Gene expression analysis of cell death induction by Ficus carica in different malignant cell lines

Tuğba Yalçınkaya; Elif Ercan; Ahmet Çarhan

doi:10.12991/jrespharm.1708971

Gene expression analysis of cell death induction by Ficus carica in different malignant cell lines

Abstract

Ficus carica (fig) has been shown to possess properties that induce cell death, making it a potential anti-cancer agent; however, its mechanism of action remains largely unknown. This study aims to identify potential common apoptotic, necrotic, and autophagic gene expression changes following Ficus carica treatment in different tumor cell lines. Two different malignant cell lines (HT-29, MG-63) were used to examine the effects of F. carica extract on cell death pathway genes. The effect of the extract on cell viability was determined in our previous study using the MTT assay. Cells were treated with the F. carica extract according to the determined IC50 dose and time point. Apoptotic, necrotic, and autophagic gene expression changes were confirmed by qRT-PCR. F. carica treatment induced apoptosis, autophagy, and necrosis in different cell lines. Among the genes with the strongest regulation of cell death-related expression, we identified pro-apoptotic (Caspase-3, Bad), autophagic (LC3-II, Atg-5), and necrotic (RIP1, RIP3) transcription factors. These pathways were found to interact each other. The results indicate that F. carica activates different types of cell death in cancer cell lines without exhibiting cytotoxic effects on healthy cells. This study represents the first combined analysis of potential target genes in apoptosis, necrosis, and autophagy pathways following F. carica treatment across two different malignant cell lines. The findings demonstrate that F. carica is an effective anti-cancer agent capable of inducing various cell death pathways.

Keywords

Supporting Institution

Ankara Yildirim Beyazit University (Ankara, Türkiye)

Project Number

BAP4169

Ethical Statement

This study does not require Ethics Committee Approval.

References

[1] M. Ergül, M. Ergül, N. Eruygur, M. Ataş, and E. Uçar, “In vitro evaluation of the chemical composition and various biological activities of ficus carica leaf extracts,” Turk J Pharm Sci, vol. 16, no. 4, 2019. http://doi.org/10.4274/tjps.galenos.2018.70037.
[2] M. N. Park et al., “Review of natural product-derived compounds as potent antiglioblastoma drugs,” 2017. http://doi.org/10.1155/2017/8139848.
[3] M. I. Barolo, N. Ruiz Mostacero, and S. N. López, “Ficus carica L. (Moraceae): An ancient source of food and health,” 2014. http://doi.org/10.1016/j.foodchem.2014.04.112.
[4] T. Omara et al., “Medicinal Plants Used in Traditional Management of Cancer in Uganda: A Review of Ethnobotanical Surveys, Phytochemistry, and Anticancer Studies,” 2020. http://doi.org/10.1155/2020/3529081.
[5] M. R. Morovati, M. Ghanbari-Movahed, E. M. Barton, M. H. Farzaei, and A. Bishayee, “A systematic review on potential anticancer activities of Ficus carica L. with focus on cellular and molecular mechanisms,” Phytomedicine, vol. 105, p. 154333, Oct. 2022. http://doi.org/10.1016/j.phymed.2022.154333.
[6] T. Yalcinkaya, L. D. Kozaci, and A. Carhan, “Ficus carica extract causes cell cycle arrest and induces apoptosis in MG-63 and HT-29 cancer cell lines,” Turkish Bulletin of Hygiene and Experimental Biology, vol. 80, no. 1, pp. 73–88, 2023. http://doi.org/10.5505/TurkHijyen.2023.93357.
[7] Y. Zhang, Y. Wan, B. Huo, B. Li, Y. Jin, and X. Hu, “Extracts and components of ficus carica leaves suppress survival, cell cycle, and migration of triple-negative breast cancer MDA-MB-231 cells,” Onco Targets Ther, vol. 11, 2018. http://doi.org/10.2147/OTT.S171601.
[8] K. Mustafa et al., “Screening, characterization, and in vitro-ROS dependent cytotoxic potential of extract from Ficus carica against hepatocellular (HepG2) carcinoma cells,” South African Journal of Botany, vol. 138, 2021. http://doi.org/10.1016/j.sajb.2020.12.018.

[9] A. Ou, X. Zhao, and Z. Lu, “Autophagy is involved in Ficus carica fruit extract-induced anti-tumor effects on pancreatic cancer,” Biomedicine and Pharmacotherapy, vol. 150, 2022. http://doi.org/10.1016/j.biopha.2022.112966.
[10] O. Boyacioglu, B. Kara, H. Can, T. N. Yerci, S. Yilmaz, and S. O. Boyacioglu, “Leaf Hexane Extracts of Two Turkish Fig (Ficus carica L.) Cultivars Show Cytotoxic Effects on a Human Prostate Cancer Cell Line,” Agriculture and Food Sciences Research, vol. 6, no. 1, pp. 66–70, 2019. http://doi.org/10.20448/journal.512.2019.61.66.70.
[11] B. S. Shin et al., “Latex of Ficus carica L. Induces Apoptosis Through Caspase and Bcl-2 Family in FaDu Human Hypopharynx Squamous Carcinoma Cells,” International Journal of Oral Biology, vol. 42, no. 4, pp. 183–190, Dec. 2017. http://doi.org/10.11620/IJOB.2017.42.4.183.
[12] S. B. Badgujar, V. V. Patel, A. H. Bandivdekar, and R. T. Mahajan, “Traditional uses, phytochemistry and pharmacology of Ficus carica: A review,” 2014. http://doi.org/10.3109/13880209.2014.892515.
[13] F. Peng et al., “Regulated cell death (RCD) in cancer: key pathways and targeted therapies,” Signal Transduct Target Ther, vol. 7, no. 1, p. 286, Aug. 2022. http://doi.org/10.1038/s41392-022-01110-y.
[14] M. Saddam et al., “Emerging biomarkers and potential therapeutics of the BCL-2 protein family: the apoptotic and anti-apoptotic context,” 2024. http://doi.org/10.1186/s43042-024-00485-7.
[15] M. Sadeghizade, J. Baharara, F. Salek, and E. Amini, “Assessment the Effect of Ficus carica Leaf Extract on B16F10 Melanoma Cancer Cells: The Roles of p53, Caspase-3 & Caspase-9 on Induction of Intrinsic Apoptosis Cascade,” Jundishapur J Nat Pharm Prod, vol. 17, no. 2, Oct. 2021. http://doi.org/.10.5812/jjnpp.117429.
[16] R. Purnamasari, D. Winarni, A. A. Permanasari, E. Agustina, S. Hayaza, and W. Darmanto, “Anticancer Activity of Methanol Extract of Ficus carica Leaves and Fruits Against Proliferation, Apoptosis, and Necrosis in Huh7it Cells,” Cancer Inform, vol. 18, pp. 0–6, 2019. http://doi.org/10.1177/1176935119842576.
[17] E. Yang, J. Zha, J. Jockel, L. H. Boise, C. B. Thompson, and S. J. Korsmeyer, “Bad, a heterodimeric partner for Bcl-xL and Bcl-2, displaces bax and promotes cell death,” Cell, vol. 80, no. 2, pp. 285–291, Jan. 1995. http://doi.org/10.1016/0092-8674(95)90411-5.
[18] R. M. Mohammad et al., “Broad targeting of resistance to apoptosis in cancer,” Semin Cancer Biol, vol. 35, pp. S78–S103, Dec. 2015. http://doi.org/10.1016/j.semcancer.2015.03.001.
[19] E. White, “The role for autophagy in cancer,” Journal of Clinical Investigation, vol. 125, no. 1, pp. 42–46, Jan. 2015. http://doi.org/10.1172/JCI73941.
[20] N. Mizushima and M. Komatsu, “Autophagy: Renovation of Cells and Tissues,” Cell, vol. 147, no. 4, pp. 728–741, Nov. 2011. http://doi.org/10.1016/j.cell.2011.10.026.
[21] Y. Liu et al., “RIP1/RIP3-regulated necroptosis as a target for multifaceted disease therapy (Review),” Int J Mol Med, Jun. 2019. http://doi.org/10.3892/ijmm.2019.4244.
[22] G. El Fawal, S. E. Sobhy, and E. E. Hafez, “Biological activities of fig latex -loaded cellulose acetate/poly(ethylene oxide) nanofiber for potential therapeutics: Anticancer and antioxidant material,” Int J Biol Macromol, vol. 270, no. May, 2024. http://doi.org/10.1016/j.ijbiomac.2024.132176.
[23] A. Saghazadeh, “Exploring the pharmacological versatility of ficus carica: Modulating classical immunometabolism and beyond,” Pharmacol Res, vol. 198, no. November, p. 107010, 2023. http://doi.org/10.1016/j.phrs.2023.107010.
[24] V. Nikoletopoulou, M. Markaki, K. Palikaras, and N. Tavernarakis, “Crosstalk between apoptosis, necrosis and autophagy,” 2013. http://doi.org/10.1016/j.bbamcr.2013.06.001.
[25] P. Vandenabeele, W. Declercq, F. Van Herreweghe, and T. Vanden Berghe, “The Role of the Kinases RIP1 and RIP3 in TNF-Induced Necrosis,” Sci Signal, vol. 3, no. 115, Mar. 2010. http://doi.org/10.1126/scisignal.3115re4.

Details

Primary Language

English

Subjects

Pharmacology and Pharmaceutical Sciences (Other)

Journal Section

Research Article

Authors

Tuğba Yalçınkaya
0000-0001-6333-7784
Türkiye

Elif Ercan
0000-0001-8120-5849
Türkiye

Ahmet Çarhan ^*
0000-0003-1584-0072
Türkiye

Publication Date

May 11, 2026

Submission Date

May 29, 2025

Acceptance Date

October 8, 2025

Published in Issue

Year 2026 Volume: 30 Number: 3

DOI

https://doi.org/10.12991/jrespharm.1708971

IZ

https://izlik.org/JA96PF54DJ

Cite

RIS / Bibtex

APA

Yalçınkaya, T., Ercan, E., & Çarhan, A. (2026). Gene expression analysis of cell death induction by Ficus carica in different malignant cell lines. Journal of Research in Pharmacy, 30(3), 853-867. https://doi.org/10.12991/jrespharm.1708971

AMA

1.Yalçınkaya T, Ercan E, Çarhan A. Gene expression analysis of cell death induction by Ficus carica in different malignant cell lines. J. Res. Pharm. 2026;30(3):853-867. doi:10.12991/jrespharm.1708971

Chicago

Yalçınkaya, Tuğba, Elif Ercan, and Ahmet Çarhan. 2026. “Gene Expression Analysis of Cell Death Induction by Ficus Carica in Different Malignant Cell Lines”. Journal of Research in Pharmacy 30 (3): 853-67. https://doi.org/10.12991/jrespharm.1708971.

EndNote

Yalçınkaya T, Ercan E, Çarhan A (May 1, 2026) Gene expression analysis of cell death induction by Ficus carica in different malignant cell lines. Journal of Research in Pharmacy 30 3 853–867.

IEEE

[1]T. Yalçınkaya, E. Ercan, and A. Çarhan, “Gene expression analysis of cell death induction by Ficus carica in different malignant cell lines”, J. Res. Pharm., vol. 30, no. 3, pp. 853–867, May 2026, doi: 10.12991/jrespharm.1708971.

ISNAD

Yalçınkaya, Tuğba - Ercan, Elif - Çarhan, Ahmet. “Gene Expression Analysis of Cell Death Induction by Ficus Carica in Different Malignant Cell Lines”. Journal of Research in Pharmacy 30/3 (May 1, 2026): 853-867. https://doi.org/10.12991/jrespharm.1708971.

JAMA

1.Yalçınkaya T, Ercan E, Çarhan A. Gene expression analysis of cell death induction by Ficus carica in different malignant cell lines. J. Res. Pharm. 2026;30:853–867.

MLA

Yalçınkaya, Tuğba, et al. “Gene Expression Analysis of Cell Death Induction by Ficus Carica in Different Malignant Cell Lines”. Journal of Research in Pharmacy, vol. 30, no. 3, May 2026, pp. 853-67, doi:10.12991/jrespharm.1708971.

Vancouver

1.Tuğba Yalçınkaya, Elif Ercan, Ahmet Çarhan. Gene expression analysis of cell death induction by Ficus carica in different malignant cell lines. J. Res. Pharm. 2026 May 1;30(3):853-67. doi:10.12991/jrespharm.1708971