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Parecoxib Enhances Resveratrol against Human Colorectal Cancer Cells through Akt and TXNDC5 Inhibition and MAPK

Wan-Ling Chang1, Kai-Chien Yang2, Jyun-Yu Peng1

  • 1Department of Anesthesiology, Chang Gung Memorial Hospital at Chiayi, No. 8, West Section of Jiapu Road, Chiayi County, Puzi City 613016, Taiwan.

Nutrients
|September 14, 2024
PubMed

Insights

Parecoxib enhances resveratrol's anti-cancer effects in colorectal cancer cells by inhibiting TXNDC5 and Akt signaling while boosting JNK/p38 pathways. This combination shows promise for sensitizing cancer cells to resveratrol treatment.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Colorectal cancer (CRC) remains a significant health concern globally.
  • Developing novel therapeutic strategies to overcome drug resistance is crucial.
  • Combination therapies offer potential for enhanced efficacy and reduced toxicity.

Purpose of the Study:

  • To elucidate the synergistic anti-cancer mechanisms of parecoxib and resveratrol in human colorectal cancer DLD-1 cells.
  • To investigate the molecular pathways involved in the combination's anti-proliferative and apoptosis-inducing effects.
  • To evaluate the role of TXNDC5, Akt, JNK, and p38 signaling in the observed anti-cancer activity.

Main Methods:

  • Cell viability was assessed using the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.
  • Apoptosis was analyzed via fluorescence microscopy and flow cytometry.
  • Gene overexpression, Western blot analysis were employed to study protein expression and phosphorylation.
  • Specific pathway manipulations (TXNDC5 overexpression, JNK/p38 repression) were performed.

Main Results:

  • Parecoxib potentiated resveratrol's ability to inhibit cell viability and induce apoptosis in DLD-1 cells.
  • The combination significantly enhanced apoptosis by inhibiting thioredoxin domain containing 5 (TXNDC5) expression and Akt phosphorylation.
  • Parecoxib augmented resveratrol-induced phosphorylation of c-Jun N-terminal kinase (JNK) and p38.
  • Overexpression of TXNDC5 or repression of JNK/p38 pathways partially reversed the anti-cancer effects of the combination therapy.

Conclusions:

  • Parecoxib enhances the anti-cancer efficacy of resveratrol in colorectal cancer cells through the inhibition of TXNDC5 and Akt signaling.
  • The combination therapy also involves the activation of JNK and p38 MAPK pathways.
  • Parecoxib demonstrates potential as an adjuvant therapy to sensitize colorectal cancer to resveratrol.
Keywords:
AktMAPKTXNDC5apoptosiscolorectal cancerparecoxibresveratrol

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