were assessed for their radioresponse in terms of micronucleus (MN) induction and, for one of the normal cell lines, of premature senescence (PS). Irradiation of pre-treated normal cells in the presence of the OLC reduced the frequency of radiation-induced MN and the onset of PS. Conversely, the genotoxic action of ionising radiation was exacerbated in cancer cells under the same experimental conditions. To our knowledge, this is the first report on the dual action of a polyphenol-rich olive leaf extract on radiation-induced damage. If further confirmed, these findings may be pre-clinically relevant and point to a substance that may potentially counteract cancer radioresistance while reducing RT-associated normal tissue toxicity.

Neuro-Nutraceutical Polyphenols: How Far Are We?

“…Other interesting compounds are oleuropein aglycone and oleocanthal from extra virgin olive oil and olive leaf [ 113 ], which are also shown to effectively counteract amyloid aggregation and toxicity [ 114 ]. In particular, the phenylethanoid oleocanthal was shown to enhance the Aβ clearance across the blood–brain barrier, decreasing amyloid load in the hippocampal parenchyma and microvessels [ 115 ].…”

Ionizing Radiation, Antioxidant Response and Oxidative Damage: Radiomodulators

“…Mechanisms involved in the radiomitigating activity include the restoration of the cellular antioxidant defence mechanisms, the prevention of excessive inflammatory responses, and/or the repair of damaged tissues [ 5 ]. Finally, radiosensitizers can increase radio-induced damage in cells or tissues, and their use is mainly focused on cancer treatment, where it is especially important to induce cytotoxicity in the cancer cells without affecting healthy tissues [ 8 , 9 , 10 ].…”

“…Overall, this Special Issue provides the readers with an understanding of the latest advancements in the bioefficacy and/or mechanisms of action of several promising radiomodulators [ 2 , 3 , 5 , 7 , 9 , 10 , 13 , 14 , 15 , 16 ], the capacity of hyperthermia to increase cancer treatment efficacy [ 17 ], a new clinical model to evaluate the radio-induced damages [ 15 , 18 ], and novel IR biomarker technologies [ 19 , 20 ].…”

“…Pacifico et al evidence that a polyphenol-rich Olea europaea L. cv. Caiazzana Leaf extract mitigates radiation-induced DNA damage in normal cell lines, whereas it exacerbates radiation damage in cancer cells [ 9 ].…”

“…As a whole, these 11 research [ 2 , 3 , 7 , 9 , 13 , 14 , 15 , 16 , 18 , 19 , 20 ] and 4 review articles [ 5 , 10 , 17 , 36 ] from leading experts bring to the field exciting discussions on different aspects, new findings, and new perspectives, thus making this Special Issue an essential read for anyone interested in the impact of radiation exposure on human health.…”