Physapubescin B inhibits tumorgenesis and circumvents taxol resistance of ovarian cancer cells through STAT3 signaling.
Oncotarget
; 8(41): 70130-70141, 2017 Sep 19.
Article
in En
| MEDLINE
| ID: mdl-29050266
ABSTRACT
Ovarian cancer is the most lethal gynaecological malignancy. Recurrence and subsequent resistance to chemotherapy have become major obstacles to treating these diseases. In the present study, we showed that a natural withanolide isolated from the plant Physalis pubescens L. (Solanaceae), Physapubescin B, exhibited potent anti-tumor activity against ovarian cancer cells. Physapubescin B promoted apoptosis, induced cell-cycle arrest and inhibited invasion of ES-2 and A2780 cells. Physapubescin B treatment also resulted in suppression of the transcriptional activity of STAT3, an oncogenic transcription factor activated in many human malignancies including ovarian cancer, through disturbing the dimerization of STAT3, and thereby inhibited the nuclear translocation of Tyr705/Ser727-phosphorylated STAT3. The IL-6-stimulated activation of STAT3 and its downstream genes Cyclin D1, survivin, and Bcl-xL was also repressed by Physapubescin B. Furthermore, Physapubescin B sensitizes A2780 cells to taxol-induced cell growth inhibition in vitro. These findings strongly suggest that Physapubescin B has potential antitumor activity and may circumvent taxol resistance in human ovarian cancer cells through inhibition of aberrant activation of STAT3.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Oncotarget
Year:
2017
Document type:
Article
Affiliation country:
China
Publication country:
EEUU
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ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
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EUA
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UNITED STATES
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UNITED STATES OF AMERICA
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US
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USA