Cytotoxic and Metastatic Effects of Anatolian Propolis and Chemotherapeutic Agents (DOX, TAM, CLB) in 2D and 3D Breast Cancer Models

Habibe Sema Arslan; Serap Yalçın Azarkan; Gamze Turna Saltoğlu

doi:10.35206/jan.1639903

EN TR

Cytotoxic and Metastatic Effects of Anatolian Propolis and Chemotherapeutic Agents (DOX, TAM, CLB) in 2D and 3D Breast Cancer Models

Abstract

This study aims to comparatively investigate the cytotoxic and metastatic effects of Anatolian propolis and chemotherapeutic agents (Doxorubicin- DOX, Tamoxifen- TAM, Chlorambucil- CLB) on two-dimensional (2D) and three-dimensional (3D) breast cancer cell cultures. The triple-negative MDA-MB-231 breast cancer cell line was cultured in 2D and 3D models. Anatolian propolis was prepared using ethanol extraction and applied to the cells alone or in combination with chemotherapeutic agents (DOX, TAM, CLB) at their respective IC50 doses. Cytotoxicity was assessed using the XTT assay, while cell migration and invasion were evaluated using wound healing and invasion assays. Propolis, when combined with chemotherapeutic agents, significantly inhibited cell proliferation and migration (p<0.001). TAM alone exhibited an IC50 value of 0.5 µM, whereas TAM + Propolis (40 mg/mL) more effectively suppressed proliferation and migration (p<0.001). For CLB applications, the IC50 value was determined as 10 µM, and CLB+Propolis (40 mg/mL) reduced cell viability while suppressing metastatic activity (p<0.001). In 3D cultures, CLB+Propolis (80 mg/mL) disrupted spheroid integrity, preventing cancer cell dissemination (p<0.01). DOX exhibited an IC50 value of 5 µM, and DOX+Propolis (40 mg/mL) increased cell death (p<0.001). In 3D cultures, DOX+Propolis (80 mg/mL) further inhibited cell invasion by breaking down spheroid structures (p<0.001). Across all combination groups, propolis enhanced the efficacy of chemotherapeutic agents and significantly suppressed cell migration and invasion (p<0.001). The pronounced effects observed in 3D cultures suggest that propolis may act as a potent anti-metastatic agent within the tumor microenvironment. These findings indicate that propolis may serve as a complementary agent to enhance chemotherapy sensitivity; however, further preclinical and clinical studies are required to confirm its clinical applicability.

Keywords

Propolis , Doxorubicin , Tamoxifen , Chlorambucil , MDA-MB-231

Anadolu Propolisi ve Kemoterapötik Ajanların (DOX, TAM, CLB) 2B ve 3B Meme Kanseri Modellerindeki Sitotoksik ve Metastatik Etkileri

Öz

Bu çalışma, Anadolu propolisi ve kemoterapötik ajanların (Doksorubisin- DOX, Tamoksifen- TAM, Klorambusil- CLB) iki boyutlu (2B) ve üç boyutlu (3B) meme kanseri hücre kültürleri üzerindeki sitotoksik ve metastatik etkilerini karşılaştırmalı olarak incelemeyi amaçlamaktadır. Çalışmada, MDA-MB-231 üçlü negatif meme kanseri hücre hattı, 2B ve 3B kültür modellerinde geliştirilmiştir. Anadolu propolisi, etanol ekstraksiyonu yöntemiyle hazırlanmış ve belirlenen IC50 dozlarında kemoterapötik ajanlar (DOX, TAM, CLB) ile ayrı ayrı ve kombinasyon halinde hücrelere uygulanmıştır. Sitotoksisite XTT testi, hücre göçü ve invazyonu ise yara iyileştirme ve invazyon testleri ile değerlendirilmiştir. Propolis, kemoterapötik ajanlarla kombinasyon halinde uygulandığında, hücre proliferasyonunu ve migrasyonunu anlamlı şekilde baskılamıştır (p<0.001). TAM tek başına 0.5 µM IC50 değerine sahipken, TAM+Propolis (40 mg/mL) kombinasyonu proliferasyonu ve migrasyonu daha güçlü şekilde inhibe etmiştir (p<0.001). CLB uygulamalarında, IC50 değeri 10 µM olarak belirlenmiş ve CLB+Propolis (40 mg/mL) kombinasyonu hücre canlılığını azaltarak metastatik aktiviteyi baskılamıştır (p<0.001). 3B kültürde, CLB+Propolis (80 mg/mL) kombinasyonu sferoid yapıların bütünlüğünü bozarak kanser hücrelerinin yayılımını engellemiştir (p<0.01). DOX’un IC50 değeri 5 µM olarak belirlenmiş, DOX+Propolis (40 mg/mL) kombinasyonu hücre ölüm oranını artırmıştır (p<0.001). 3B kültür ortamında, DOX + Propolis (80 mg/mL) kombinasyonu sferoid yapıları parçalayarak hücre invazyonunu daha fazla inhibe etmiştir (p<0.001). Tüm kombinasyon gruplarında, propolisin kemoterapötik ajanların etkinliğini artırdığı ve hücre göçü ile invazyonu belirgin şekilde baskıladığı gözlemlenmiştir (p<0.001). Özellikle 3B kültürdeki etkiler, propolisin tümör mikroçevresinde güçlü bir anti-metastatik ajan olarak değerlendirilebileceğini göstermektedir. Bu bulgular, propolisin kemoterapiye duyarlılığı artıran tamamlayıcı bir ajan olarak değerlendirilebileceğini göstermektedir. Ancak, klinik uygulanabilirliğini doğrulamak için ileri preklinik ve klinik çalışmalara ihtiyaç duyulmaktadır.

Anahtar Kelimeler

Propolis , Doksorubisin , Tamoksifen , Klorambusil , MDA-MB-231

Kaynakça

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Ayrıntılar

Birincil Dil

İngilizce

Konular

Kimya Mühendisliği (Diğer)

Bölüm

Araştırma Makalesi

Yazarlar

Habibe Sema Arslan ^*
0000-0002-2052-9345
Türkiye

Serap Yalçın Azarkan
0000-0002-9584-266X
Türkiye

Gamze Turna Saltoğlu
0000-0002-7847-2898
Türkiye

Yayımlanma Tarihi

20 Haziran 2025

Gönderilme Tarihi

14 Şubat 2025

Kabul Tarihi

11 Mayıs 2025

Yayımlandığı Sayı

Yıl 2025 Cilt: 8 Sayı: 1

DOI

https://doi.org/10.35206/jan.1639903

IZ

https://izlik.org/JA53ZK76CY

APA

Arslan, H. S., Yalçın Azarkan, S., & Turna Saltoğlu, G. (2025). Cytotoxic and Metastatic Effects of Anatolian Propolis and Chemotherapeutic Agents (DOX, TAM, CLB) in 2D and 3D Breast Cancer Models. Journal of Apitherapy and Nature, 8(1), 103-127. https://doi.org/10.35206/jan.1639903

AMA

1.Arslan HS, Yalçın Azarkan S, Turna Saltoğlu G. Cytotoxic and Metastatic Effects of Anatolian Propolis and Chemotherapeutic Agents (DOX, TAM, CLB) in 2D and 3D Breast Cancer Models. Journal of Apitherapy and Nature. 2025;8(1):103-127. doi:10.35206/jan.1639903

Chicago

Arslan, Habibe Sema, Serap Yalçın Azarkan, ve Gamze Turna Saltoğlu. 2025. “Cytotoxic and Metastatic Effects of Anatolian Propolis and Chemotherapeutic Agents (DOX, TAM, CLB) in 2D and 3D Breast Cancer Models”. Journal of Apitherapy and Nature 8 (1): 103-27. https://doi.org/10.35206/jan.1639903.

EndNote

Arslan HS, Yalçın Azarkan S, Turna Saltoğlu G (01 Haziran 2025) Cytotoxic and Metastatic Effects of Anatolian Propolis and Chemotherapeutic Agents (DOX, TAM, CLB) in 2D and 3D Breast Cancer Models. Journal of Apitherapy and Nature 8 1 103–127.

IEEE

[1]H. S. Arslan, S. Yalçın Azarkan, ve G. Turna Saltoğlu, “Cytotoxic and Metastatic Effects of Anatolian Propolis and Chemotherapeutic Agents (DOX, TAM, CLB) in 2D and 3D Breast Cancer Models”, Journal of Apitherapy and Nature, c. 8, sy 1, ss. 103–127, Haz. 2025, doi: 10.35206/jan.1639903.

ISNAD

Arslan, Habibe Sema - Yalçın Azarkan, Serap - Turna Saltoğlu, Gamze. “Cytotoxic and Metastatic Effects of Anatolian Propolis and Chemotherapeutic Agents (DOX, TAM, CLB) in 2D and 3D Breast Cancer Models”. Journal of Apitherapy and Nature 8/1 (01 Haziran 2025): 103-127. https://doi.org/10.35206/jan.1639903.

JAMA

1.Arslan HS, Yalçın Azarkan S, Turna Saltoğlu G. Cytotoxic and Metastatic Effects of Anatolian Propolis and Chemotherapeutic Agents (DOX, TAM, CLB) in 2D and 3D Breast Cancer Models. Journal of Apitherapy and Nature. 2025;8:103–127.

MLA

Arslan, Habibe Sema, vd. “Cytotoxic and Metastatic Effects of Anatolian Propolis and Chemotherapeutic Agents (DOX, TAM, CLB) in 2D and 3D Breast Cancer Models”. Journal of Apitherapy and Nature, c. 8, sy 1, Haziran 2025, ss. 103-27, doi:10.35206/jan.1639903.

Vancouver

1.Habibe Sema Arslan, Serap Yalçın Azarkan, Gamze Turna Saltoğlu. Cytotoxic and Metastatic Effects of Anatolian Propolis and Chemotherapeutic Agents (DOX, TAM, CLB) in 2D and 3D Breast Cancer Models. Journal of Apitherapy and Nature. 01 Haziran 2025;8(1):103-27. doi:10.35206/jan.1639903

e-ISSN: 2667-4734 Yayın Modeli: Sürekli Yayın Atıf Dizinleri: TR Dizin

Cytotoxic and Metastatic Effects of Anatolian Propolis and Chemotherapeutic Agents (DOX, TAM, CLB) in 2D and 3D Breast Cancer Models

Abstract

Keywords

Anadolu Propolisi ve Kemoterapötik Ajanların (DOX, TAM, CLB) 2B ve 3B Meme Kanseri Modellerindeki Sitotoksik ve Metastatik Etkileri

Öz

Anahtar Kelimeler

Kaynakça

Ayrıntılar

Birincil Dil

Konular

Bölüm

Yazarlar

Yayımlanma Tarihi

Gönderilme Tarihi

Kabul Tarihi

Yayımlandığı Sayı

DOI

IZ

Kaynak Göster