Physcion Induces Potential Anticancer Effects in Cervical Cancer Cells

Król

J of Cellular Biochemistry

2022

Self Cite

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.

Section: Discussionmentioning

confidence: 75%

Rhein induces changes in the lysosomal compartment of HeLa cells

Król

J of Cellular Biochemistry

2022

Self Cite

“…Additionally, Geriyol et al [ 58 ] and Mhaidat et al [ 59 ] demonstrated the genotoxic effect of Vinca alkaloids without double-stranded DNA breaks. The literature shows that other anthraquinones also exhibit genotoxicity, e.g., chrysophanol [ 60 ], physcion [ 61 ], aloe-emodin [ 62 , 63 ], danthron [ 64 ], and emodin, which is the subject of our research, and which, thanks to its structure, can easily penetrate between the adenine and thymine of the DNA double helix [ 65 ]. ATM kinase plays a key role in the response to DNA damage; however, attention is currently being paid to its important role as a modulator of oxidation (in response to stress), and as a modulator of mitochondrial homeostasis and apoptosis [ 66 ].…”

Section: Discussionmentioning

confidence: 99%

Emodin Sensitizes Cervical Cancer Cells to Vinblastine by Inducing Apoptosis and Mitotic Death

Trybus²,

Król³

2022

IJMS

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In recent years, studies on the effects of combining novel plant compounds with cytostatics used in cancer therapy have received considerable attention. Since emodin sensitizes tumor cells to chemotherapeutics, we evaluated changes in cervical cancer cells after its combination with the antimitotic drug vinblastine. Cellular changes were demonstrated using optical, fluorescence, confocal and electron microscopy. Cell viability was assessed by MTT assay. The level of apoptosis, caspase 3/7, Bcl-2 protein, ROS, mitochondrial membrane depolarization, cell cycle and degree of DNA damage were analyzed by flow cytometry. The microscopic image showed indicators characteristic for emodin- and vinblastine-induced mitotic catastrophe, i.e., multinucleated cells, giant cells, cells with micronuclei, and abnormal mitotic figures. These compounds also increased blocking of cells in the G2/M phase, and the generated ROS induced swelling and mitochondrial damage. This translated into the growth of apoptotic cells with active caspase 3/7 and inactivation of Bcl-2 protein and active ATM kinase. Emodin potentiated the cytotoxic effect of vinblastine, increasing oxidative stress, mitotic catastrophe and apoptosis. Preliminary studies show that the combined action of both compounds, may constitute an interesting form of anticancer therapy.

“…The study also showed that topical administration of red ginseng rhizomes (2 mg/mouse) and ginsenoside Ro (0.2 mg/mouse) induced hair regrowth in testosterone-treated mice [50]. Physcion, a component of Polygonum multiforum (PM), has anti-inflammatory, antioxidant, and anticancer effects [192,193]. Treatment with physcion exhibited hair growth-promoting activity in testosterone-treated C57BL/6 mice [51].…”

Section: α-Reductase Inhibitory Effectmentioning

confidence: 96%

Modulation of Hair Growth Promoting Effect by Natural Products

Park

Lee

2021

Pharmaceutics

A large number of people suffer from alopecia or hair loss worldwide. Drug-based therapies using minoxidil and finasteride for the treatment of alopecia are available, but they have shown various side effects in patients. Thus, the use of new therapeutic approaches using bioactive products to reduce the risk of anti-hair-loss medications has been emphasized. Natural products have been used since ancient times and have been proven safe, with few side effects. Several studies have demonstrated the use of plants and their extracts to promote hair growth. Moreover, commercial products based on these natural ingredients have been developed for the treatment of alopecia. Several clinical, animal, and cell-based studies have been conducted to determine the anti-alopecia effects of plant-derived biochemicals. This review is a collective study of phytochemicals with anti-alopecia effects, focusing mainly on the mechanisms underlying their hair-growth-promoting effects.