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

Yıl 2023, Cilt: 16 Sayı: 1, 138 - 154, 31.03.2023

Nihan Günay Mehmet Kuzucu

https://doi.org/10.18185/erzifbed.1224499

Öz

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.

Anahtar Kelimeler

Breast Cancer, Deinoxanthin, Tamoxifen, MDA-MB-453

Destekleyen Kurum

Erzincan Binali Yıldırım University, Scientific Research Projects Coordinatorship

Proje Numarası

FLY-2019-643

Teşekkür

This study was supported by Erzincan Binali Yıldırım University Scientific Research Projects Coordinatorship, project no. FLY-2019-643. We also thank Seda KILINÇ for providing pure denioxanthin.

Deinoksantinin HER2 Pozitif Meme Kanserinde Tamoksifenin Antiproliferatif Aktivitesi Üzerindeki Agonistik Etkileri: MDA-MB-453 Üzerine Bir In vitro Çalışma

Öz

2020 yılında dünya genelinde 684.996 kadının öldüğü tahmin edilen meme kanserinin patogenezinin iyi anlaşılması, tedavi yöntemlerinin geliştirilmesinde hayati bir rol oynamaktadır. Son yıllarda östrojen reseptörü (ER), progesteron reseptörü (PR), Epidermal Büyüme Faktör reseptörü-2 (HER2) ifade düzeyleri önemli prognostik belirteçler olmuştur.
Kombinasyonel terapi yaklaşımı, iki veya daha fazla aktif maddenin veya yöntemin kullanılmasıdır. Bu tedavi yönteminde en önemli kazanç karsinomun aynı anda birden fazla ilaca karşı direnç gösterme olasılığının düşük olması sebebiyle ilaç direnci gelişimini azaltmaktır.
Östrojen reseptörü yarışmalı ve steroid olmayan bir bileşik olan Tamoksifen, hormon reseptör pozitif meme kanseri olan hastaları tedavi etmek için yaklaşık 20 yıldır kullanılmaktadır.
Deinoksantin, radyasyona dirençli bir bakteri olan Deinococcus radiodurans'ın hücre duvarından saflaştırılan bir ksantofil türevidir. Bu ksantin türevinin bazı kanser türleri üzerinde proapoptotik ve antiproliferatif etkilere sahip olduğu bazı çalışmalarda gösterilmiştir.
Çalışma kapsamında Tamoksifen'in deinoksantin ile etkinliğinin artırılması hedeflendi. Tamoksifen ve deinoksantinin MDA-MB-453 meme kanseri hücre hattı üzerindeki sinerjik etkisini araştırmak için ACTB geni referans olarak kullanılarak; BAX, CASP-3, BCL-2 ve HER2 genlerinin ifade seviyeleri RT-qPCR yöntemi ile incelenmiştir. BAX, CASP-3, BCL-2 ve HER2 proteinlerinin miktarları ELISA yöntemi ile belirlenmiş ve RT-qPCR sonuçları ile karşılaştırılmıştır. Tamoksifenin HER2 pozitif meme kanseri hücre hattı üzerindeki antiproliferatif etkisinin deinoksantin kombinasyonu ile arttığı belirlendi.

Anahtar Kelimeler

Meme Kanseri, Deinoksantin, Tamoksifen, MDA-MB-453

Proje Numarası

FLY-2019-643

Kaynakça

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