İNCİR ÇEKİRDEĞİ YAĞININ KOLOREKTAL KANSER HÜCRE HATLARI ÜZERİNDEKİ SİTOTOKSİK VE ANTİ-İNVAZİV ETKİLERİ

Öz

Amaç: Kolorektal kanser (KRC), dünya genelinde yüksek morbidite ve mortaliteye sahip yaygın bir malignitedir. Cerrahi ve kemoterapi gibi geleneksel tedavilerin yanında, doğal kaynaklı biyoaktif bileşiklerin destekleyici terapötik potansiyelleri üzerine çalışmalar giderek artmaktadır. Bu çalışma, incir (Ficus carica) çekirdeği yağının HT-29 ve DLD-1 kolorektal kanser hücre hatlarında proliferasyon ve invazyon üzerindeki etkilerinin in vitro koşullarda değerlendirilmesini amaçlamaktadır. Gereç ve Yöntem: İncir çekirdeği yağının kimyasal bileşimi GC-FID ve HPLC analizleri ile karakterize edilmiştir. Sitotoksik etkiler Alamar Blue testi ile değerlendirilmiş ve IC₅₀ değerleri hesaplanmıştır; invazyon kapasitesi ise Matrigel transwell invazyon analizi ile belirlenmiştir. Sonuç ve Tartışma: Analiz sonuçlarına göre, incir çekirdeği yağı yüksek düzeyde α-linolenik asit (%39.97), linoleik asit (%33.24), oleik asit (%16.71) ve γ-tokoferol (4800 mg/kg) içermektedir. Yağ, HT-29 ve DLD-1 hücrelerinde doza bağlı antiproliferatif etki göstermiş, sağlıklı PNT1A hücrelerinde ise daha düşük toksisite sergilemiştir. Ayrıca, her iki kanser hücre hattında anlamlı düzeyde invazyon inhibisyonu saptanmıştır. Bulgular, incir çekirdeği yağının antikanser potansiyel taşıyan doğal bir ajan olabileceğini göstermektedir.

Anahtar Kelimeler

• İncir çekirdeği yağı
• invazyon
• kolorektal kanser
• sitotoksisite
• γ-tokoferol

EFFECTS OF FIG SEED OIL ON THE PROLIFERATION AND INVASION OF COLORECTAL CANCER CELL LINES

Öz

Objective: Colorectal cancer (CRC) is a common malignancy associated with high morbidity and mortality worldwide. In addition to conventional treatments such as surgery and chemotherapy, there is a growing interest in the therapeutic potential of naturally derived bioactive compounds. This study aims to evaluate the in vitro effects of fig (Ficus carica) seed oil on the proliferation and invasion of HT-29 and DLD-1 colorectal cancer cell lines. Material and Method: The chemical composition of fig seed oil was characterized by GC-FID and HPLC analyses. Cytotoxic effects were assessed using the Alamar Blue assay, and IC₅₀ values were calculated. Invasion capacity was determined through a Matrigel-transwell invasion assay. Result and Discussion: According to the analysis results, fig seed oil was found to be rich in α-linolenic acid (39.97%), linoleic acid (33.24%), oleic acid (16.71%), and γ-tocopherol (4800 mg/kg). The oil exhibited dose-dependent antiproliferative activity on HT-29 and DLD-1 cells, while demonstrating lower toxicity on healthy PNT1A cells. Furthermore, a significant inhibition of invasion was observed in both cancer cell lines. These findings suggest that fig seed oil may serve as a natural agent with anticancer potential for use in CRC management.

Anahtar Kelimeler

• Colorectal cancer
• cytotoxicity
• fig seed oil
• invasion
• γ-tocopherol

Kaynakça

1. 1. Wild, C.P., Weiderpass, E., Stewart, B.W., editors (2020). World Cancer Report: Cancer Research for Cancer Prevention. Lyon, France: International Agency for Research on Cancer. Available from: https://publications.iarc.fr/586. Licence: CC BY-NC-ND 3.0 IGO.
2. 2. T.C. Sağlık Bakanlığı Halk Sağlığı Genel Müdürlüğü. (2022). 2020 yılı Türkiye kanser istatistikleri. https://hsgm.saglik.gov.tr/tr/kanser-istatistikleri.
3. 3. Mármol, I., Sánchez-de-Diego, C., Pradilla Dieste, A., Cerrada, E., Rodriguez Yoldi, M.J. (2017). Colorectal carcinoma: A general overview and future perspectives in colorectal cancer. International Journal of Molecular Sciences, 18(1), 197. [CrossRef]
4. 4. Willett, W.C. (2005). Diet and cancer: An evolving picture. JAMA, 293, 233-234. [CrossRef]
5. 5. Keum, N., Giovannucci, E. (2019). Global burden of colorectal cancer: Emerging trends, risk factors and prevention strategies. Nature Reviews Gastroenterology & Hepatology, 16, 713-732. [CrossRef]
6. 6. Huang, X.M., Yang, Z.J., Xie, Q., Zhang, Z.K., Zhang, H., Ma, J.Y. (2019). Natural products for treating colorectal cancer: A mechanistic review. Biomedicine & Pharmacotherapy, 117, 109142. [CrossRef]
7. 7. Hossain, M.S., Urbi, Z., Sule, A., Rahman, K.M.H. (2014). Andrographis paniculata (Burm. f.) Wall. ex Nees: A review of ethnobotany, phytochemistry, and pharmacology. Scientific World Journal, 2014, 274905. [CrossRef]
8. 8. Hossain, M.S., Urbi, Z., Phang, I.C. (2021). Auxin increased adventitious root development in the medicinal plant Andrographis paniculata (Burm. f.) Wall. ex Nees. Agronomy Journal, 113, 3222-3231. [CrossRef]

9. 9. Sumara, A., Stachniuk, A., Montowska, M., Kotecka-Majchrzak, K., Grywalska, E., Mitura, P., Martinović, L., Pavelić, S., Fornal, E. (2022). Comprehensive review of seven plant seed oils: Chemical composition, nutritional properties, and biomedical functions. Food Reviews International, 39, 5402-5422. [CrossRef]
10. 10. Kaseke, T., Opara, U., Fawole, O. (2020). Fatty acid composition, bioactive phytochemicals, antioxidant properties and oxidative stability of edible fruit seed oil: Effect of preharvest and processing factors. Heliyon, 6, e04962. [CrossRef]
11. 11. Rahim, M., Shoukat, A., Khalid, W., Ejaz, A., Itrat, N., Majeed, I., Koraqi, H., Imran, M., Nisa, M., Nazir, A., Alansari, W., Eskandrani, A., Shamlan, G., Al-Farga, A. (2022). A narrative review on various oil extraction methods, encapsulation processes, fatty acid profiles, oxidative stability, and medicinal properties of black seed (Nigella sativa). Foods, 11. [CrossRef]
12. 12. Rahim, M.A., Shoukat, A., Khalid, W., Ejaz, A., Itrat, N., Majeed, I., Koraqi, H., Imran, M., Nisa, M.U., Nazir, A., Alansari, W.S., Eskandrani, A.A., Shamlan, G., Al-Farga, A. (2022). A narrative review on various oil extraction methods, encapsulation processes, fatty acid profiles, oxidative stability, and medicinal properties of black seed (Nigella sativa). Foods, 11(18), 2826. [CrossRef]
13. 13. Matthäus, B., Özcan, M.M. (2011). Fatty acids, tocopherol, and sterol contents of some Nigella species seed oil. Czech Journal of Food Sciences, 29(2), 145-150. [CrossRef]
14. 14. Xie, Y., Yan, Z., Niu, Z., Coulter, J. A., Niu, J., Zhang, J., Wang, B., Yan, B., Zhao, W., Wang, L. (2020). Yield, oil content, and fatty acid profile of flax (Linum usitatissimum L.) as affected by phosphorus rate and seeding rate. Industrial Crops and Products, 145, 112087. [CrossRef]
15. 15. Dąbrowski, G., Czaplicki, S., & Konopka, I. (2019). Fractionation of sterols, tocols and squalene in flaxseed oils under the impact of variable conditions of supercritical CO₂ extraction. Journal of Food Composition and Analysis, 83, 103261. [CrossRef]
16. 16. Mujtaba, M.A., Cho, H.M., Masjuki, H.H., Kalam, M.A., Ong, H.C., Gul, M., Harith, M.H., Yusoff, M.N.A.M. (2020). Critical review on sesame seed oil and its methyl ester on cold flow and oxidation stability. Energy Reports, 6, 40-54. [CrossRef]
17. 17. Rangkadilok, N., Pholphana, N., Mahidol, C., Wongyai, W., Saengsooksree, K., Nookabkaew, S., Satayavivad, J. (2010). Variation of sesamin, sesamolin and tocopherols in sesame (Sesamum indicum L.) seeds and oil products in Thailand. Food Chemistry, 122(3), 724-730. [CrossRef]
18. 18. Vardin, Y., Şirinyıldız, D., Yorulmaz, A. (2023). Impact of roasting on quality and compositional characteristics of fig seed oil. Tarım Bilimleri Dergisi, 29(2), 404-412. [CrossRef]
19. 19. Ustun-Argon, Z., Sarı, Z., Gokyer, A., Buyukhelvacigil-Ozturk, S. (2021). Phytochemical evaluation of Ficus carica seeds and their cold pressed oil. Journal of Pharmaceutical Research, 20(4), 71-79. [CrossRef]
20. 20. Şirinyıldız, D., Vardin, Y., Yorulmaz, A. (2023). The influence of microwave roasting on bioactive components and chemical parameters of cold pressed fig seed oil. Grasas y Aceites, 74(1). [CrossRef]
21. 21. Mert, H., Mert, N., Cibuk, S., Yildirim, S., Mert, N. (2024). Antidiabetic effect of fig seed oil in rats with diabetes induced by streptozotocin. Journal of Oleo Science, 73(5), 717-727. [CrossRef]
22. 22. Matsunaga, W., Gotoh, A. (2023). Cancer cell-specific gene disruption of VEGF-A using Cas9. Personalized Medicine Universe, 12, 8-15. [CrossRef]
23. 23. Karakurt, S., Adali, O. (2016). Tannic acid inhibits proliferation, migration, invasion of prostate cancer and modulates drug metabolizing and antioxidant enzymes. Anti-Cancer Agents in Medicinal Chemistry, 16(6), 781-789. [CrossRef]
24. 24. Tarlacı, S. (2021). A new source of omega-3 and gamma tocopherol: Fig (Ficus carica L.) seed oil. Harran Tarım ve Gıda Bilimleri Dergisi, 25(4), 556-560. [CrossRef]
25. 25. Soltana, H., Tekaya, M., Amri, Z., El-Gharbi, S., Nakbi, A., Harzallah, A., Hammami, M. (2016). Characterization of fig achenes’ oil of Ficus carica grown in Tunisia. Food Chemistry, 196, 1125-1130. [CrossRef]
26. 26. Ivanov, D.S., Lević, J.D., Sredanović, S.A. (2010). Fatty acid composition of various soybean products. Food and Feed Research, 37(2), 65-70.
27. 27. Rodrigues, A.C., Ströher, G.L., Freitas, A.R., Visentainer, J.V., Oliveira, C.C., De Souza, N.E. (2011). The effect of genotype and roasting on the fatty acid composition of peanuts. Food Research International, 44(1), 187-192. [CrossRef]
28. 28. Sun, Q., Shi, J., Scanlon, M., Xue, S.J., Lu, J. (2021). Optimization of supercritical-CO2 process for extraction of tocopherol-rich oil from canola seeds. Lwt, 145, 111435. [CrossRef]
29. 29. Ghosh, S., Zhang, S., Azam, M., Gebregziabher, B.S., Abdelghany, A.M., Shaibu, A.S., Qi, J., Feng, Y., Agyenim-Boateng, K.G., Liu, Y., Feng, H., Li, Y., Li, J., Li, B., Sun, J. (2022). Natural variation of seed tocopherol composition in diverse world soybean accessions from maturity group 0 to VI grown in China. Plants, 11(2), 206. [CrossRef]
30. 30. Ouchikh, O., Chahed, T., Ksouri, R., Taarit, M. B., Faleh, H., Abdelly, C., Kchouk, M.E., Marzouk, B. (2011). The effects of extraction method on the measured tocopherol level and antioxidant activity of L. nobilis vegetative organs. Journal of Food Composition and Analysis, 24(1), 103-110. [CrossRef]
31. 31. Pahrudin Arrozi, A., Shukri, S.N.S., Wan Ngah, W.Z., Mohd Yusof, Y.A., Ahmad Damanhuri, M.H., Jaafar, F., Makpol, S. (2020). Comparative effects of alpha- and gamma-tocopherol on mitochondrial functions in Alzheimer’s disease in vitro model. Scientific Reports, 10, 8962. [CrossRef]
32. 32. Konda, A., Nazarenus, T., Nguyen, H., Yang, J., Gelli, M., Swenson, S., Shipp, J., Schmidt, M., Cahoon, R., Çiftçi, O., Zhang, C., Clemente, T., Cahoon, E. (2019). Metabolic engineering of soybean seeds for enhanced vitamin E tocochromanol content and effects on oil antioxidant properties in polyunsaturated fatty acid-rich germplasm. Metabolic Engineering. [CrossRef]
33. 33. Al-Hwaiti, M., Alsbou, E., Sheikha, A., Bakchiche, B., Pham, T., Thomas, R., Bardaweel, S. (2020). Evaluation of the anticancer activity and fatty acids composition of “Handal” (Citrullus colocynthis L.) seed oil, a desert plant from south Jordan. Food Science & Nutrition, 9, 282-289. [CrossRef]
34. 34. Jang, Y., Park, N.Y., Rostgaard-Hansen, A.L., Huang, J., Jiang, Q. (2016). Vitamin E metabolite 13’-carboxychromanols inhibit pro-inflammatory enzymes, induce apoptosis and autophagy in human cancer cells by modulating sphingolipids and suppress colon tumor development in mice. Free Radical Biology and Medicine, 95, 190–199. [CrossRef]
35. 35. Rincón-Cervera, M., Valenzuela, R., Hernández-Rodas, M., Barrera, C., Espinosa, A., Marambio, M., Valenzuela, A. (2016). Vegetable oils rich in alpha linolenic acid increment hepatic n-3 LCPUFA, modulating the fatty acid metabolism and antioxidant response in rats. Prostaglandins, Leukotrienes, and Essential Fatty Acids, 111, 25-35. [CrossRef]
36. 36. Srivastava, D., Singh, V., Kumar, U., R., V. (2021). Alpha-linolenic acid: A pharmacologically active ingredient from nature. The Indian Journal of Nutrition and Dietetics. [CrossRef]
37. 37. Vara-Messler, M., Pasqualini, M., Comba, A., Silva, R., Buccellati, C., Trenti, A., Trevisi, L., Eynard, A., Sala, A., Bolego, C., Valentich, M. (2017). Increased dietary levels of α-linoleic acid inhibit mammary tumor growth and metastasis. European Journal of Nutrition, 56, 509-519. [CrossRef]
38. 38. Alan, N., Oran, N.T., Yılmaz, P.A., Çelik, A., Yılmaz, O. (2024). Fig seed oil improves intestinal damage caused by 5‐FU‐induced mucositis in rats. Food Science & Nutrition, 12(9), 6461-6471.[CrossRef]
39. 39. Dawaba, A.M., Dawaba, H.M. (2019). Application of optimization technique to develop nano-based carrier of Nigella sativa essential oil: Characterization and assessment. Recent Patents on Drug Delivery & Formulation, 13(3), 228-240. [CrossRef]
40. 40. Ni, C., Li, B., Ding, Y., Wu, Y., Wang, Q., Wang, J., Cheng, J. (2021). Anti-cancer properties of coix seed oil against HT-29 colon cells through regulation of the PI3K/AKT signaling pathway. Foods, 10(11), 2833. [CrossRef]
41. 41. Gębarowski, T., Wiatrak, B., Jęśkowiak-Kossakowska, I., Grajzer, M., Prescha, A. (2023). Oils from transgenic flax lines as potential chemopreventive agents in colorectal cancer. Biomedicines, 11(9), 2592. [CrossRef]
42. 42. Gill, C. I., Boyd, A., McDermott, E., McCann, M., Servili, M., Selvaggini, R., Taticchi, A., Esposto, S., Montedoro, G., McGlynn, H., Rowland, I. (2005). Potential anti‐cancer effects of virgin olive oil phenols on colorectal carcinogenesis models in vitro. International Journal of Cancer, 117(1), 1-7. [CrossRef]
43. 43. González-Fernández, M.J., Ortea, I., Guil-Guerrero, J.L. (2020). α-Linolenic and γ-linolenic acids exercise differential antitumor effects on HT-29 human colorectal cancer cells. Toxicology Research, 9(4), 474-483. [CrossRef]
44. 44. Yan, H., Zhang, S., Yang, L., Jiang, M., Xin, Y., Liao, X., Li, Y., Lu, J. (2024). The antitumor effects of α-linolenic acid. Journal of Personalized Medicine, 14(3), 260. [CrossRef]
45. 45. Su, C.C., Yu, C.C., Shih, Y.W., Liu, K.L., Chen, H.W., Wu, C.C., Yang, Y.C., Yeh, E.L., Li, C. C. (2023). Effect of alpha-linolenic acid on human oral squamous cell carcinoma metastasis and apoptotic cell death. Biomedicine & Pharmacotherapy, 161, 114393. [CrossRef]
46. 46. Campbell, S., Stone, W., Whaley, S., Krishnan, K. (2003). Development of gamma (γ)-tocopherol as a colorectal cancer chemopreventive agent. Critical Reviews in Oncology/Hematology, 47(3), 249-259. [CrossRef]
47. 47. Jiang, Q., Elson-Schwab, I., Courtemanche, C., Ames, B.N. (2000). γ-Tocopherol and its major metabolite, in contrast to α-tocopherol, inhibit cyclooxygenase activity in macrophages and epithelial cells. Proceedings of the National Academy of Sciences, 97(21), 11494-11499. [CrossRef]