Evaluation of lactoferrin combined hyaluronic acid formulations with the help of hyperthermia on breast cancer cell lines

Year 2024, Volume: 28 Issue: 5, 1829 - 1843, 28.06.2025

Gülengül Duman , Zeynep Güneş Tepe Demir , Fatih Kocabas , Birkan Girgin

https://izlik.org/JA92UA59CM

Abstract

Lactoferrin is a potential anticancer protein naturally found in mammalian secretions. It shows anti- proliferative effects on various cancer types in vitro and in vivo. Its activity is highly associated with the immune system and its complements. On the other hand, hyperthermia is a type of cancer therapy in which tissues are exposed to heat at a temperature in the range of 40ºC-44ºC which induces apoptosis and necrosis. Hyperthermia normally aims to improve the results of conventional treatment strategies such as chemo or radiotherapy. The study aimed to enhance the lactoferrin effect with hyperthermia. Hyaluronic acid was additionally used in the formulation to augment the anticancer effect of lactoferrin. MTT Assays were performed for cell viability at 24 and 72 hours after the lactoferrin, hyaluronic acid, and hyperthermia treatment on MCF-7, MDA-MB 231, and HDF cell lines in vitro. No anticancer efficacy of lactoferrin was observed. However, it was demonstrated that Hyaluronic acid enhanced the anti-proliferative efficacy of hyperthermia treatment, and significant reductions in the cell viability were observed after 24 hours on MCF-7 cells in a p53-dependent manner whereas no reduction in the cell viability of MDAMB 231 and HDF cells. Mutation on the p53 gene of MDA-MB 231 cells possibly prevented the heat-induced apoptosis. Hyaluronic acid-induced cell death was observed 72 hours after the treatment independently from the heat exposure group. No cytotoxicity was observed on the HDF cell line. The activity could not be obtained from the pure hyaluronic acid solution. Subsequent determination of the chemical responsible for the anticancer efficacy should be performed. This research could lead to the discovery of a new selective chemotherapeutic agent that can be used in breast cancer.

Keywords

Lactoferrin , Cell viability , Hyperthermia , Breast cancer , MTT assay

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