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

Yalçınkaya T., Ercan E., Çarhan A.

JOURNAL OF RESEARCH IN PHARMACY, vol.30, no.3, pp.853-867, 2026 (ESCI, Scopus, TRDizin)

  • Publication Type: Article / Article
  • Volume: 30 Issue: 3
  • Publication Date: 2026
  • Doi Number: 10.12991/jrespharm.1708971
  • Journal Name: JOURNAL OF RESEARCH IN PHARMACY
  • Journal Indexes: Scopus, Emerging Sources Citation Index (ESCI), TR DİZİN (ULAKBİM)
  • Page Numbers: pp.853-867
  • Ankara Yıldırım Beyazıt University Affiliated: Yes

Abstract

Ficus carica (fig) has been shown to possess properties that induce cell death, making it a potential anticancer 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 malignant human cell lines, HT-29 (colon cancer) and MG-63 (bone cancer), were selected for the investigation. In our previous study, the extract’s cytotoxic effects were determined using the MTT assay, and IC50 values were calculated. Based on these findings, both cell lines were treated with F. carica extract at the respective IC50 concentrations and time points. Gene expression changes associated with apoptotic (e.g., Caspase-3, BAD), autophagic (e.g., LC3- II, ATG5), and necrotic (e.g., RIPK1, RIPK3) pathways were quantified by qRT-PCR. Subsequently, protein-protein interaction networks were constructed using the STRING database, and KEGG pathway analysis was performed to identify enriched pathways and molecular interactions. 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 with 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