Synergistic Effect of Caffeic Acid Phenethyl Ester and Deuterium Oxide in Colon Cancer: An In Vitro Evaluation

Darama, Gülşah; Bora, Öykü; Bostancı, Ferhat; Mehdizadehtapeh, Leila; Andaç, Serap; Tekiner, İsmail Hakki; Abdik, Hüseyin

doi:10.31557/APJCP.2026.27.6.2175

Synergistic Effect of Caffeic Acid Phenethyl Ester and Deuterium Oxide in Colon Cancer: An In Vitro Evaluation

Document Type : Research Articles

Authors

¹ Department of Nutrition and Dietetics, Istanbul Sabahattin Zaim University, Istanbul, Türkiye.

² Department of Genetics and Bioengineering, Yeditepe University, Istanbul, Türkiye.

³ Department of Molecular Biology and Genetics, Istanbul Sabahattin Zaim University, Istanbul, Türkiye.

⁴ Department of Nutrition and Dietetics, Recep Tayyip Erdoğan University, Rize, Türkiye.

⁵ Independent Researcher, Istanbul, Türkiye.

10.31557/APJCP.2026.27.6.2175

Abstract

Objective: Caffeic acid phenethyl ester (CAPE) and deuterium oxide (D2O), known as heavy water, have anticancer properties. However, their combined effects in colon cancer have not been addressed yet. This study aimed to evaluate the synergistic effects of CAPE and D2O in colon cancer using in vitro techniques. Methods: The cancer cells (HCT-116) were treated with CAPE and D2O alone and in combination to evaluate their cell viability (CV), induction of apoptosis, expression levels of tumor proliferative (AKT, NF-κB, CCND1), tumor suppressor (p16, BAX, TP53, p21) genes, and colony-forming ability, respectively. Result: The combined treatment of 10 µM CAPE and 30% D₂O in human colon cancer cells (HCT-116) were significantly: (i)cytotoxic on the CV; (i)induced apoptosis, (iii)downregulated the expression of AKT, NF-κB and CCND1 while upregulated the expression of p16, BAX, and TP53, without altering p21 level, and (iv)suppressed the cells’ colony forming ability, respectively (p<0.05). Conclusion: Overall, CAPE and D₂O may be an effective adjuvant for enhancing therapeutic efficacy in colon cancer. However, further research is needed to determine whether their synergistic effects are also selective in other malignancies, as well as with their toxicokinetic potential.

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