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Verbascoside Suppresses Epithelial-Mesenchymal Transition and Mitochondrial Biogenesis by Targeting Anti-senescence
Hsing-Chia Mai1,2,3, Pei-Fang Hsieh4,5, Chun-Hsien Wu1,3,4,6
1Department of Urology, E-Da Cancer Hospital, Kaohsiung, Taiwan, R.O.C.
Background/Aim:
Verbascoside, a natural phenylethanoid glycoside, has demonstrated significant therapeutic potential in castration-resistant prostate cancer (CRPC). This study aimed to elucidate the mechanistic pathways through which verbascoside exerts its antisenescence and anti-metastatic effects, focusing on epithelial-mesenchymal transition (EMT), oxidative stress response, and mitochondrial biogenesis regulation in CRPC cells.
Materials And Methods:
CRPC cell models were treated under various concentrations of verbascoside. EMT markers, oxidative stress-related proteins, mitochondrial biogenesis regulators, and proinflammatory cytokines were assessed using Western blotting and ELISA. Cellular senescence and proliferation were evaluated through analysis of p38 MAPK activation and key cell cycle regulators (p16, p21, p27, and retinoblastoma protein (Rb).
Results:
Verbascoside treatment inhibited EMT, reduced oxidative stress markers, and enhanced mitochondrial biogenesis, supporting cellular energy homeostasis. It also suppressed the secretion of proinflammatory cytokines, including interleukin (IL)-6, IL-8, and IL-1, associated with the senescence-associated secretory phenotype. Downstream signaling analysis revealed that verbascoside decreased p38 MAPK activation and down-regulated p16, p21, p27, and Rb, thereby attenuating prosenescence signaling and proliferation control.
Conclusion:
Verbascoside attenuates CRPC progression by modulating EMT, alleviating oxidative damage, enhancing mitochondrial function, and inhibiting prosenescence signaling pathways. These findings highlight its therapeutic potential for targeting senescence-related mechanisms in aggressive prostate cancer and provide a basis for future CRPC management strategies.
Insights
Verbascoside, a natural compound, combats aggressive prostate cancer by reducing cell migration, oxidative stress, and senescence. It enhances mitochondrial function and inhibits key pathways driving cancer progression.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Castration-resistant prostate cancer (CRPC) is an aggressive malignancy.
- Verbascoside, a phenylethanoid glycoside, shows therapeutic promise for CRPC.
- Mechanisms underlying verbascoside's effects require elucidation.
Purpose of the Study:
- Investigate verbascoside's antisenescence and anti-metastatic effects in CRPC.
- Elucidate verbascoside's impact on epithelial-mesenchymal transition (EMT), oxidative stress, and mitochondrial biogenesis.
- Analyze verbascoside's modulation of senescence-associated secretory phenotype (SASP) and cell cycle regulators.
Main Methods:
- CRPC cell models treated with verbascoside.
- Western blotting and ELISA to assess EMT markers, oxidative stress, mitochondrial regulators, and cytokines.
- Analysis of p38 MAPK, p16, p21, p27, and Rb for senescence and proliferation.
Main Results:
- Verbascoside inhibited EMT, reduced oxidative stress, and enhanced mitochondrial biogenesis.
- Suppressed secretion of proinflammatory cytokines (IL-6, IL-8, IL-1).
- Decreased p38 MAPK activation and down-regulated p16, p21, p27, and Rb, reducing senescence and proliferation.
Conclusions:
- Verbascoside attenuates CRPC progression via modulation of EMT, oxidative stress, mitochondrial function, and senescence pathways.
- Highlights verbascoside's potential in targeting senescence in aggressive prostate cancer.
- Provides a basis for future CRPC management strategies targeting senescence.
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