Effects of radiotherapy and short-term starvation combination on metastatic and non-tumor cell lines

Pignatta, Sara; Cortesi, Michela; Arienti, Chiara; Zanoni, Michele; Cocchi, Claudia; Sarnelli, Anna; Arpa, D.; Piccinini, Filippo; Tesei, Anna

doi:10.1016/j.dnarep.2020.102949

Cited by 7 publications

(6 citation statements)

References 62 publications

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“…The alkaline comet assay was performed according to the manufacturer’s protocol (Comet assay, Trevigen, Gaithersburg, MD). Tail DNA was analyzed with the CometAnalyzer tool as previously described by our laboratory [ 44 ], and expressed as described by Garcia et al [ 45 ].…”

Section: Methodsmentioning

confidence: 99%

Irradiation causes senescence, ATP release, and P2X7 receptor isoform switch in glioblastoma

et al. 2022

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Glioblastoma (GBM) is the most lethal brain tumor in adults. Radiation, together with temozolomide is the standard treatment, but nevertheless, relapse occurs in nearly all cases. Understanding the mechanisms underlying radiation resistance may help to find more effective therapies. After radiation treatment, ATP is released into the tumor microenvironment where it binds and activates purinergic P2 receptors, mainly of the P2X7 subtype. Two main P2X7 splice variants, P2X7A and P2X7B, are expressed in most cell types, where they associate with distinct biochemical and functional responses. GBM cells widely differ for the level of P2X7 isoform expression and accordingly for sensitivity to stimulation with extracellular ATP (eATP). Irradiation causes a dramatic shift in P2X7 isoform expression, with the P2X7A isoform being down- and the P2X7B isoform up-modulated, as well as extensive cell death and overexpression of stemness and senescence markers. Treatment with P2X7 blockers during the post-irradiation recovery potentiated irradiation-dependent cytotoxicity, suggesting that P2X7B activation by eATP generated a trophic/growth-promoting stimulus. Altogether, these data show that P2X7A and B receptor isoform levels are inversely modulated during the post-irradiation recovery phase in GBM cells.

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Section: Methodsmentioning

confidence: 99%

Irradiation causes senescence, ATP release, and P2X7 receptor isoform switch in glioblastoma

et al. 2022

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“…The efficacy of STS combined with chemotherapy or radiotherapy in the treatment of malignant tumours has been confirmed, such as neurocytoma [ 16 ], malignant multiforme [ 24 , 25 ], breast cancer [ 26 ] and lung carcinoma [ 27 ]. A study has shown that in prostate cancer and pancreatic cancer, STS increases the radiosensitivity of metastatic tumour cells but not normal fibroblasts [ 28 ]. In several clinical studies of gynaecological malignancies, STS in combination with chemotherapy is feasible and well tolerated without significant side effects [ 29 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

Short-term starvation synergistically enhances cytotoxicity of Niraparib via Akt/mTOR signaling pathway in ovarian cancer therapy

Wang

Wan

et al. 2022

Cancer Cell Int

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Background Short-term starvation (STS) has gradually been confirmed as a treatment method that synergistically enhances the effect of chemotherapy on malignant tumours. In clinical applications, there are still some limitations of poly (ADP-ribose) polymerase inhibitors (PARPi), including understanding their effectiveness and side effects. Here, we sought to investigate the effect and mechanism of the combined use of STS and niraparib in the treatment of ovarian cancer. Methods In in vitro experiments, SKOV3 and A2780 ovarian cancer cells were treated with STS and niraparib alone or in combination. Cell viability was assessed with CCK-8, and cell cycle, apoptosis, DNA damage repair and autophagy were examined to explore the molecular mechanisms. Akt and mTOR inhibitors were used to examine any changes in DNA damage repair levels. Xenograft animal models were treated with STS and niraparib, and HE staining and immunohistochemistry were performed to examine the effects. Results The combined use of STS and niraparib inhibited cell proliferation and increased apoptosis more than niraparib application alone. In addition, compared with the niraparib group, the STS + niraparib group had increased G2/M arrest, DNA damage and autophagy, which indicated that STS pretreatment enhanced the cytotoxicity of niraparib. In animal experiments, STS did not affect the growth of transplanted tumours, but the combined treatment synergistically enhanced the cytotoxicity of niraparib. In in vivo experiments, STS did not affect the growth of transplanted tumours, but the combined treatment synergistically enhanced the cytotoxicity of niraparib and reduced the small intestinal side effects caused by niraparib chemotherapy. Conclusion STS pretreatment can synergistically enhance the cytotoxicity of niraparib. STS + niraparib is a potentially effective strategy in the maintenance therapy of ovarian cancer.

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“…Combining chemotherapy and radiotherapy with starvation can improve clinical outcomes in some types of cancer, such as melanoma 38,58–61 . Furthermore, evidence indicated that this combination could reduce chemotherapy and radiotherapy's side‐effects by selectively protecting non‐malignant cells without reducing the clinical outcome on tumor cells 62–64 . These studies have shown that short‐term starvation can increase the tumor cells' susceptibility to cell death through chemotherapy and radiotherapy, including malignancies such as metastatic melanoma, which are highly resistant to either treatment 38,58,59,62,64–66 .…”

Section: Discussionmentioning

confidence: 99%

“…38,[58][59][60][61] Furthermore, evidence indicated that this combination could reduce chemotherapy and radiotherapy's side-effects by selectively protecting non-malignant cells without reducing the clinical outcome on tumor cells. [62][63][64] These studies have shown that shortterm starvation can increase the tumor cells' susceptibility to cell death through chemotherapy and radiotherapy, including malignancies such as metastatic melanoma, which are highly resistant to either treatment. 38,58,59,62,[64][65][66] Other studies have also confirmed the combined effect of short-term starvation with chemotherapy on increasing the expression of pro-apoptotic genes in cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Cold atmospheric pressure plasma treatment combined with starvation increases autophagy and apoptosis in melanoma in vitro and in vivo

Golpour

Alimohammadi

Sohbatzadeh

et al. 2022

Experimental Dermatology

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Despite advances in therapy, malignant melanoma remains a fatal disease. Among several emerging approaches to combat cancer, cold atmospheric pressure plasma (CAP) has shown promising results as a novel antitumor agent in preclinical models so far. The technology mainly relies on the emittance of various reactive oxygen and nitrogen species (ROS/RNS) that are tumor-toxic at high concentrations. Moreover, malignant melanoma has a metabolic dimension that can be targeted by mild starvation.To this end, we investigated the combined effect of starvation and CAP treatment on melanoma in vitro and in vivo. In vitro, starvation+CAP led to cell morphology changes, decreased metabolic activity and increased lipid peroxidation accompanied by apoptosis and DNA fragmentation in murine B16 melanoma cells but not murine non-malignant L929 fibroblasts. This was paralleled by increased apoptosis (Bax, Bcl-2 and Caspase-3) and autophagy (Lc3 and Atg5)-related gene expression. In vivo, starvation reduced tumor burden. Combination with CAP treatment augmented this effect significantly, albeit there was no difference of combination treatment to CAP exposure alone. Interestingly, there was an overall greater increase of Lc3 and Atg5 in the tumor tissue compared to CAP exposure alone, while starvation-induced autophagy-related gene expression was similar to in the combination group. These data collectively suggest that CAP-derived ROS/RNS treatment and autophagy-induction augment antitumor effects in malignant melanoma in vitro and in vivo.

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Effects of radiotherapy and short-term starvation combination on metastatic and non-tumor cell lines

Cited by 7 publications

References 62 publications

Irradiation causes senescence, ATP release, and P2X7 receptor isoform switch in glioblastoma

Irradiation causes senescence, ATP release, and P2X7 receptor isoform switch in glioblastoma

Short-term starvation synergistically enhances cytotoxicity of Niraparib via Akt/mTOR signaling pathway in ovarian cancer therapy

Cold atmospheric pressure plasma treatment combined with starvation increases autophagy and apoptosis in melanoma in vitro and in vivo

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