Oxidative stress mediates the inhibitory effects of Manzamine A on uterine leiomyoma cell proliferation and extracellular matrix deposition via SOAT inhibition

Lin, Li-Chun; Chang, Hsin-Yi; Kuo, Tzu-Ting; Chen, Hsin-Yuan; Liu, Wen-Shan; Lo, Yii-Jwu; Hsia, Shih-Min; Huang, Tsui-Chin

doi:10.1016/j.redox.2023.102861

Cited by 8 publications

(2 citation statements)

References 74 publications

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“…Também, a utilização da proteína 4 do epidídimo humano (HE4) como biomarcador de prognóstico em câncer de colo uterino (DUBEY et al, 2023). No tocante, as novidades de tratamento do CCU têm-se a utilização da Manzamine A' (esponja marinha encontrada nos recifes de coral) (LI-CHUN et al, 2023). Além da realização da radioterapia adaptativa em pacientes com câncer de colo uterino através do desenvolvimento de um algoritmo stacked-Brazilian Journal of Health Review, Curitiba, v. 6, n. 6, p. 33281-33301, nov./dec., 2023 ellipse (elipse empilhada) que segmenta rapidamente o útero por meio da ultrassonografia 3-D (US), obtido pelo sistema Clarity (MASON et al, 2020).…”

Section: Introductionunclassified

Panorama geral, fitomoléculas e inovações tecnológicas efetuadas no diagnóstico e tratamento do câncer cervical

Nazareno,

Fernandes,

Leão

et al. 2023

Braz. J. Hea. Rev.

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O câncer do colo do útero (CCU), atinge inúmeras mulheres a nível mundial, configurando-se como um problema de saúde pública. Assim, existem evidências do potencial quimiopreventivo e terapêutico das fitomoléculas, provocando inibição e apoptose em células cancerígenas. Logo, as inovações tecnológicas têm auxiliado na previsão do prognóstico do câncer cervical. O objetivo deste estudo foi descrever sobre o câncer cervical de forma geral, uso das fitomoléculas e as inovações tecnológicas aplicadas no diagnóstico e tratamento dessa neoplasia. A pesquisa foi realizada por meio de um levantamento bibliográfico utilizando as bases de dados do Google Scholar, Science Direct, Scielo, Scienc PubMed, Scopus, Web of Science, National Library of Medicine, PubMed Central e Portal CAPES nos períodos de publicação de 2003 a 2024. Os locais da busca foram em artigos científicos, teses, dentre outros. Conclui-se que o HPV é o principal fator de risco para obtenção do CCU. Para minimizar taxa de mortalidade devido ao câncer cervical decorre da adoção de medidas de prevenção primária, de diagnóstico e tratamento da neoplasia. Os fitoquímicos presentes nas plantas apresentam atividades antitumoral, com alto potencial quimiopreventivo e terapêutico contra o câncer cervical. As inovações tecnológicas aplicadas nos diagnósticos e tratamento do CCU, tem ajudado a rastrear e tratar essa neoplasia, com mais agilidade e segurança, auxiliando o profissional da saúde na tomada de decisão.

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Section: Introductionunclassified

Panorama geral, fitomoléculas e inovações tecnológicas efetuadas no diagnóstico e tratamento do câncer cervical

Nazareno,

Fernandes,

Leão

et al. 2023

Braz. J. Hea. Rev.

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“…Those links in the pathogenesis of this disease, which were previously omitted by researchers, are being actively studied. In particular, in the development of pathological changes in the myometrium, the role of oxidative stress and antioxidant mechanisms is speci�ied, which is generally a classic component of the pathogenesis for destructive and hyperplastic disorders in tissues [9][10][11][12]. Under normal conditions, the processes of tissue kinetics include free radical reactions, which under pathological conditions lead to their disorders.…”

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Levels of melatonin and some indicators of angiogenesis, antioxidant system and lipid peroxidation in blood plasma in women with uterine leiomyoma

Sokolov,

Berbets,

Kant

et al. 2024

COT

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Uterine leiomyoma is one of the most common gynaecological diseases, which often leads to loss of fertility. It is known that in this pathology, damage to the tissues of the uterus is accompanied by oxidative stress, and the mechanisms of its compensation play a decisive role in the process of myometrial regeneration, especially when performing organ-preserving operations. The aim of the study was to determine the levels of melatonin, reproductive hormones and state of angiogenesis, antioxidant system and lipid peroxidation in women of reproductive age who were diagnosed with uterine leiomyoma. Material and methods. 60 women of reproductive age with uterine leiomyoma (study group) were examined. The control group consisted of 20 healthy women of the same age group. Melatonin levels in women's blood were determined once, on an empty stomach, at 8 a.m.; the concentrations of estradiol and progesterone in the follicular phase of the menstrual cycle were also measured. The state of the angiogenesis system was studied by examining the levels of vascular endothelial growth factor (VEGF) and the content of the final metabolites of nitric oxide NO in blood plasma. The activity of the antioxidant system was assessed by blood plasma concentrations of reduced glutathione, glutathione peroxidase, and glutathione transferase. Indicators of lipid peroxidation were investigated by the content of malondialdehyde (MDA) in blood plasma and erythrocytes. Results. It was found that in the patients of the study group with leiomyoma, there was a significantly lower level of melatonin in blood plasma (111.1 ± 18.5 ng/mL) compared to the control group (153.5 ± 8.5 ng/mL), while the concentration of estradiol was almost three times higher (107.4 ± 25.3 pg/mL) compared to the control group (36.2 ± 3.2 pg/mL), and the concentration of progesterone was 1.9 times higher (2.1 ± 0.4 ng/mL compared to 1.1 ± 0.5 ng/mL in the control group). The level of VEGF in blood plasma in women with uterine leiomyoma was also higher (90.4 ± 23.6 pg/mL) compared to the control group (35.1 ± 8.3 pg/mL), as well as the concentration of final metabolites of nitric oxide, which reached 25.3 ± 5.9 pg/mL compared to 9.9 ± 3.9 pg/mL in the control group. The reduced glutathione level in the blood plasma of women with uterine leiomyoma was significantly lower (0.77 ± 0.13 µmol/L) compared to healthy women (1.02 ± 0.14 µmol/L) in the control group, while the concentrations of glutathione-S-transferase and glutathione peroxidase enzymes were higher (161.3 ± 22.3 ng/mL and 235.7 ± 35.9 ng/mL, respectively), whereas in the control group these indicators were 118.9 ± 18.0 ng/mL and 105.3 ± 41.2 ng/mL, respectively. The MDA content in women of the study group was higher, measuring 5.2 ± 0.8 nmol/L in plasma and 10.8 ± 1.1 nmol/L in erythrocytes compared to 2.3 ± 0.8 nmol/L and 5.3 ± 0.8 nmol/L in the control group, respectively. Conclusions. The levels of melatonin and reduced glutathione in the blood plasma of women with uterine leiomyoma were significantly lower, while the concentrations of estradiol, progesterone, glutathione-S-transferase, glutathione peroxidase, VEGF, final metabolites of nitric oxide, as well as the average MDA content in plasma and erythrocytes, were significantly higher compared to healthy women. In the study group, the relationship between the level of progesterone in blood plasma and the content of malondialdehyde in erythrocytes was described using a linear regression equation, which, as we suggest, indicates an activating effect of progesterone on oxidative stress mechanisms in the myometrium. In our opinion, oxidative stress in uterine leiomyoma occurs due to inadequate activity of the antioxidant system, an integral part of which is melatonin, leading to enhanced angiogenesis against the background of estrogen-induced myometrial proliferation.

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Mitochondrial disruption resulting from Cepharanthine-mediated TOM inhibition triggers ferroptosis in colorectal cancer cells

Li,

Zhang,

Huang

et al. 2024

J Cancer Res Clin Oncol

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Background Chemotherapy for colorectal cancer (CRC) urgently needs low-toxicity and highly effective phytomedicine. Cepharanthine (Cep) shown to have multiple anti-tumor effects, including colorectal cancer, whose pivotal mechanisms are not fully understood. Herein, the present work aims to reveal the impact of Cep on the mitochondrial and anti-injury functions of CRC cells. Methods The TOM70/20 expression was screened by bioinformatic databases. SW480 cells were utilized as the colorectal cancer cell model. The expression of TOM70/20 and the downstream molecules were measured by western blots (WB). The ferroptosis was analyzed using Transmission electron microscopy (TEM), C11-BODIPY, PGSK, and DCFH-DA probes, wherein the detection was performed by flow cytometry and laser confocal microscopy. The anti-cancer efficacy was conducted by CCK-8 and Annexin-V/PI assay. The rescue experiments were carried out using Fer-1 and TOM70 plasmid transfection. Results Bioinformatic data identified TOM20 and TOM70 were highly expressed in colorectal cancer, which could be down-regulated by Cep. Further findings disclosed that Cep treatment destroyed the mitochondria and inactivated the NRF2 signaling pathway, an essential pathway for resistance to ferroptosis, thereby promoting reactive oxygen species (ROS) generation in CRC cells. As a result, prominent ferroptosis could be observed in CRC cells in response to Cep, which thereby led to the reduced cell viability of cancer cells. On the contrary, recovery of TOM70 dampened the Cep-elicited mitochondria damage, ferroptosis, and anti-cancer efficacy. Conclusion In summary, Cep-mediated TOM inhibition inactivates the NRF2 signaling pathway, thereby triggering ferroptosis and achieving an anti-colorectal cancer effect. The current study provides an innovative chemotherapeutic approach for colorectal cancer with phytomedicine. Supplementary Information The online version contains supplementary material available at 10.1007/s00432-024-05974-1.

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Oxidative stress mediates the inhibitory effects of Manzamine A on uterine leiomyoma cell proliferation and extracellular matrix deposition via SOAT inhibition

Cited by 8 publications

References 74 publications

Panorama geral, fitomoléculas e inovações tecnológicas efetuadas no diagnóstico e tratamento do câncer cervical

Panorama geral, fitomoléculas e inovações tecnológicas efetuadas no diagnóstico e tratamento do câncer cervical

Levels of melatonin and some indicators of angiogenesis, antioxidant system and lipid peroxidation in blood plasma in women with uterine leiomyoma

Mitochondrial disruption resulting from Cepharanthine-mediated TOM inhibition triggers ferroptosis in colorectal cancer cells

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