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Publication
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| Title of Article |
All‑trans‑retinoic acid induces RARB‑dependent apoptosis
via ROS induction and enhances cisplatin sensitivity
by NRF2 downregulation in cholangiocarcinoma cells |
| Date of Acceptance |
3 March 2022 |
| Journal |
| Title of Journal |
Oncology Letters |
| Standard |
ISI |
| Institute of Journal |
Spandidos Publications |
| ISBN/ISSN |
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| Volume |
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| Issue |
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| Month |
June |
| Year of Publication |
2022 |
| Page |
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| Abstract |
All-trans-retinoic acid (ATRA) has been clinically used to treat acute promyelocytic leukemia and is being studied to treat other cancers. However, the therapeutic role and mechanism of ATRA against cholangiocarcinoma (CCA) are still unclear. In the current study, we investigated the cytotoxic effect and underlying mechanisms of ATRA on CCA cell lines. ATRA induced a concentration- and time-dependent toxicity in CCA cells. When the retinoic acid receptor (RAR)-deficient cells were tested for ATRA cytotoxicity, the result showed that ATRA cytotoxicity was RARβ-dependent. Following ATRA treatment, there was a significant accumulation of cellular reactive oxygen species (ROS). ATRA-induced ROS generation led to an increase of apoptosis-inducing proteins and intrinsic apoptosis. Pretreatment with ROS scavengers could diminish the apoptosis effect of ATRA, suggesting ROS and mitochondria play an essential role in apoptosis induction. Furthermore, after ATRA treatment, an increase in cellular ROS content was associated with suppressing nuclear factor erythroid 2–related factor 2 (Nrf2) and Nrf2-downstream active genes. Moreover, ATRA also suppressed cisplatin-induced Nrf2, suggesting that the enhancement of cisplatin cytotoxicity by ATRA may be associated with the downregulation of Nrf2 signaling. The results of this study demonstrated that ATRA could be repurposed as an alternative drug for CCA therapy. |
| Keyword |
all-trans-retinoic acid, retinoic acid receptor, cholangiocarcinoma, ROS, apoptosis |
| Author |
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| Reviewing Status |
มีผู้ประเมินอิสระ |
| Status |
ตีพิมพ์แล้ว |
| Level of Publication |
นานาชาติ |
| citation |
false |
| Part of thesis |
true |
| Attach file |
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| Citation |
0
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Journal Publication
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