4.7 Article

Oxaliplatin-loaded nanoemulsion containing Teucrium polium L. essential oil induces apoptosis in Colon cancer cell lines through ROS-mediated pathway

期刊

DRUG DELIVERY
卷 29, 期 1, 页码 2190-2205

出版社

TAYLOR & FRANCIS LTD
DOI: 10.1080/10717544.2022.2096711

关键词

Oxaliplatin; Teucrium polium L; essential oil; Combination therapy; nano-delivery system; Reactive oxygen species; flow cytometry; ROS-mediated mitochondrial apoptosis; nanoemulsion

资金

  1. Deputyship for Research & Innovation, Ministry of Education in Saudi Arabia [IFP2021-016]

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This study aimed to investigate the effect of Teucrium polium L. essential oil nanoemulsion (TPO-NANO) on the sensitivity of colon cancer cells with different p53 statuses to Oxaliplatin (Oxa). The combination treatment of Oxa and TPO-NANO showed a synergistic effect on colon cancer cells, inducing apoptosis through a mechanism involving ROS-mediated mitochondrial apoptosis.
Oxaliplatin (Oxa)-associated adverse side effects have considerably limited the clinical use of the drug in colon cancer therapy. Mutant p53 has diverse mutational profiles in colon cancer, and it influences the potencies of various chemotherapeutic drugs, including Oxa. Thus, it would be highly beneficial to identify an alternative therapeutic strategy that not only reduces the toxicity of Oxa, but also exerts a synergistic effect against colon cancers, regardless of their p53 profiles. The present study was aimed at preparing and optimizing Teucrium polium L. essential oil nanoemulsion (TPO-NANO) and investigating its effect on the sensitivity of colon cancer cells with differences in p53 status (HCT116 wild-type and HT-29 mutant-type) to Oxa. The viability of treated cells was determined and the combination index (CI) was calculated. Morphological changes were determined under inverted microscopy, while percentage apoptosis was assayed using flow cytometry. Intracellular ROS and the protein levels of p53 and Bax were measured. The colony-forming potential of treated cells was determined using colony assay. The size of TPO-NANO was markedly increased from 12.90 +/- 0.04 nm to 14.47 +/- 0.53 nm after loading Oxa (p <= 0.05). The combination (Oxa + TPO-NANO) produced a synergetic effect in HCT116 and HT-29, with CI of 0.94 and 0.88, respectively. Microscopic examination and flow cytometric analysis revealed that cells treated with Oxa + TPO-NANO had a higher percentage of apoptosis than cells exposed to monotherapy. Cumulatively, Oxa exerted an apoptotic effect on wild or mutant p53 colon cancer cells when combined with TPO-NANO, through a mechanism involving ROS-mediated mitochondrial apoptosis.

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