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Cellular and molecular effects of protons: Apoptosis induction and potential implications for cancer therapy

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Abstract

Due to their ballistic precision, apoptosis induction by protons could be a strategy to specifically eliminate neoplastic cells. To characterize the cellular and molecular effects of these hadrons, we performed dose-response and time-course experiments by exposing different cell lines (PC3, Ca301D, MCF7) to increasing doses of protons and examining them with FACS, RT-PCR, and electron spin resonance (ESR). Irradiation with a dose of 10 Gy of a 26,7 Mev proton beam altered cell structures such as membranes, caused DNA double strand breaks, and significantly increased intracellular levels of hydroxyl ions, are active oxygen species (ROS). This modified the transcriptome of irradiated cells, activated the mitochondrial (intrinsic) pathway of apoptosis, and resulted in cycle arrest at the G2/M boundary. The number of necrotic cells within the irradiated cell population did not significantly increase with respect to the controls. The effects of irradiation with 20 Gy were qualitatively as well as quantitatively similar, but exposure to 40 Gy caused massive necrosis. Similar experiments with photons demonstrated that they induce apoptosis in a significantly lower number of cells and in a temporally delayed manner. These data advance our knowledge on the cellular and molecular effects of proton irradiation and could be useful for improving current hadrontherapy protocols.

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Author notes

  1. F. Purrello

    Present address: Unità Operativa di Medicina Interna, Ospedale Cannizzaro, Catania, 95125, Italy

Authors and Affiliations

  1. Dipartimento di Scienze Biomediche, Sezione di Biologia, Genetica e Bioinformatica, Università di Catania, Catania, 95123, Italy

    C. Di Pietro, M. Ragusa, V. Di Pietro, V. Zimmitti, F. Cuda, A. Pulvirenti, R. Giugno, A. Ferro & M. Purrello

  2. Dipartimento di Medicina Interna e Medicina Specialistica, Sezione di Endocrinologia, Università di Catania, Ospedale Garibaldi, Catania, 95124, Italy

    S. Piro, M. Anello & F. Purrello

  3. Istituto di Biostrutture e Bioimmagini, CNR, Catania, 95125, Italy

    G. Tabbì

  4. Dipartimento di Scienze Biomediche, Sezione di Ematologia, Università di Catania, Catania, 95124, Italy

    U. Consoli

  5. Dipartimento di Medicina Interna e Medicina Specialistica, Sezione di Malattie Respiratorie, Università di Catania, Catania, 95125, Italy

    E. T. Salinaro, M. Caruso, C. Vancheri & N. Crimi

  6. Istituto Nazionale di Fisica Nucleare, Laboratorio Nazionale del Sud, Catania, 95125, Italy

    M. G. Sabini, G. A. P. Cirrone, L. Raffaele & G. Cuttone

  7. Dipartimento di Diagnostica per Immagini e Radioterapia, Università di Catania, Catania, 95125, Italy

    G. Privitera

  8. Dipartimento di Matematica ed Informatica, Università di Catania, Catania, 95125, Italy

    A. Pulvirenti & R. Giugno

  9. Dipartimento di Fisica e di Astronomia, Università di Catania, Catania, 95125, Italy

    S. Lo Nigro

  10. Dipartimento di Scienze Chimiche, Università di Catania, Catania, 95125, Italy

    R. Purrello

  11. Dipartimento di Scienze Biomediche, Sezione di Biologia, Genetica e Bioinformatica, Università di Catania, Catania, 95123, Italy

    M. Purrello

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  1. C. Di Pietro
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Correspondence to M. Purrello.

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Di Pietro, C., Piro, S., Tabbì, G. et al. Cellular and molecular effects of protons: Apoptosis induction and potential implications for cancer therapy. Apoptosis 11, 57–66 (2006). https://doi.org/10.1007/s10495-005-3346-1

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