Yamogenin-Induced Cell Cycle Arrest, Oxidative Stress, and Apoptosis in Human Ovarian Cancer Cell Line
Steroidal saponins are a group of compounds with complex structures and biological activities. They have anti-inflammatory, antimicrobial, fungicidal, and antitumor properties. Yamogenin is one of the spirostane saponins and occurs in <i>Trigonella foenum-graecum</i>, <i>Asparagus...
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MDPI AG
2022-11-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/23/8181 |
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| author | Justyna Stefanowicz-Hajduk Anna Hering Magdalena Gucwa Monika Czerwińska J. Renata Ochocka |
| author_facet | Justyna Stefanowicz-Hajduk Anna Hering Magdalena Gucwa Monika Czerwińska J. Renata Ochocka |
| author_sort | Justyna Stefanowicz-Hajduk |
| collection | DOAJ |
| description | Steroidal saponins are a group of compounds with complex structures and biological activities. They have anti-inflammatory, antimicrobial, fungicidal, and antitumor properties. Yamogenin is one of the spirostane saponins and occurs in <i>Trigonella foenum-graecum</i>, <i>Asparagus officinalis</i>, and <i>Dioscorea collettii</i>. It is a stereoisomer of diosgenin—a well-known compound whose activity and mechanisms of action in cancer cells are determined. However, the antitumor effect of yamogenin is still little known, and the mechanism of action has not been determined. In this study, we evaluated the effect of yamogenin on human ovarian cancer SKOV-3 cells in vitro by determining the cellular factors that trigger cell death. The viability of the cells was assessed with a Real-Time xCELLigence system and the cell cycle arrest with flow cytometry. The activity of initiator and executioner caspases (-8, -9, and -3/7) was estimated with luminometry and flow cytometry, respectively. The mitochondrial membrane depolarization, the level of oxidative stress, and DNA damage in the yamogenin-treated cells were also evaluated by flow cytometry. Genes expression analysis at the mRNA level was conducted with Real-Time PCR. Bid activation and chromatin condensation were estimated with fluorescent microscopy. The obtained results indicate that yamogenin has cytotoxic activity in SKOV-3 cells with an IC<sub>50</sub> value of 23.90 ± 1.48 µg/mL and strongly inhibits the cell cycle in the sub-G1 phase. The compound also triggers cell death with a significant decrease in mitochondrial membrane potential, an increase in the level of oxidative stress (over two times higher in comparison to the control), and activation of caspase-8, -9, -3/7, as well as Bid. The results of genes expression indicate that the Tumor Necrosis Factor (TNF) Receptor Superfamily Members (TNF, TNFRSF10, TNFRSF10B, TNFRSF1B, and TNFRSF25), Fas Associated via Death Domain (FADD), and Death Effector Domain Containing 2 (DEDD2) were significantly upregulated and their relative expression was at least two times higher than in the control. Our work shows that yamogenin induces apoptosis in ovarian cancer cells, and both the extrinsic and mitochondrial—intrinsic pathways are involved in this process. |
| first_indexed | 2024-03-09T17:39:30Z |
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| id | doaj.art-47ece5d79fdc481da8323afb3c783386 |
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| last_indexed | 2024-03-09T17:39:30Z |
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| spelling | doaj.art-47ece5d79fdc481da8323afb3c7833862023-11-24T11:38:00ZengMDPI AGMolecules1420-30492022-11-012723818110.3390/molecules27238181Yamogenin-Induced Cell Cycle Arrest, Oxidative Stress, and Apoptosis in Human Ovarian Cancer Cell LineJustyna Stefanowicz-Hajduk0Anna Hering1Magdalena Gucwa2Monika Czerwińska3J. Renata Ochocka4Department of Biology and Pharmaceutical Botany, Medical University of Gdańsk, 80-416 Gdańsk, PolandDepartment of Biology and Pharmaceutical Botany, Medical University of Gdańsk, 80-416 Gdańsk, PolandDepartment of Biology and Pharmaceutical Botany, Medical University of Gdańsk, 80-416 Gdańsk, PolandDepartment of Biology and Pharmaceutical Botany, Medical University of Gdańsk, 80-416 Gdańsk, PolandDepartment of Biology and Pharmaceutical Botany, Medical University of Gdańsk, 80-416 Gdańsk, PolandSteroidal saponins are a group of compounds with complex structures and biological activities. They have anti-inflammatory, antimicrobial, fungicidal, and antitumor properties. Yamogenin is one of the spirostane saponins and occurs in <i>Trigonella foenum-graecum</i>, <i>Asparagus officinalis</i>, and <i>Dioscorea collettii</i>. It is a stereoisomer of diosgenin—a well-known compound whose activity and mechanisms of action in cancer cells are determined. However, the antitumor effect of yamogenin is still little known, and the mechanism of action has not been determined. In this study, we evaluated the effect of yamogenin on human ovarian cancer SKOV-3 cells in vitro by determining the cellular factors that trigger cell death. The viability of the cells was assessed with a Real-Time xCELLigence system and the cell cycle arrest with flow cytometry. The activity of initiator and executioner caspases (-8, -9, and -3/7) was estimated with luminometry and flow cytometry, respectively. The mitochondrial membrane depolarization, the level of oxidative stress, and DNA damage in the yamogenin-treated cells were also evaluated by flow cytometry. Genes expression analysis at the mRNA level was conducted with Real-Time PCR. Bid activation and chromatin condensation were estimated with fluorescent microscopy. The obtained results indicate that yamogenin has cytotoxic activity in SKOV-3 cells with an IC<sub>50</sub> value of 23.90 ± 1.48 µg/mL and strongly inhibits the cell cycle in the sub-G1 phase. The compound also triggers cell death with a significant decrease in mitochondrial membrane potential, an increase in the level of oxidative stress (over two times higher in comparison to the control), and activation of caspase-8, -9, -3/7, as well as Bid. The results of genes expression indicate that the Tumor Necrosis Factor (TNF) Receptor Superfamily Members (TNF, TNFRSF10, TNFRSF10B, TNFRSF1B, and TNFRSF25), Fas Associated via Death Domain (FADD), and Death Effector Domain Containing 2 (DEDD2) were significantly upregulated and their relative expression was at least two times higher than in the control. Our work shows that yamogenin induces apoptosis in ovarian cancer cells, and both the extrinsic and mitochondrial—intrinsic pathways are involved in this process.https://www.mdpi.com/1420-3049/27/23/8181steroidal saponinsSKOV-3 linein vitrocaspasesmitochondrial potentialtumor necrosis factor superfamily members |
| spellingShingle | Justyna Stefanowicz-Hajduk Anna Hering Magdalena Gucwa Monika Czerwińska J. Renata Ochocka Yamogenin-Induced Cell Cycle Arrest, Oxidative Stress, and Apoptosis in Human Ovarian Cancer Cell Line Molecules steroidal saponins SKOV-3 line in vitro caspases mitochondrial potential tumor necrosis factor superfamily members |
| title | Yamogenin-Induced Cell Cycle Arrest, Oxidative Stress, and Apoptosis in Human Ovarian Cancer Cell Line |
| title_full | Yamogenin-Induced Cell Cycle Arrest, Oxidative Stress, and Apoptosis in Human Ovarian Cancer Cell Line |
| title_fullStr | Yamogenin-Induced Cell Cycle Arrest, Oxidative Stress, and Apoptosis in Human Ovarian Cancer Cell Line |
| title_full_unstemmed | Yamogenin-Induced Cell Cycle Arrest, Oxidative Stress, and Apoptosis in Human Ovarian Cancer Cell Line |
| title_short | Yamogenin-Induced Cell Cycle Arrest, Oxidative Stress, and Apoptosis in Human Ovarian Cancer Cell Line |
| title_sort | yamogenin induced cell cycle arrest oxidative stress and apoptosis in human ovarian cancer cell line |
| topic | steroidal saponins SKOV-3 line in vitro caspases mitochondrial potential tumor necrosis factor superfamily members |
| url | https://www.mdpi.com/1420-3049/27/23/8181 |
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