Mitotic Catastrophe Induced in HeLa Tumor Cells by Photodynamic Therapy with Methyl-aminolevulinate

Mascaraque, Marta; Delgado-Wicke, Pablo; Damián, Alejandra; Lucena, Silvia Rocío; Carrasco, Elisa; Juarranz, Ángeles

doi:10.3390/ijms20051229

Cited by 13 publications

(9 citation statements)

References 56 publications

(89 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cell cycle arrest in the S/G2/M phase and induction of mitotic catastrophe in lung tumor cells have also been reported after treatment with ophiopogonin B [30] and in HeLa cells after the treatment with methyl-amino levulinate, a photosensitizer used in photodynamic therapy [31]. We observed that MOLT-4 cells transfected with either normal or mutated Ras were arrested in the S phase of the cell cycle.…”

Section: Discussionsupporting

confidence: 71%

Abnormal expression ofH-Rasinduces S-phase arrest and mitotic catastrophe in human T-lymphocyte leukemia

et al. 2023

View full text Add to dashboard Cite

Background: Leukemia is a neoplasm with high incidence and mortality rates. Mitotic death has been observed in tumor cells treated with chemotherapeutic agents. Ras family proteins participate in the transduction of signals involved in different processes, such as proliferation, differentiation, survival, and, paradoxically, initiation of cell death. Methods:This study investigated the effect of H-Ras expression on human T-cell acute lymphoblastic leukemia MOLT-4 cells. Cells were electroporated with either wild-type (Ras wt ) or oncogenic mutant in codon 12 exon 1 (Ras mut ) versions of H-Ras gene and stained for morphological analysis. Cell viability was assessed using trypan blue staining and cell cycle analysis using flow cytometry. H-Ras gene expression was determined using quantitative real-time reverse transcription polymerase chain reaction.The t, ANOVA, and Scheffe tests were used for statistical analysis.Results: Human T-cell acute lymphoblastic leukemia MOLT-4 cells showed nuclear fragmentation and presence of multiple nuclei and micronuclei after transfection with either wt or mutant H-Ras genes.Cell cycle analysis revealed a statistically significant increase in cells in the S phase when transfected with either wt (83.67%, P<0.0005) or mutated (81.79%, P<0.0001) H-Ras genes. Although similar effects for both versions of H-Ras were found, cells transfected with the mutated version died at 120 h of mitotic catastrophe. Conclusion: Transfection of human T-cell acute lymphoblastic leukemia MOLT-4 cells with eithernormal or mutated H-Ras genes induced alterations in morphology, arrest in the S phase, and death by mitotic catastrophe.

show abstract

Section: Discussionsupporting

confidence: 71%

Abnormal expression ofH-Rasinduces S-phase arrest and mitotic catastrophe in human T-lymphocyte leukemia

et al. 2023

View full text Add to dashboard Cite

show abstract

“…The effect of RDT appears to be strong in mitochondria since PpIX is synthesized in the mitochondrial intermembrane space. Even though MMP was examined in this study, it is necessary to further investigate the effect on mitochondrial function and morphology [28,29].…”

Section: Discussionmentioning

confidence: 99%

Verification of 5-Aminolevurinic Radiodynamic Therapy Using a Murine Melanoma Brain Metastasis Model

Takahashi

Nagasawa

Ikemoto

et al. 2019

IJMS

View full text Add to dashboard Cite

Melanoma is a highly aggressive cancer with a propensity for brain metastases. These can be treated by radiotherapy, but the radiation-resistant nature of melanoma makes the prognosis for melanoma patients with brain metastases poor. Previously, we demonstrated that treatment of mice with subcutaneous melanoma with 5-aminolevurinic acid (5-ALA) and X-rays in combination, (“radiodynamic therapy (RDT)”), instead of with 5-ALA and laser beams (“photodynamic therapy”), improved tumor suppression in vivo. Here, using the B16-Luc melanoma brain metastasis model, we demonstrate that 5-ALA RDT effectively treats brain metastasis. We also studied how 5-ALA RDT damages cells in vitro using a B16 melanoma culture. Cell culture preincubated with 5-ALA alone increased intracellular photosensitizer protoporphyrin IX. On X-ray irradiation, the cells enhanced their ∙OH radical generation, which subsequently induced γH2AX, a marker of DNA double-strand breaks in their nuclei, but decreased mitochondrial membrane potential. After two days, the cell cycle was arrested. When 5-ALA RDT was applied to the brain melanoma metastasis model in vivo, suppression of tumor growth was indicated. Therapeutic efficacy in melanoma treatment has recently been improved by molecular targeted drugs and immune checkpoint inhibitors. Treatment with these drugs is now expected to be combined with 5-ALA RDT to further improve therapeutic efficacy.

show abstract

“…Both effects vanished over time and the remaining cells that survived proliferated again. In this sense, induction of cell cycle blockage at metaphase-anaphase transition with multipolar spindles has also been described in HeLa cells by PDT with Methyl-aminolevulinate (a PpIX precursor intermediate of heme synthesis), which trigger cell death by apoptosis [ 51 ]. In contrast, CPT11 lip treatments showed longer-term effects, including polyploidization and the onset of senescence morphologies, but regrowth of the cell culture was also detected 10 days after treatment.…”

Section: Discussionmentioning

confidence: 99%

Dual-Functionalized Nanoliposomes Achieve a Synergistic Chemo-Phototherapeutic Effect

Lázaro-Carrillo

Rodríguez-Amigo

Mora

et al. 2022

IJMS

View full text Add to dashboard Cite

The enhancement of photodynamic therapy (PDT) effectiveness by combining it with other treatment modalities and improved drug delivery has become an interesting field in cancer research. We have prepared and characterized nanoliposomes containing the chemotherapeutic drug irinotecan (CPT11lip), the photodynamic agent protoporphyrin IX (PpIXlip), or their combination (CPT11-PpIXlip). The effects of individual and bimodal (chemo-phototherapeutic) treatments on HeLa cells have been studied by a combination of biological and photophysical studies. Bimodal treatments show synergistic cytotoxic effects on HeLa cells at relatively low doses of PpIX/PDT and CPT11. Mechanistic cell inactivation studies revealed mitotic catastrophe, apoptosis, and senescence contributions. The enhanced anticancer activity is due to a sustained generation of reactive oxygen species, which increases the number of double-strand DNA breaks. Bimodal chemo-phototherapeutic liposomes may have a very promising future in oncological therapy, potentially allowing a reduction in the CPT11 concentration required to achieve a therapeutic effect and overcoming resistance to individual cancer treatments.

show abstract

Mitotic Catastrophe Induced in HeLa Tumor Cells by Photodynamic Therapy with Methyl-aminolevulinate

Cited by 13 publications

References 56 publications

Abnormal expression ofH-Rasinduces S-phase arrest and mitotic catastrophe in human T-lymphocyte leukemia

Abnormal expression ofH-Rasinduces S-phase arrest and mitotic catastrophe in human T-lymphocyte leukemia

Verification of 5-Aminolevurinic Radiodynamic Therapy Using a Murine Melanoma Brain Metastasis Model

Dual-Functionalized Nanoliposomes Achieve a Synergistic Chemo-Phototherapeutic Effect

Contact Info

Product

Resources

About