Control of tumor angiogenesis and metastasis through modulation of cell redox state

Serrano, José Joaquín; Delgado, Belén Pérez; Medina, Miguel Ángel

doi:10.1016/j.bbcan.2020.188352

Cited by 12 publications

(8 citation statements)

References 205 publications

(210 reference statements)

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“…Recently, cancer treatment using natural extracts is escalating due to low toxicity and side effects (Wang et al., 2020; Wu et al., 2019). It is well known that ROS and oxidative stress caused by internal and external factors are one of the major factors in the proliferation of cancer cells (NavaneethaKrishnan et al., 2019; Serrano et al., 2020; Srinivas et al., 2019). The APLME contains agrimoniin and agrimonolide that are known to be effective in anti‐cancer and anti‐inflammatory activities.…”

Section: Discussionmentioning

confidence: 99%

The inhibitory effect of Agrimonia Pilosa methanolic extract on matrix metalloproteinases in HT1080 cells

Eom

Kim

2021

J Food Biochem

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The risk of cancer increases with aging due to the accumulation of cellular deterioration that can spread to other organs through the blood and lymphatic vessels. Therefore, the inhibition of metastasis is a major concern for the treatment of cancer. Several synthetic drugs have been developed for the treatment of various cancers. However, these drugs are effective; nonspecific action and side effects on the normal human cells limit their wide acceptance, thus demanding some potential alternative. Hence, the present study emphasizes investigating the effect of a methanolic extract of Agrimonia Pilosa (APLME) on matrix metalloproteinases (MMPs) in human fibroblast sarcoma cells. The action of APLME on MMP‐2 and MMP‐9 was investigated using gelatin zymography. APLME suppressed the activities of MMP‐2 and MMP‐9 in PMA (phorbol myristate acetate)‐treated HT1080 cells. In addition, western blot analysis and immunofluorescence were performed to investigate the effect of APLME on the expression of the proteins that are the major proteins involved in cell invasion and metastasis. APLME treatment inhibited the expression of MMP‐2 and MMP‐9 in addition to the activations of JNK, ERK, and AKT‐1. Furthermore, APLME was observed to suppress cell invasion related to metastasis using cell invasion assay. Therefore, the above findings indicate that APLME inhibits the expression activity of MMP‐2 and MMP‐9 via inactivation of ERK and JNK in addition to AKT‐1, leading to inhibiting cell invasion. Therefore, these results indicate that APLME may be used as a candidate substance for inhibiting cell invasion. Practical applications Cancer increases the cell invasion to other organs through the blood and lymphatic vessels. Cancer cells deplete the nutrients and create new blood vessels that infiltrate and metastasize to other tissues. Therefore, this present study examined the effect of Agrimonia Pilosa on cell invasion. It was found that Agrimonia Pilosa methanolic extract inhibited the invasion of cancer cells through the inactivation of ERK and JNK. In addition, APLME reduced the activation and protein expression of MMP‐2 and MMP‐9 in addition to AKT‐1. Thus, APLME can be utilized as a potential alternative therapeutic agent for inhibiting metastasis.

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Section: Discussionmentioning

confidence: 99%

The inhibitory effect of Agrimonia Pilosa methanolic extract on matrix metalloproteinases in HT1080 cells

Eom

Kim

2021

J Food Biochem

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“…ROS accumulation can result in excessive oxidative reactions, leading to DNA, protein and lipid damage. [22] MDA (malondialdehyde) levels reflect the oxidative lipid damage caused by oxidative stress at the cellular level. Hence, we determined the MDA levels in HeLa cells.…”

Section: Lipid Peroxidation Induced By 1c In Hela Cellsmentioning

confidence: 99%

Design, Synthesis, and Anticancer Activity of Cinnamoylated Barbituric Acid Derivatives

Liu

et al. 2022

Chemistry & Biodiversity

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This work deals with the design and synthesis of 18 barbituric acid derivatives bearing 1,3‐dimethylbarbituric acid and cinnamic acid scaffolds to find potent anticancer agents. The target molecules were obtained through Knoevenagel condensation and acylation reaction. The cytotoxicity was assessed by the MTT assay. Flowcytometry was performed to determine the cell cycle arrest, apoptosis, ROS levels and the loss of MMP. The ratios of GSH/GSSG and the MDA levels were determined by using UV spectrophotometry. The results revealed that introducing substitutions (CF3, OCF3, F) on the meta‐ of the benzyl ring of barbituric acid derivatives led to a considerable increase in the antiproliferative activities compared with that of corresponding ortho‐ and para‐substituted barbituric acid derivatives. Mechanism investigation implied that the 1c could increase the ROS and MDA level, decrease the ratio of GSH/GSSG and MMP, and lead to cell cycle arrest. Further research is needed for structural optimization to enhance hydrophilicity, thereby improve the biological activity of these compounds.

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“…Oxidoreduction reactions and processes pervade biology at several levels: biosensors such as the NAD(P)+/NAD(P)H ratio for metabolic status, oxidoreductases involved in many biochemical reactions, and essential bioenergetic processes based on electron transfer reactions [38]. A redox balance is always broken by bursting ROS, which are the results of reduced free-radical-scavenging enzymes and elevated intracellular oxidant production [39].…”

Section: Ros Bursting After Trxr Inhibition By Arsenicalsmentioning

confidence: 99%

1,3-Benzodioxole Derivatives Improve the Anti-Tumor Efficiency of Arsenicals

Shi

She

Liu

et al. 2022

IJMS

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Arsenicals have been widely used in the treatment of cancers such as leukemia and other tumors. However, their side effects limit their clinical application. Stiripentol, a second-line adjunctive treatment for epilepsy with a good safety profile, inhibits microsomal cytochrome-P450-family enzymes to extend the retention time of co-administration. Inspired by the metabolism of stiripentol, the 1,3-benzodioxole responsible for the inhibition and its metabolic derivatives were conjugated with arsenical precursors. The fabricated arsenicals were eliminated much slower in mice and maintained an efficient concentration in the blood for a longer time than that of the arsenical precursors. They also performed better in anti-proliferation by inhibiting the thioredoxin system to induce oxidative stress, and concomitantly to initiate apoptosis in vitro and in vivo. The fabricated arsenicals reversed the hemogram of tumor-bearing mice to normal and eliminated the tumor without causing damage to any organs, exhibiting a good design strategy and pre-clinical application for leukemia and other tumors.

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Control of tumor angiogenesis and metastasis through modulation of cell redox state

Cited by 12 publications

References 205 publications

The inhibitory effect of Agrimonia Pilosa methanolic extract on matrix metalloproteinases in HT1080 cells

The inhibitory effect of Agrimonia Pilosa methanolic extract on matrix metalloproteinases in HT1080 cells

Design, Synthesis, and Anticancer Activity of Cinnamoylated Barbituric Acid Derivatives

1,3-Benzodioxole Derivatives Improve the Anti-Tumor Efficiency of Arsenicals

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