Ripe and Unripe Fig Extracts Modulate Cytotoxicity, Invasion, and Apoptosis in Colorectal Cancer Cells
Öz
Colorectal cancer (CRC) remains one of the deadliest malignancies, underscoring the need for novel therapeutic strategies. Ficus carica L. (fig) has recognized medicinal properties, yet its effects on CRC cells are insufficiently studied. This research examined the cytotoxic, anti-invasive, and apoptotic activities of ripe and unripe fig extracts. Methanol and water extracts were analyzed for total phenolic content and antioxidant capacity. Cytotoxicity against HT-29 and DLD-1 CRC cells was assessed with the Alamar Blue assay, using PNT1A prostate epithelial cells as non-malignant controls. Cell invasion was tested in Matrigel-coated transwell chambers, apoptosis by flow cytometry, and molecular changes by qRT-PCR and Western blot targeting Bax, Bcl-2, and NF-κB. The unripe-methanol extract showed the highest phenolic content and antioxidant activity but limited cytotoxicity. Conversely, the ripe-water extract suppressed CRC cell proliferation while sparing normal cells. It inhibited invasion in DLD-1 but increased it in HT-29. Apoptosis was not markedly induced in HT-29, though DLD-1 cells showed moderate increases. Gene and protein expression suggested extract-dependent modulation of apoptotic and inflammatory markers, with some discrepancies between mRNA and protein levels. Overall, these findings highlight the therapeutic promise of fig extracts and the influence of ripening stage and solvent choice.
Anahtar Kelimeler
Ficus carica, colorectal cancer, apoptosis, invasion, antioxidant activity
Destekleyen Kurum
Selçuk Üniversitesi
Proje Numarası
16202041, 17401051
Etik Beyan
Bu çalışma, yalnızca hücre hatları kullanılarak yapılan in vitro deneylere dayanmaktadır; kurumsal etik standartlara uygun olarak gerçekleştirilmiş olup, önceden etik kurul onayı gerektirmemektedir.
Teşekkür
Bu çalışma, 16202041 ve 17401051 numaralı projeler kapsamında Selçuk Üniversitesi Bilimsel Araştırma Fonu tarafından desteklenmiştir.
Kaynakça
- Abdel-Rahman, R., Ghoneimy, E., Abdel-Wahab, A., Eldeeb, N., Salem, M., Salama, E., & Ahmed, T. (2021). The therapeutic effects of Ficus carica extract as antioxidant and anticancer agent. South African Journal of Botany, 141, 273-277. DOI: 10.1016/j.sajb.2021.04.019
- Aggarwal, B. B., Banerjee, S., Bharadwaj, U., Sung, B., Shishodia, S., & Sethi, G. (2007). Curcumin induces the degradation of cyclin E expression through ubiquitin-dependent pathway and up-regulates cyclin- dependent kinase inhibitors p21 and p27 in multiple human tumor cell lines. Biochemical Pharmacology, 73 (7), 1024-1032. DOI: 10.1016/j.bcp.2006.12.010
- Brand-Williams, W., Cuvelier, M. E., & Berset, C. L. W. T. (1995). Use of a free radical method to evaluate antioxidant activity. LWT-Food science and Technology, 28(1), 25-30. DOI: 10.1016/S0023- 6438(95)80008-5
- Chau, I., & Cunningham, D. (2006). Adjuvant therapy in colon cancer-what, when and how?. Annals of Oncology, 17(9), 1347-1359. DOI: 10.1093/annonc/mdl029
- Chen, C., Edelstein, L. C., & Gélinas, C. (2000). The Rel/NF- κB family directly activates expression of the apoptosis inhibitor Bcl-xL. Molecular and cellular biology, 20(8), 2687-2695. DOI: 10.1128/MCB.20.8.2687- 2695.2000
- Chung, S.S., Wu, Y., Okobi, Q., Adekoya, D., Atefi, M., Clarke, O., ..., & Vadgama, J.V. (2017). Proinflammatory cytokines IL‐6 and TNF‐α increased telomerase activity through NF‐κB/STAT1/STAT3 activation, and withaferin a inhibited the signaling in colorectal cancer cells. Mediators of inflammation, 2017(1), 5958429. DOI: 10.1155/2017/5958429
- Çalişkan, O., & Polat, A.A. (2011). Phytochemical and antioxidant properties of selected fig (Ficus carica L.) accessions from the eastern Mediterranean region of Turkey. Scientia Horticulturae, 128(4), 473-478. DOI: 10.1016/j.scienta.2011.02.023
- Davis, P.H. (1965-1988). Flora of Turkey and the East Aegean Islands. Edinburgh: Edinburgh University Press, (Vols. I-X).
- Do, Q.D., Angkawijaya, A.E., Tran-Nguyen, P.L., Huynh, L.H., Soetaredjo, F.E., Ismadji, S., & Ju, Y.H. (2014). Effect of extraction solvent on total phenol content, total flavonoid content, and antioxidant activity of Limnophila aromatica. Journal of food and drug analysis, 22(3), 296-302. DOI: 10.1016/j.jfda.2013.11.001
- Ercisli, S., Tosun, M., Karlidag, H., Dzubur, A., Hadziabulic, S., & Aliman, Y. (2012). Color and antioxidant characteristics of some fresh fig (Ficus carica L.) genotypes from Northeastern Turkey. Plant Foods for Human Nutrition, 67(3), 271-276. DOI: 10.1007/s11130-012-0292-2