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

Year 2025, , 103 - 127, 20.06.2025

Habibe Sema Arslan , Serap Yalçın Azarkan , Gamze Turna Saltoğlu

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

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

Ethical Statement

This study does not involve human participants or animal experiments. The human-derived MDA-MB-231 breast cancer cell line used in this study was obtained from [Source, e.g., ATCC], and all experimental procedures were conducted in accordance with institutional biosafety and research ethics guidelines. The authors declare that there is no conflict of interest.

Supporting Institution

Kırsehir Ahi Evran University Scientific Research Projects Coordination Unit

Project Number

TIP.A3.24.013

Thanks

This research was supported by the Kirsehir Ahi Evran University Scientific Research Projects Coordination Unit (Project No: TIP.A3.24.013).

References

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  • Altabbal, S., Athamnah, K., Rahma, A., Wali, A., Eid, A., Iratni, R., & Dhaheri, Y. A. (2023). Propolis: A detailed insight of its anticancer molecular mechanisms. Pharmaceuticals, 16. https://doi.org/10.3390/ph16030450
  • Arcamone, F., Cassinelli, G., Fantini, G., Grein, A., Orezzi, P., Pol, C., & Spalla, C. (1969). Adriamycin, 14‐hydroxydaimomycin, a new antitumor antibiotic from S. Peucetius var. caesius. Biotechnology and Bioengineering, 11(6), 1101-1110. https://doi.org/10.1002/bit.260110607
  • Bielawski, K., Bielawska, A., Muszyńska, A., Popławska, B., & Czarnomysy, R. (2011). Cytotoxic activity of G3 PAMAM-NH2 dendrimer-chlorambucil conjugate in human breast cancer cells. Environmental Toxicology and Pharmacology, 32(3), 364-372. https://doi.org/10.1016/j.etap.2011.08.002
  • Caner, A., Onal, M., & Silici, S. (2021). The effect of bee bread (Perga) with chemotherapy on MDA-MB-231 cells. Molecular Biology Reports, 48, 2299-2306. https://doi.org/10.1007/s11033-021-06259-3
  • Cortes-Funes, H., & Coronado, C. (2007). Role of anthracyclines in the era of targeted therapy. Cardiovascular Toxicology, 7, 56-60. https://doi.org/10.1007/s12012-007-0015-3
  • Duran, G. G. (2024). Investigation of apoptotic efficacy of propolis in MCF-7 cell line. Interdisciplinary Medical Journal, 15(52), 80-85. https://doi.org/10.17944/interdiscip.1466355
  • El-Kersh, D., El-Ezz, R. A., Ramadan, E., & El-Kased, R. (2024). In vitro and in vivo burn healing study of standardized propolis: Unveiling its antibacterial, antioxidant and anti-inflammatory actions in relation to its phytochemical profiling. PLOS ONE, 19. https://doi.org/10.1371/journal.pone.0302795
  • Eralp, T. N., Sevinc, A., & Mansuroglu, B. (2024). Combination therapy application of Abemaciclib with Doxorubicin in triple negative breast cancer cell line MDA-MB-231. Cellular and Molecular Biology, 70(2), 169-177. https://doi.org/10.14715/cmb/2024.70.2.24
  • Fong, E. L. S., Toh, T. B., Yu, H., & Chow, E. K.-H. (2017). 3D culture as a clinically relevant model for personalized medicine. Slas Technology: Translating Life Sciences Innovation, 22(3), 245-253. https://doi.org/10.1177/2472630317697251
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  • Gogacz, M., Peszke, J., Natorska-Chomicka, D., Ruszała, M., & Dos Santos Szewczyk, K. (2023). Anticancer Effects of Propolis Extracts Obtained Using the Cold Separation Method on Breast Cancer Cell Lines. Plants, 12(4), 884. https://doi.org/10.3390/plants12040884
  • Hashemi, J. M. (2016). Biological effect of bee propolis: A review. Eur. J. Appl. Sci, 8, 311-318. https://doi.org/10.5829/idosi.ejas.2016.311.318
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  • Kasote, D., Bankova, V., & Viljoen, A. M. (2022). Propolis: Chemical diversity and challenges in quality control. Phytochemistry Reviews, 21(6), 1887-1911. https://doi.org/10.1007/s11101-022-09816-1
  • Kim, C. Y., Kim, Y., Oh, J., & Kim, M. (2021). HOXB5 confers tamoxifen resistance in breast cancer cells and promotes tumor aggression and progression. AntiCancer Research, 41, 3409-3417. https://doi.org/10.21873/anticanres.15128
  • Kuo, W.-Y., Hwu, L., Wu, C.-Y., Lee, J.-S., Chang, C.-W., & Liu, R.-S. (2017). STAT3/NF-κB-regulated lentiviral TK/GCV suicide gene therapy for cisplatin-resistant triple-negative breast cancer. Theranostics, 7(3), 647. https://doi.org/10.7150/thno.16827
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  • Majumdar, P. (2012). Differential sensitivity evaluation of MCF-7 and MDA-MB-231 human breast cancer cells exposed to tamoxifen alone and in combination with estradiol. International Journal of Pharma and Bio Sciences. https://www.ijpbs.net/abstract.php?article=MTY4Mw==
  • Maria, R., Altei, W., Selistre-De-Araújo, H., & Colnago, L. (2017). Impact of chemotherapy on metabolic reprogramming: Characterization of the metabolic profile of breast cancer MDA‐MB‐231 cells using 1H HR‐MAS NMR spectroscopy. Journal of Pharmaceutical and Biomedical Analysis, 146, 324. https://doi.org/10.1016/j.jpba.2017.08.038
  • Mengji, R., Paladugu, D., Saha, B., & Jana, A. (2024). Single-photon deep-red light-triggered direct release of an anticancer drug: An investigative tumor regression study on a breast cancer spheroidal tumor model. Journal of Medicinal Chemistry. https://doi.org/10.1021/acs.jmedchem.4c00432
  • Montagner, D., Tolan, D., Andriollo, E., Gandin, V., & Marzano, C. (2018). A Pt(IV) prodrug combining chlorambucil and cisplatin: A dual-acting weapon for targeting DNA in cancer cells. International Journal of Molecular Sciences, 19. https://doi.org/10.3390/ijms19123775
  • Nguyen, H. X., Nguyen, M. T., Nguyen, N. T., & Awale, S. (2017). Chemical constituents of propolis from Vietnamese Trigona minor and their antiausterity activity against the PANC-1 human pancreatic cancer cell line. Journal of Natural Products, 80(8), 2345-2352. https://doi.org/10.1021/acs.jnatprod.7b00375
  • Oršolić, N., & Jazvinšćak Jembrek, M. (2022). Molecular and cellular mechanisms of propolis and its polyphenolic compounds against cancer. International Journal of Molecular Sciences, 23(18), 10479. https://doi.org/10.3390/ijms231810479
  • Pai, J.-T., Lee, Y.-C., Chen, S.-Y., Leu, Y.-L., & Weng, M.-S. (2018). Propolin C inhibited migration and invasion via suppression of EGFR-mediated epithelial-to-mesenchymal transition in human lung cancer cells. Evidence-Based Complementary and Alternative Medicine, 2018(1), 7202548. https://doi.org/10.1155/2018/7202548
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  • Popova, M., Giannopoulou, E., Skalicka-Woźniak, K., Graikou, K., Widelski, J., Bankova, V., et al. (2017). Characterization and biological evaluation of propolis from Poland. Molecules, 22(7), 1159. https://doi.org/10.3390/molecules22071159
  • Rosales, C., Zhao, J., Gutgesell, L., Xiong, R., Tonetti, D., & Thatcher, G. (2018). Abstract 3738: Three-dimensional treatment-resistant breast cancer spheroids as a predictive model of in vivo response to endocrine therapy. Endocrinology. https://doi.org/10.1158/1538-7445.AM2018-3738
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Anadolu Propolisi ve Kemoterapötik Ajanların (DOX, TAM, CLB) 2B ve 3B Meme Kanseri Modellerindeki Sitotoksik ve Metastatik Etkileri

Year 2025, , 103 - 127, 20.06.2025

Habibe Sema Arslan , Serap Yalçın Azarkan , Gamze Turna Saltoğlu

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

Abstract

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.

Keywords

Propolis Doksorubisin Tamoksifen Klorambusil MDA-MB-231

Project Number

TIP.A3.24.013

References

  • Ali, S., Rasool, M., Chaoudhry, H., Pushparaj, P. N., Jha, P., Hafiz, A., et al. (2016). Molecular mechanisms and mode of tamoxifen resistance in breast cancer. Bioinformation, 12(3), 135. https://doi.org/10.6026/97320630012135
  • Altabbal, S., Athamnah, K., Rahma, A., Wali, A., Eid, A., Iratni, R., & Dhaheri, Y. A. (2023). Propolis: A detailed insight of its anticancer molecular mechanisms. Pharmaceuticals, 16. https://doi.org/10.3390/ph16030450
  • Arcamone, F., Cassinelli, G., Fantini, G., Grein, A., Orezzi, P., Pol, C., & Spalla, C. (1969). Adriamycin, 14‐hydroxydaimomycin, a new antitumor antibiotic from S. Peucetius var. caesius. Biotechnology and Bioengineering, 11(6), 1101-1110. https://doi.org/10.1002/bit.260110607
  • Bielawski, K., Bielawska, A., Muszyńska, A., Popławska, B., & Czarnomysy, R. (2011). Cytotoxic activity of G3 PAMAM-NH2 dendrimer-chlorambucil conjugate in human breast cancer cells. Environmental Toxicology and Pharmacology, 32(3), 364-372. https://doi.org/10.1016/j.etap.2011.08.002
  • Caner, A., Onal, M., & Silici, S. (2021). The effect of bee bread (Perga) with chemotherapy on MDA-MB-231 cells. Molecular Biology Reports, 48, 2299-2306. https://doi.org/10.1007/s11033-021-06259-3
  • Cortes-Funes, H., & Coronado, C. (2007). Role of anthracyclines in the era of targeted therapy. Cardiovascular Toxicology, 7, 56-60. https://doi.org/10.1007/s12012-007-0015-3
  • Duran, G. G. (2024). Investigation of apoptotic efficacy of propolis in MCF-7 cell line. Interdisciplinary Medical Journal, 15(52), 80-85. https://doi.org/10.17944/interdiscip.1466355
  • El-Kersh, D., El-Ezz, R. A., Ramadan, E., & El-Kased, R. (2024). In vitro and in vivo burn healing study of standardized propolis: Unveiling its antibacterial, antioxidant and anti-inflammatory actions in relation to its phytochemical profiling. PLOS ONE, 19. https://doi.org/10.1371/journal.pone.0302795
  • Eralp, T. N., Sevinc, A., & Mansuroglu, B. (2024). Combination therapy application of Abemaciclib with Doxorubicin in triple negative breast cancer cell line MDA-MB-231. Cellular and Molecular Biology, 70(2), 169-177. https://doi.org/10.14715/cmb/2024.70.2.24
  • Fong, E. L. S., Toh, T. B., Yu, H., & Chow, E. K.-H. (2017). 3D culture as a clinically relevant model for personalized medicine. Slas Technology: Translating Life Sciences Innovation, 22(3), 245-253. https://doi.org/10.1177/2472630317697251
  • Ganta, S., Paxton, J. W., Baguley, B. C., & Garg, S. (2008). Pharmacokinetics and pharmacodynamics of chlorambucil delivered in parenteral emulsion. International Journal of Pharmaceutics, 360(1-2), 115-121. https://doi.org/10.1016/j.ijpharm.2008.04.027
  • Gogacz, M., Peszke, J., Natorska-Chomicka, D., Ruszała, M., & Dos Santos Szewczyk, K. (2023). Anticancer Effects of Propolis Extracts Obtained Using the Cold Separation Method on Breast Cancer Cell Lines. Plants, 12(4), 884. https://doi.org/10.3390/plants12040884
  • Hashemi, J. M. (2016). Biological effect of bee propolis: A review. Eur. J. Appl. Sci, 8, 311-318. https://doi.org/10.5829/idosi.ejas.2016.311.318
  • Iqbal, M., Fan, T.-p., Watson, D., Alenezi, S., Saleh, K., & Sahlan, M. (2019). Preliminary studies: The potential anti-angiogenic activities of two Sulawesi Island (Indonesia) propolis and their chemical characterization. Heliyon, 5(7). https://doi.org/10.1016/j.heliyon.2019.e01978
  • Jonkman, J. E., Cathcart, J. A., Xu, F., Bartolini, M. E., Amon, J. E., Stevens, K. M., & Colarusso, P. (2014). An introduction to the wound healing assay using live-cell microscopy. Cell Adhesion & Migration, 8(5), 440-451. https://doi.org/10.4161/cam.36224
  • Kartal, M., Kaya, S., & Kurucu, S. (2002). GC-MS analysis of propolis samples from two different regions of Turkey. Zeitschrift für Naturforschung C, 57(9-10), 905-909. https://doi.org/10.1515/znc-2002-9-1025
  • Kasote, D., Bankova, V., & Viljoen, A. M. (2022). Propolis: Chemical diversity and challenges in quality control. Phytochemistry Reviews, 21(6), 1887-1911. https://doi.org/10.1007/s11101-022-09816-1
  • Kim, C. Y., Kim, Y., Oh, J., & Kim, M. (2021). HOXB5 confers tamoxifen resistance in breast cancer cells and promotes tumor aggression and progression. AntiCancer Research, 41, 3409-3417. https://doi.org/10.21873/anticanres.15128
  • Kuo, W.-Y., Hwu, L., Wu, C.-Y., Lee, J.-S., Chang, C.-W., & Liu, R.-S. (2017). STAT3/NF-κB-regulated lentiviral TK/GCV suicide gene therapy for cisplatin-resistant triple-negative breast cancer. Theranostics, 7(3), 647. https://doi.org/10.7150/thno.16827
  • Liu, C.-Y., Hung, M., Wang, D.-S., Chu, P., Su, J.-C., Teng, T., . . . Chen, K.-F. (2014). Tamoxifen induces apoptosis through cancerous inhibitor of protein phosphatase 2A–dependent phospho-Akt inactivation in estrogen receptor–negative human breast cancer cells. Breast Cancer Research: BCR, 16. https://doi.org/10.1186/s13058-014-0431-9
  • Lv, D., Hu, Z., Lu, L., Lu, H., & Xu, X. (2017). Three-dimensional cell culture: A powerful tool in tumor research and drug discovery. Oncology Letters, 14(6), 6999-7010. https://doi.org/10.3892/ol.2017.7134
  • Majumdar, P. (2012). Differential sensitivity evaluation of MCF-7 and MDA-MB-231 human breast cancer cells exposed to tamoxifen alone and in combination with estradiol. International Journal of Pharma and Bio Sciences. https://www.ijpbs.net/abstract.php?article=MTY4Mw==
  • Maria, R., Altei, W., Selistre-De-Araújo, H., & Colnago, L. (2017). Impact of chemotherapy on metabolic reprogramming: Characterization of the metabolic profile of breast cancer MDA‐MB‐231 cells using 1H HR‐MAS NMR spectroscopy. Journal of Pharmaceutical and Biomedical Analysis, 146, 324. https://doi.org/10.1016/j.jpba.2017.08.038
  • Mengji, R., Paladugu, D., Saha, B., & Jana, A. (2024). Single-photon deep-red light-triggered direct release of an anticancer drug: An investigative tumor regression study on a breast cancer spheroidal tumor model. Journal of Medicinal Chemistry. https://doi.org/10.1021/acs.jmedchem.4c00432
  • Montagner, D., Tolan, D., Andriollo, E., Gandin, V., & Marzano, C. (2018). A Pt(IV) prodrug combining chlorambucil and cisplatin: A dual-acting weapon for targeting DNA in cancer cells. International Journal of Molecular Sciences, 19. https://doi.org/10.3390/ijms19123775
  • Nguyen, H. X., Nguyen, M. T., Nguyen, N. T., & Awale, S. (2017). Chemical constituents of propolis from Vietnamese Trigona minor and their antiausterity activity against the PANC-1 human pancreatic cancer cell line. Journal of Natural Products, 80(8), 2345-2352. https://doi.org/10.1021/acs.jnatprod.7b00375
  • Oršolić, N., & Jazvinšćak Jembrek, M. (2022). Molecular and cellular mechanisms of propolis and its polyphenolic compounds against cancer. International Journal of Molecular Sciences, 23(18), 10479. https://doi.org/10.3390/ijms231810479
  • Pai, J.-T., Lee, Y.-C., Chen, S.-Y., Leu, Y.-L., & Weng, M.-S. (2018). Propolin C inhibited migration and invasion via suppression of EGFR-mediated epithelial-to-mesenchymal transition in human lung cancer cells. Evidence-Based Complementary and Alternative Medicine, 2018(1), 7202548. https://doi.org/10.1155/2018/7202548
  • Patel, S. (2016). Emerging adjuvant therapy for cancer: Propolis and its constituents. Journal of Dietary Supplements, 13(3), 245-268. https://doi.org/10.3109/19390211.2015.1008614
  • Popova, M., Giannopoulou, E., Skalicka-Woźniak, K., Graikou, K., Widelski, J., Bankova, V., et al. (2017). Characterization and biological evaluation of propolis from Poland. Molecules, 22(7), 1159. https://doi.org/10.3390/molecules22071159
  • Rosales, C., Zhao, J., Gutgesell, L., Xiong, R., Tonetti, D., & Thatcher, G. (2018). Abstract 3738: Three-dimensional treatment-resistant breast cancer spheroids as a predictive model of in vivo response to endocrine therapy. Endocrinology. https://doi.org/10.1158/1538-7445.AM2018-3738
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There are 40 citations in total.

Details

Primary Language English
Subjects Chemical Engineering (Other)
Journal Section Research Articles
Authors

Habibe Sema Arslan 0000-0002-2052-9345

Serap Yalçın Azarkan 0000-0002-9584-266X

Gamze Turna Saltoğlu 0000-0002-7847-2898

Project Number TIP.A3.24.013
Publication Date June 20, 2025
Submission Date February 14, 2025
Acceptance Date May 11, 2025
Published in Issue Year 2025

Cite

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 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. J.Apit.Nat. June 2025;8(1):103-127. doi:10.35206/jan.1639903
Chicago Arslan, Habibe Sema, Serap Yalçın Azarkan, and 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 8, no. 1 (June 2025): 103-27. https://doi.org/10.35206/jan.1639903.
EndNote Arslan HS, Yalçın Azarkan S, Turna Saltoğlu G (June 1, 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 H. S. Arslan, S. Yalçın Azarkan, and G. Turna Saltoğlu, “Cytotoxic and Metastatic Effects of Anatolian Propolis and Chemotherapeutic Agents (DOX, TAM, CLB) in 2D and 3D Breast Cancer Models”, J.Apit.Nat., vol. 8, no. 1, pp. 103–127, 2025, doi: 10.35206/jan.1639903.
ISNAD Arslan, Habibe Sema et al. “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 (June 2025), 103-127. https://doi.org/10.35206/jan.1639903.
JAMA 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. J.Apit.Nat. 2025;8:103–127.
MLA Arslan, Habibe Sema et al. “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, vol. 8, no. 1, 2025, pp. 103-27, doi:10.35206/jan.1639903.
Vancouver 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. J.Apit.Nat. 2025;8(1):103-27.

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