Agonistic Effects of Deinoxanthin on Tamoxifen Antiproliferative Activity on HER2 Positive Breast Cancer: An In vitro Study on MDA-MB-453

Abstract

A good understanding of the pathogenesis of breast cancer, in which in 2020 an estimated 684,996 women across the world died, plays a vital role in the development of treatment methods. In recent years, estrogen receptor (ER), progesterone receptor (PR), and Epidermal Growth Factor receptor-2 (HER2) expression levels have been substantial prognostic markers. The combinational therapy approach is the use of two or more active ingredients or methods. The most important benefit of this treatment method is to reduce the development of drug resistance since the probability of the carcinoma being resistant to more than one drug at the same time is low. Tamoxifen, an estrogen receptor competitive and nonsteroidal drug, has been used for nearly 20 years to treat patients with hormone receptor-positive breast cancer. Deinoxanthin is a xanthophyll derivative purified from the cell wall of a radiation-resistant bacterium, Deinococcus radiodurans. This xanthine derivative has been shown in some studies to have proapoptotic and antiproliferative effects on some types of cancer. Within the study's scope, it aimed to increase the effectiveness of Tamoxifen with deinoxanthin. Using the ACTB gene as a reference to investigate the synergistic effect of Tamoxifen and deinoxanthin on the MDA-MB-453 breast cancer cell line; Expression levels of BAX, CASP-3, BCL-2, and HER2 genes were examined by RT-qPCR method. The ELISA method determined the amounts of BAX, CASP-3, BCL-2, and HER2 proteins and compared them with RT-qPCR results. It was determined that the antiproliferative effect of Tamoxifen on the HER2 positive breast cancer cell line was increased with the combination of deinoxanthin.