The potential antitumor effect of chrysophanol in relation to cervical cancer cells

Król

et al. 2021

Cells

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Background: The extent of morphological and ultrastructural changes in HeLa cells was assessed by optical, fluorescence and electron microscopy after exposure to various concentrations of physcion, taking into account the biological properties of the test compound. Methods: Cell viability was assessed by MTT assay, while the cell cycle, LC3 expression, apoptosis, change of mitochondrial potential, Bcl-2 protein expression level and the level of reactive oxygen species were analyzed by flow cytometry. Results: As a result of physcion encumbrance, concentration-dependent inhibition of HeLa cell viability and the G0/G1 phase of the cell cycle was observed. Activation of the lysosomal system was also revealed, which was expressed by an increased number of lysosomes, autophage vacuoles and increased expression of the LC3 protein, a marker of the autophagy process. Transmission electron microscopy and fluorescence microscopy showed that physcion induced clear changes in cervical cancer cells, especially in the structure of the nucleus and mitochondria, which correlated with the production of reactive oxygen species by the test compound and indicated the induction of the oxidative process. At the same time, the pro-apoptotic effect of physcion was demonstrated, and this mechanism was dependent on the activation of caspases 3/7 and the reduction in Bcl-2 protein expression. Conclusion: The obtained results indicate an antitumor mechanism of action of physcion, based on the induction of oxidative stress, autophagy and apoptosis.

Section: Discussionsupporting

confidence: 70%

Physcion Induces Potential Anticancer Effects in Cervical Cancer Cells

Król

et al. 2021

Cells

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“…Rhein protects the liver and exerts antifibrotic effects, and its mechanism may be related to its anti-inflammatory and antioxidant effects and ability to inhibit transforming growth factor β1 and hepatic stellate cell activation ( En-Ze et al, 2016 ). Chrysophanol can inhibit the growth of HeLa cervical cancer cells ( Trybus et al, 2021 ). Citreorosein suppresses the gene expression of proinflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β, in mouse bone marrow-derived mast cells (BMMCs) stimulated with phorbol 12-myristate 13-acetate (PMA) plus the calcium ionophore A23187 ( Lu et al, 2012 ).…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics, Tissue Distribution, and Excretion Characteristics of a Radix Polygoni Multiflori Extract in Rats

Cheng

Yuan

et al. 2022

Front. Pharmacol.

Although progress has been achieved in the pharmacological activity and toxicity of Radix Polygoni Multiflori (RPM), the chemical basis of its toxicity is still unclear. Here, we performed a multicompound pharmacokinetic analysis and investigated the tissue distribution and excretion characteristics of RPM components after oral administration in rats. The findings demonstrated that the active ingredients of the RPM extract were quickly absorbed after oral administration, with high exposure levels of emodin, 2,3,5,4′-teterahydroxystilbene-2-O-β-D-glucoside (TSG), citreorosein, torachrysone-8-O-glucoside (TG), emodin-8-O-β-D-glucoside (EG), and physcion-8-O-β-D-glucoside (PG). The tissue distributions of emodin, TSG, TG, EG, and PG were high in the liver and kidney. These components were the key contributors to the effectiveness and toxicity of RPM on the liver and kidney. Most of the active ingredients were mainly excreted through feces and bile, while a few were converted into other products in the body and excreted through urine and feces.

“…Such properties are also demonstrated by other anticancer drugs with a different mechanism of action, such as cisplatin, 47 imatinib, 48 sorafenib, 49 obatoclax, 50 etoposit, or camptothecin‐DNA damaging drugs 44 . Cytotoxic effects against tumor cell lysosomes and the property of inducing autophagy have also been shown by anthraquinones that have been the subject of our previous studies, that is, aloe‐emodin, 51 emodin, 52 chrysophanol, 53 physcion, 54 including also the rhein presented in this paper.…”

Section: Discussionmentioning

confidence: 75%

Rhein induces changes in the lysosomal compartment of HeLa cells

Król

J of Cellular Biochemistry

2022

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Rhein is an anthraquinone found in Rheum palmatum, used in Chinese medicine. Due to potential anticancer properties, the study assessed its effect on the lysosomal compartment, which indirectly influences cell death. The experiment was performed on HeLa cells by treating them with rhein at concentrations of 100-300 µM. LC3-II protein and caspase 3/7 activity, level of apoptosis, the concentration of reactive oxide species (ROS), and mitochondrial potential (Δψm) were evaluated by the cytometric method. To evaluate the permeability of the lysosomal membrane (LMP), staining with acridine orange and the assessment of activity of cathepsin D and L in the lysosomal and extralysosomal fractions were used. Cell viability was assessed by -(3-(4, 5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) (MTT) and neutral red (NR) assays. Changes in cells were also demonstrated at the level of electron, optical, confocal, and fluorescence microscopy. Inhibition of autophagy was done using chloroquine. Rhein-induced degradation processes were confirmed by an increase in the number of primary lysosomes, autophagosomes, and autolysosomes. At high concentrations, rhein caused the generation of ROS, which induced LMP expressed by quenching of acridine orange fluorescence. These results correlated with a reduction of lysosomes, as visualized in graphical modeling, with the decreased uptake of NR by lysosomes, and increased activity of cathepsin D and L in the extralysosomal fraction. The studies also showed an increase in the activity of caspase 3/7 and a decrease in the expression of Bcl-2 protein, indicative of rhein-stimulated apoptosis. At the same time, we demonstrated that preincubation of cells with chloroquine inhibited rhein-induced autophagy and contributed to increased cytotoxicity to HeLa cells. Rhein also induced DNA damage and led to cycle arrest in the S phase. Our results indicate that rhein, by inducing changes in the lysosomal compartment, indirectly affects apoptosis of HeLa cells and in combination with autophagy inhibitors may be an effective form of anticancer therapy.