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A Tripeptide-Stabilized Nanoemulsion of Oleic Acid
Published on: February 27, 2019
Oxaliplatin-loaded nanoemulsion containing Teucrium polium L. essential oil induces apoptosis in Colon cancer cell
Waad A Al-Otaibi1, Sahar M AlMotwaa1
1Department of Chemistry, College of Science and Humanities, Shaqra University, Shaqra, Saudi Arabia.
Abstract:
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.
Insights
This study developed Teucrium polium nanoemulsion (TPO-NANO) to enhance oxaliplatin (Oxa) efficacy in colon cancer. The TPO-NANO and Oxa combination showed synergistic effects, increasing apoptosis in both wild-type and mutant p53 colon cancer cells.
Area of Science:
- Oncology
- Nanotechnology
- Pharmacology
Background:
- Oxaliplatin (Oxa) efficacy in colon cancer is limited by side effects and p53 mutations.
- Developing novel therapeutic strategies to reduce toxicity and enhance Oxa's effectiveness is crucial.
- Targeting colon cancer irrespective of p53 status requires innovative approaches.
Purpose of the Study:
- To prepare and optimize Teucrium polium essential oil nanoemulsion (TPO-NANO).
- To investigate the synergistic effect of TPO-NANO combined with Oxa on colon cancer cells with varying p53 statuses.
- To evaluate the impact of this combination therapy on cancer cell viability, apoptosis, and related molecular mechanisms.
Main Methods:
- Preparation and characterization of TPO-NANO, including size analysis after Oxa loading.
- Assessment of colon cancer cell viability and calculation of the combination index (CI).
- Microscopic examination for morphological changes, flow cytometry for apoptosis, and measurement of intracellular ROS and p53/Bax protein levels.
Main Results:
- TPO-NANO size increased slightly after Oxa loading (12.90 nm to 14.47 nm).
- The combination of Oxa and TPO-NANO demonstrated synergistic effects (CI < 1) in both HCT116 (wild-type p53) and HT-29 (mutant p53) cells.
- Combination therapy significantly increased apoptosis compared to monotherapy, involving ROS-mediated mitochondrial pathways.
Conclusions:
- TPO-NANO can be effectively loaded with Oxa.
- The Oxa + TPO-NANO combination exhibits synergistic anti-cancer activity against colon cancer cells, regardless of p53 status.
- This combination therapy offers a promising strategy to enhance Oxa's efficacy and reduce toxicity in colon cancer treatment.
