Emodin Sensitizes Cervical Cancer Cells to Vinblastine by Inducing Apoptosis and Mitotic Death.
Wojciech TrybusEwa TrybusTeodora KrólPublished in: International journal of molecular sciences (2022)
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.
Keyphrases
- induced apoptosis
- oxidative stress
- cell cycle arrest
- cell death
- endoplasmic reticulum stress
- dna damage
- cell cycle
- diabetic rats
- signaling pathway
- pi k akt
- cell proliferation
- cancer therapy
- ischemia reperfusion injury
- deep learning
- high throughput
- mesenchymal stem cells
- bone marrow
- single molecule
- electronic health record
- single cell
- amino acid
- heat shock
- heat shock protein
- rare case