Ponatinib ve Türkiye’de yetişen bazı endemik bitki ekstrelerinin kombinasyonlarının meme kanseri hücreleri üzerindeki etkileri

Çağla Kayabaşı; Çığır Biray Avcı; Sunde Yılmaz Süslüer; Tuğçe Balcı Okcanoğlu; Besra Özmen Yelken; Cansu Çalışkan Kurt; Bakiye Göker Bağca; Cenk Durmuşkahya; Hüsniye Kayalar; Ahmet Özbilgin; Cumhur Gündüz

doi:10.19161/etd.1126901

EN TR

Combinational effects of ponatinib and some Turkish endemic plant extracts on breast cancer cells

Abstract

Aim: Breast cancer is the most common malignancy in women worldwide. Therefore, there is a need to define new strategies that can overcome the deficiencies of existing treatments. In our study, we aimed to define new herbal combination therapies that can be used to target breast cancer cells. For this purpose, we investigated the cytotoxic, apoptotic, anti-proliferative and cell cycle regulatory effects of Centaurea calolepis (CCI), Origanum sipyleum (OSM) and Phlomis lycia (PLI) plant extracts in combination with ponatinib on MCF-7 cells.

Materials and Methods: The cytotoxic effects of OSM, CCI, PLI and ponatinib on MCF-7 cells were measured in real time by xCELLigence. The median-effect equation was used for the analysis of combinations of ponatinib with CCI (p-CCI), OSM (p-OSM), PLI (p-PLI). Apoptosis, proliferation and cell cycle regulation were evaluated by flow cytometry.

Results: The IC50 doses of CCI, OSM and PLI extracts in MCF-7 cells were calculated as 59.5, 57, 44.2 μg/ml at 48 hours and 51.6, 54.21, 42.52 μg/ml at 72 hours, respectively. Combination analyses revealed that p-CCI was additive, p-OSM and p-PLI showed a moderate synergistic effect at 48th hours. It was determined that apoptosis induced by ponatinib was significantly increased with the combinations of CCI and PLI. CCI and PLI treatments exhibited moderate anti-proliferative effects on MCF-7 cells, while OSM extract suppressed proliferation most significantly. Consistent with the proliferation results, the highest G0/G1 arrest was observed with OSM treatment. It was revealed that combined p-CCI and p-PLI treatments significantly increased the anti-proliferative effect of ponatinib and caused a higher level of G0/G1 accumulation.

Conclusion: Combinations of ponatinib and CCI, OSM, PLI plant extracts exhibited anti-cancer activity in breast cancer with induction of apoptosis, suppression of proliferation and cell cycle arrest. In light of the high anti-cancer effects identified, extracts of these Turkish endemic plants may represent a potential strategy in the treatment of breast cancer patients.

Keywords

Ponatinib ve Türkiye’de yetişen bazı endemik bitki ekstrelerinin kombinasyonlarının meme kanseri hücreleri üzerindeki etkileri

Öz

Amaç: Meme kanseri, dünya genelinde kadınlarda en yaygın gözlenen malignansidir. Bu nedenle mevcut tedavilerin eksiklerini giderebilecek yeni stratejilerin tanımlanmasına ihtiyaç vardır. Çalışmamızda meme kanseri hücrelerinin hedeflenmesinde kullanılabilecek yeni bitkisel kombinasyon terapileri tanımlamayı hedefledik. Bu amaçla, Centaurea calolepis (CCİ), Origanum sipyleum (OSM) ve Phlomis lycia (PLİ) bitki ekstrelerinin ponatinib ile kombinasyonlarının MCF-7 hücreleri üzerindeki sitotoksik, apoptotik, anti-proliferatif ve hücre döngüsü üzerindeki etkileri araştırılmıştır.

Gereç ve Yöntem: MCF-7 hücrelerinde OSM, CCİ, PLİ ve ponatinibin sitotoksik etkileri xCELLigence ile gerçek-zamanlı olarak ölçüldü. Ponatinib ile CCİ (p-CCİ), OSM (p-OSM), PLİ (p-PLİ) kombinasyonlarının analizleri için medyan-etki denklemini kullanıldı. Apoptoz, proliferasyon, hücre döngüsü düzenlenmesi akım sitometride değerlendirildi.

Bulgular: MCF-7 hücrelerinde CCİ, OSM ve PLİ ekstrelerinin IC50 dozları sırasıyla 48. saatte 59,5, 57, 44,2 μg/ml ve 72. saatte 51,6, 54,21, 42,52 μg/ml olarak hesaplandı. Kombinasyon analizi sonuçlarına göre 48. saatte p-CCİ additif, p-OSM ve p-PLİ ılımlı sinerjistik etki sergilemekteydi. Ponatinib ile indüklenen apoptozun, CCİ ve PLİ kombinasyonlarıyla anlamlı düzeyde arttığı belirlendi. CCİ ve PLİ uygulamaları MCF-7 hücreleri üzerinde ılımlı düzeyde anti-proliferatif etki sergilerken, proliferasyonu en belirgin düzeyde OSM ekstresinin baskıladığı saptandı. Proliferasyon sonuçları ile uyumlu olarak, en yüksek G0/G1 tutulumu OSM uygulaması ile gözlendi. Kombine p-CCİ ve p-PLİ uygulamalarının ponatinibin anti-proliferatif etkisini anlamlı düzeyde arttırdıkları ve daha yüksek düzeyde G0/G1 birikimine neden oldukları ortaya koyuldu.

Sonuç: Ponatinib ile CCİ, OSM, PLİ bitki ekstrelerinin kombinasyonları apoptozu indükleyerek, proliferasyonu baskılayarak ve hücre döngüsünün durdurarak meme kanserinde anti-kanser aktivitesi sergiledi. Belirlenen yüksek anti-kanser etkilerinin ışığında, Türkiye’de yetişen bu endemik bitki ekstreleri meme kanseri tedavisinde potansiyel strateji temsil edebilir.

Anahtar Kelimeler

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Details

Primary Language

Turkish

Subjects

Health Care Administration

Journal Section

Research Article

Authors

Çağla Kayabaşı ^*
0000-0002-6797-7655
Türkiye

Çığır Biray Avcı
0000-0001-8251-4520
Türkiye

Sunde Yılmaz Süslüer
0000-0002-0535-150X
Türkiye

Tuğçe Balcı Okcanoğlu
0000-0003-0613-765X
Kuzey Kıbrıs Türk Cumhuriyeti

Besra Özmen Yelken
0000-0002-0659-1097
Türkiye

Cansu Çalışkan Kurt
0000-0003-3397-6854
Türkiye

Bakiye Göker Bağca
0000-0002-5714-7455
Türkiye

Cenk Durmuşkahya
0000-0002-8092-9770
Türkiye

Hüsniye Kayalar
0000-0001-7882-0517
Türkiye

Ahmet Özbilgin
0000-0003-3613-8741
Türkiye

Cumhur Gündüz
0000-0002-6593-3237
Türkiye

Publication Date

June 13, 2022

Submission Date

September 25, 2021

Acceptance Date

December 17, 2021

Published in Issue

Year 2022 Volume: 61 Number: 2

DOI

https://doi.org/10.19161/etd.1126901

IZ

https://izlik.org/JA29FW58JP

Cite

RIS / Bibtex

Vancouver

1.Çağla Kayabaşı, Çığır Biray Avcı, Sunde Yılmaz Süslüer, Tuğçe Balcı Okcanoğlu, Besra Özmen Yelken, Cansu Çalışkan Kurt, Bakiye Göker Bağca, Cenk Durmuşkahya, Hüsniye Kayalar, Ahmet Özbilgin, Cumhur Gündüz. Ponatinib ve Türkiye’de yetişen bazı endemik bitki ekstrelerinin kombinasyonlarının meme kanseri hücreleri üzerindeki etkileri. EJM. 2022 Jun. 1;61(2):232-43. doi:10.19161/etd.1126901