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Publication
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| Title of Article |
Cucurbitacin B induces mitochondrial-mediated apoptosis pathway in cholangiocarcinoma cells via suppressing focal adhesion kinase signaling
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| Date of Acceptance |
12 November 2018 |
| Journal |
| Title of Journal |
Naunyn-Schmiedeberg's Archives of Pharmacology |
| Standard |
SCOPUS |
| Institute of Journal |
Springer-Verlag GmbH Germany, part of Springer Nature |
| ISBN/ISSN |
0028-1298 |
| Volume |
392 |
| Issue |
3 |
| Month |
march |
| Year of Publication |
2019 |
| Page |
271-278 |
| Abstract |
Low efficacy and high resistance rate associated with existing chemotherapeutic drugs enforce a requirement for novel therapeutic strategies for extremely aggressive cholangiocarcinoma (CCA). In the present study, the apoptosis-inducing activity of cucurbitacin B, a compound derived from plants of Cucurbitaceae family, against KKU-100 CCA cells and the underlying mechanism mediating its effect were investigated. The results showed that cucurbitacin B significantly decreased CCA cells viability by induction of apoptosis. Increased apoptotic cell death following cucurbitacin B treatment was correlated with caspase-9andcaspase-3activations,Baxupregulation,increasedcytochromec,apoptosis-inducingfactorrelease,anddecreased Bcl-2 and Bcl-XL levels, suggesting activation of the mitochondrial-mediated apoptosis pathway. Further molecular analyses revealedthatcucurbitacinBinhibitedfocaladhesionkinase(FAK),whichisanimportantregulatoroftheapoptosisprocess,and its downstream pathway, PI3K/Akt. Knockdown of FAK expression by small interfering RNA appeared to induce CCA cell apoptosis which was accompanied with elevated level of cytochrome c and cleaved caspase-9, and decreased level of Bcl-2, phospho-PI3K, and phospho-Akt. Taken together, cucurbitacin B induces an intrinsic mitochondrial apoptosis pathway in CCA cells partly through suppression of FAK-mediated oncogenic signaling. This compound should be considered as a candidate agent for CCA treatment.
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| Keyword |
CucurbitacinB, Cholangiocarcinoma, Apoptosis, Focaladhesion kinase |
| 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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