Pirarubicin, an Anthracycline Anticancer Agent, Induces Apoptosis Through Generation of Hydrogen Peroxide

Mizutani, Hideki; Hotta, Saki; Nishimoto, Ayano; Ikemura, Kenji; Miyazawa, Daisuke; Ikeda, Yoshiaki; Maeda, Tohru; Yoshikawa, Masae; Hiraku, Yusuke; Kawanishi, Shosuke

doi:10.21873/anticanres.12054

Cited by 12 publications

(10 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, these observations can be explained by the mediation of H 2 O 2 production in the apoptotic mechanism induced ACR. Our previous reports have shown that doxorubicin and pirarubicin induce oxidative DNA damage by H 2 O 2 production, followed by mitochondrial dysfunction and subsequent activation of caspase-3/7, resulting in apoptosis (16,24). Therefore, these observations show the possibility that oxidative DNA damage by H 2 O 2 production induces apoptosis.…”

Section: Discussionmentioning

confidence: 62%

“…HP100 cells have approximately 340-fold higher resistance to H 2 O 2 (14) and 18 times higher catalase activity (15) than HL-60 cells. By use of HP100 cells, effects of intracellular catalase can be evaluated (16). HL-60 and HP100 cells were grown in RPMI 1640 (FUJIFILM Wako Pure Chemical Co.) supplemented with 6% fetal bovine serum (Biowest Co., Nuaillé, France) at 37˚C under 5% CO 2 in a humidified atmosphere.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Oxidative DNA Damage and Apoptosis Induced by Aclarubicin, an Anthracycline: Role of Hydrogen Peroxide and Copper

Mizutani¹,

Hayashi²,

Hashimoto³

et al. 2019

Anticancer Res

View full text Add to dashboard Cite

Background/Aim: This study aimed to investigate aclarubicin (ACR)-induced oxidative DNA damage and apoptosis. Materials and Methods: ACR-induced apoptosis was analyzed using HL-60 leukemia cells and HP100 cells, hydrogen peroxide (H 2 O 2 )-resistant cells derived from HL-60 cells. ACR-induced DNA damage was analyzed using plasmid DNA. Results: HL-60 cells were more sensitive to ACR than HP100 cells. In HP100 cells, DNA ladder formation and caspase-3/7 activity induced by ACR were suppressed or delayed in comparison to those in HL-60 cells. ACR-induced DNA damage occurred in the presence of Cu(II), and scavenger experiments showed that the reactive species causing DNA damage appeared to be generated from H 2 O 2 and Cu(I). Moreover, we detected intracellular Cu(I) induced by ACR in HL-60 cells, using CopperGREEN™, a fluorescent probe for detection of Cu(I) ion specifically. Conclusion: ACR-induced DNA damage and apoptosis can be accounted for by the involvement of H 2 O 2 and Cu(I).

show abstract

Section: Discussionmentioning

confidence: 62%

Section: Methodsmentioning

confidence: 99%

Oxidative DNA Damage and Apoptosis Induced by Aclarubicin, an Anthracycline: Role of Hydrogen Peroxide and Copper

Mizutani¹,

Hayashi²,

Hashimoto³

et al. 2019

Anticancer Res

View full text Add to dashboard Cite

show abstract

“…In both cases, doxorubicin-induced ROS production is likely to set off an apoptotic cascade in heart cells [19]. In this fashion, as is the case for mammalian endothelial cells [15], as well as a variety of human tumor cell lines [18,37], it is the production of H 2 O 2 by doxorubicin (a process modulated by the GSHPx that is present in both cytosol and mitochondria) that plays a critical role in the initiation of cardiac apoptosis. It has been demonstrated previously, furthermore, that a doxorubicin-induced peroxide flux in mammalian cells precedes the loss of mitochondrial membrane permeability that is an initiating event in anthracycline-related activation of the apoptotic cascade [18].…”

Section: Discussionmentioning

confidence: 99%

Control of doxorubicin-induced, reactive oxygen-related apoptosis by glutathione peroxidase 1 in cardiac fibroblasts

Doroshow

Esworthy

Chu

2020

Biochemistry and Biophysics Reports

View full text Add to dashboard Cite

Reactive oxygen formation plays a mechanistic role in the cardiotoxicity of doxorubicin, a chemotherapeutic agent that remains an important component of treatment programs for breast cancer and hematopoietic malignancies. To examine the role of doxorubicin-induced reactive oxygen species (ROS) in drug-related cardiac apoptosis, murine embryonic fibroblast cell lines were derived from the hearts of glutathione peroxidase 1 (Gpx-1) knockout mice. Cells from homozygous Gpx-1 knockout mice and parental animals were propagated with (Se+) and without (Se-) 100 nM sodium selenite. Activity levels of the peroxide detoxifying selenoprotein glutathione peroxidase (GSHPx) were marginally detectable (<1.6 nmol/min/mg) in fibroblasts from homozygous knockout animals whether or not cells were supplemented with selenium. GSHPx activity in Se- cells from parental murine fibroblasts was also <1.6 nmol/min/mg, whereas GSHPx levels in Se+ parental murine fibroblasts were 12.9 ± 2.7 nmol/min/mg (mean ± SE; P < 0.05). Catalase, superoxide dismutase, glutathione reductase, glutathione S-transferase, glucose 6-phosphate dehydrogenase, and reduced glutathione activities did not differ amongst the four cell lines. Reactive oxygen production increased from 908 ± 122 (arbitrary units) for untreated control cells to 1668 ± 54 following exposure to 1 μM doxorubicin for 24 h in parental fibroblasts not supplemented with selenium (P < 0.03); reactive oxygen formation in doxorubicin-treated parental fibroblasts propagated in selenium was 996 ± 69 (P = not significant compared to untreated control cells). Reactive oxygen levels in homozygous Gpx-1 knockout fibroblasts, irrespective of selenium supplementation status, were increased and equivalent to that in selenium deficient wild type fibroblasts. When cardiac fibroblasts were exposed to doxorubicin (0.05 μM) for 96 h and examined for cell cycle alterations by flow cytometry, and apoptosis by TUNEL assay, marked G2 arrest and TUNEL positivity were observed in knockout fibroblasts in the presence or absence of supplemental selenium, and in parental fibroblasts propagated without selenium. Parental fibroblasts propagated with selenium and exposed to the same concentration of doxorubicin demonstrated modest TUNEL positivity and substantially diminished amounts of low molecular weight DNA. These results were replicated in cardiac fibroblasts exposed to doxorubicin (1–2 μM) for 2 h (to mimic clinical drug dosing schedules) and examined 96 h following initiation of drug exposure. Doxorubicin uptake in cardiac fibroblasts was similar irrespective of the mRNA expression level or activity of GSHPx. These experiments suggest that the intracellular levels of doxorubicin-induced reactive oxygen species (ROS) are modulated by GSHPx and play an important role in doxorubicin-related apoptosis and altered cell cycle progression in murine cardiac fibroblasts.

show abstract

“…Combined with free tubulin, tubulin can form stable microtubules to inhibits microtubule depolymerization, ultimately inhibiting the mitosis and proliferation of cells, and the drug also has certain effects of inducing apoptosis of tumor cells. Pirarubicin is an anthracycline cell cycle non-specific anti-tumor drug that can be directly inserted between DNA double strands to inhibits DNA polymerase,20 prevent nucleic acid synthesis, and prevent cells from dividing in G2 phase, finally leading tumor cell to death. It is also effective for those who are resistant to doxorubicin.…”

Section: Discussionmentioning

confidence: 99%

Neoadjuvant chemotherapy in combination with surgery in the treatment of local advanced breast cancer

Zhao

Zhang

et al. 2019

Pak J Med Sci

View full text Add to dashboard Cite

Objective: To investigate the effect of neoadjuvant chemotherapy combined with surgery on locally advanced breast cancer and its prognosis. Methods: One hundred and fifty-four patients with locally advanced breast cancer who were admitted to our hospital from February 2014 to April 2015 were selected as the study subjects. They were divided into an observation group and a control group according to the principle of random equalization, 77 each group. The observation group was treated with TAC scheme, neoadjuvant chemotherapy combined with modified radical resection, and continuously treated with the same scheme after operation until the end of the course of treatment. The control group was treated with modified radical resection and TAC scheme. The clinical efficacy of the two groups was observed, and the perioperative indications, prognosis and occurrence of adverse reactions were compared between the two groups. Results: The total effective rate of the observation group was 76.62%, significantly higher than that of the control group (55.84%, P<0.05). The observation group had shorter operation time and hospitalization time and less bleeding amount compared to the control group (P<0.05). The metastasis rate and recurrence rate of the observation group were significantly lower than those of the control group (P<0.05); there was a significant difference between the two groups (P<0.05). The one-year and three-year survival rates of the observation group were significantly higher than those of the control group (P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups after operation (P>0.05). Conclusion: Preoperative neoadjuvant chemotherapy in combination with TAC scheme can reduce the difficulty of operation, improve the curative effect of patients, significantly improve the prognosis of patients and prolong the survival time, which is worth clinical application. doi: https://doi.org/10.12669/pjms.35.5.310 How to cite this:Zhao H, Zhang J, Lu Y, Jin J. Neoadjuvant chemotherapy in combination with surgery in the treatment of local advanced breast cancer. Pak J Med Sci. 2019;35(5):---------. doi: https://doi.org/10.12669/pjms.35.5.310 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

show abstract

Pirarubicin, an Anthracycline Anticancer Agent, Induces Apoptosis Through Generation of Hydrogen Peroxide

Abstract: Abstract. Background/Aim: Pirarubicin (THP)

Cited by 12 publications

References 9 publications

Oxidative DNA Damage and Apoptosis Induced by Aclarubicin, an Anthracycline: Role of Hydrogen Peroxide and Copper

Oxidative DNA Damage and Apoptosis Induced by Aclarubicin, an Anthracycline: Role of Hydrogen Peroxide and Copper

Control of doxorubicin-induced, reactive oxygen-related apoptosis by glutathione peroxidase 1 in cardiac fibroblasts

Neoadjuvant chemotherapy in combination with surgery in the treatment of local advanced breast cancer

Contact Info

Product

Resources

About