δ-Tocotrienol sensitizes and re-sensitizes ovarian cancer cells to cisplatin via induction of G1 phase cell cycle arrest and ROS/MAPK-mediated apoptosis.
Cell Prolif
; 54(11): e13111, 2021 Nov.
Article
en En
| MEDLINE
| ID: mdl-34520051
ABSTRACT
OBJECTIVES:
Among gynaecologic malignancies, ovarian cancer (OC) represents the leading cause of death for women worldwide. Current OC treatment involves cytoreductive surgery followed by platinum-based chemotherapy, which is associated with severe side effects and development of drug resistance. Therefore, new therapeutic strategies are urgently needed. Herein, we evaluated the anti-tumour effects of Vitamin E-derived δ-tocotrienol (δ-TT) in two human OC cell lines, IGROV-1 and SKOV-3 cells. MATERIALS ANDMETHODS:
MTT and Trypan blue exclusion assays were used to assess δ-TT cytotoxicity, alone or in combination with other molecules. δ-TT effects on cell cycle, apoptosis, ROS generation and MAPK phosphorylation were investigated by flow cytometry, Western blot and immunofluorescence analyses. The synergism between δ-TT and chemotherapy was evaluated by isobologram analysis.RESULTS:
We demonstrated that δ-TT could induce cell cycle block at G1-S phase and mitochondrial apoptosis in OC cell lines. In particular, we found that the proapoptotic activity of δ-TT correlated with mitochondrial ROS production and subsequent JNK and p38 activation. Finally, we observed that the compound was able to synergize with cisplatin, not only enhancing its cytotoxicity in IGROV-1 and SKOV-3 cells but also re-sensitizing IGROV-1/Pt1 cell line to its anti-tumour effects.CONCLUSIONS:
δ-TT triggers G1 phase cell cycle arrest and ROS/MAPK-mediated apoptosis in OC cells and sensitizes them to platinum treatment, thus representing an interesting option for novel chemopreventive/therapeutic strategies for OC.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Ováricas
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Vitamina E
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Apoptosis
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Proliferación Celular
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Puntos de Control de la Fase G1 del Ciclo Celular
Límite:
Female
/
Humans
Idioma:
En
Revista:
Cell Prolif
Año:
2021
Tipo del documento:
Article
País de afiliación:
Italia