APIUM GRAVEOLENS EKSTRAKTLARININ LNCaP HÜCRELERİNDE KASPAZ-3, -8, -9 ve APAF-1 ÜZERİNE ETKİSİ
Yıl 2024,
Cilt: 25 Sayı: 3, 300 - 306, 18.07.2024
Halit Buğra Koca
,
Tülay Köken
,
Tülay Akan
Öz
AMAÇ: Bu çalışmada, prostat kanseri hücre hattı LNCaP hücrelerinde, apium graveolens (kereviz) bitkisinin etanolik ekstraktlarının hücre canlılığı ve apoptoziste rol alan kaspazlar ve apoptoz proteaz aktivasyon faktörü-1 (Apaf-1) üzerine indükleyici/baskılayıcı olarak anti-kanser etkisinin araştırılması amaçlandı.
GEREÇ VE YÖNTEM: Çalışmamızda LNCaP hücre hattı kullanıldı. LNCaP hücreleri; 0, 1500, 2000, 2500 μg/mL arasında değişen ve artan konsantrasyonlarda apium graveolens'in etanolik ekstraktları ile muamele edilen 4 gruba ayrıldı. Belirtilen ekstrakt konsantrasyonları LNCaP hücrelerine 24 ve 48 saat ayrı ayrı uygulandı. Uygulama bitiminde hazırlanan hücre lizatından ELISA yöntemiyle; Kaspaz-3, -8, -9 ve Apaf-1 ölçümü yapıldı. Sonuçlar canlı hücre sayılarıyla oranlanarak ng/ml olarak verildi.
BULGULAR: LNCaP prostat kanser hücrelerinin apium graveolens ekstraktları ile 24 ve 48 saatliğine muamelesi kaspaz-3 ve kaspaz-9 düzeylerinde anlamlı bir farklılığa neden olmadı. Bununla birlikte; 24 ve 48 saatlik uygulamada, 2000 ve 2500 μg/ml ekstrakt konsantrasyonlarında kaspaz-8 değerleri kontrol gruplarına göre ve 2500 μg/ml ekstrakt konsantrasyonunda ise Apaf-1 düzeyi kontrol gruplarına göre doza ve zamana bağımlı olarak istatistiksel bakımdan anlamlı artış gösterdi.
SONUÇ: Bu çalışmanın sonuçları, apium graveolens bitkisinin etanolik ekstraktlarının uygulandığı LNCaP prostat kanser hücre hattında kaspaz-8 ve Apaf-1 düzeylerini artırarak antikanser ve apoptotik özelliğe sahip olduğunu göstermektedir. Bulgularımızı desteklemek için daha ileri in-vitro ve in-vivo çalışmalara ihtiyaç vardır.
Destekleyen Kurum
Afyon Kocatepe Üniversitesi Bilimsel Araştırma Projeleri Koordinatörlüğü
Proje Numarası
16.KARİYER.188
Kaynakça
- 1. Wei GJ, Chao YH, Tung YC, et al. tangeretin derivative inhibits the growth of human prostate cancer LNCaP cells by epigenetically restoring p21 gene expression and inhibiting cancer stem-like cell proliferation. The AAPS Journal. 2023;25(4):59.
- 2. Sekhoacha M, Riet K, Motloung P, et al. Prostate cancer review: Genetics, diagnosis, treatment options, and
alternative approaches. Molecules. 2022;27(17):5730.
- 3. Dasari S, Samy ALPA, Narvekar P, et al. Polygodial analog induces apoptosis in LNCaP prostate cancer cells.
European Journal of Pharmacology. 2018;828:154-62.
- 4. Al Aboody MS. Cytotoxic, antioxidant, and antimicrobial activities of Celery (Apium graveolens L.).
Bioinformation. 2021;17(1):147.
- 5. Jeong SH, Kim HH, Park MY, et al. Flavones: The Apoptosis in Prostate Cancer of Three Flavones Selected as
Therapeutic Candidate Models. International Journal of Molecular Sciences. 2023;24(11):9240.
- 6. Khairullah AR, Solikhah TI, Ansori ANM, et al. Review on the Pharmacological and Health Aspects of Apium
Graveolens or Celery: An Update. Systematic Reviews in Pharmacy. 2021;12(1):606-12.
- 7. Singhal B, Pandey P, Khan F, et al. In vitro elucidation of antiproliferative and apoptotic effects of thymol
against prostate cancer LNCaP cells. Biointerface Research in Applied Chemistry. 2022;12(1):1279-89.
- 8. Köken T, Koca B, Özkurt M, et al. Apium graveolens extract inhibits cell proliferation and expression of
vascular endothelial growth factor and induces apoptosis in the human prostatic carcinoma cell line LNCaP.
Journal of Medicinal Food. 2016;19(12):1166-71.
- 9. Asati V. Perspectives of anti-cancer phytoconstituents in pharmacotherapy. Int. J. Med. Pharm. Sci.
2022;12:1.
- 10. Khan T, Ali M, Khan A, et al. Anticancer plants: A review of the active phytochemicals, applications in
animal models, and regulatory aspects. Biomolecules. 2019;10(1):47.
- 11. Zielinski RR, Eigl BJ, Chi KN. Targeting the apoptosis pathway in prostate cancer. The Cancer Journal.
2013;19(1):79-89.
- 12. Boice A, Bouchier-Hayes L. Targeting apoptotic caspases in cancer. Biochimica et Biophysica Acta (BBA)-
Molecular Cell Research. 2020;1867(6):118688.
- 13. Ahmedy O. Study of the anticancer potential of celery seed oil against chemically induced hepatocellular
carcinoma in rats: a mechanistic approach. Al-azhar Journal of Pharmaceutical Sciences. 2016;53(1):14-28.
- 14. Becit-Kizilkaya M, Oncu S, Sen S, Celik S. Berberine synergizes with cisplatin via inducing apoptosis on A549
non-small cell lung cancer cells. European Journal of Therapeutics.2023; 29(3):488-496.
- 15. Oncu S, Becit-Kizilkaya M, Sen S, Ugur-Kaplan AB, Cetin M, Celik S. Daidzein nanosuspension in
combination with cisplatin to enhance therapeutic efficacy against A549 non-small lung cancer cells: an in
vitro evaluation. Naunyn Schmiedebergs Arch Pharmacol. 2023: 38159158.
- 16. Lyngdoh A, Baruah TJ, Sharan RN, Kma L. Inhibitory Potential of Apium graveolens L. Extract on
Inflammation in Diethylnitrosamine-induced Hepatocellular Carcinoma in Mice. Pharmacognosy Magazine.
2023;09731296231170931.
- 17. Zhou M, Liu X, Li Z, et al. Caspase‐3 regulates the migration, invasion and metastasis of colon cancer cells.
- International Journal of Cancer. 2018;143(4):921-30.
- 18. Xia J, Zhang J, Wang L, et al. Non-apoptotic function of caspase-8 confers prostate cancer enzalutamide
resistance via NF-κB activation. Cell Death & Disease. 2021;12(9):833.
- 19. Gopalakrishnan S, Ismail A. Aromatic monophenols from cinnamon bark act as proteasome inhibitors by
upregulating ER stress, suppressing FoxM1 expression, and inducing apoptosis in prostate cancer cells.
Phytotherapy Research. 2021;35(10):5781-94.
- 20. Kaur P, Dhandayuthapani S, Venkatesan T, et al. Molecular mechanism of C-phycocyanin induced
apoptosis in LNCaP cells. Bioorganic & Medicinal Chemistry. 2020;28(3):115272.
- 21. Zhang K, Liu X, Samuel Ravi SOA, et al. Synthesis of silver nanoparticles (AgNPs) from leaf extract of Salvia
miltiorrhiza and its anticancer potential in human prostate cancer LNCaP cell lines. Artificial Cells,
Nanomedicine, and Biotechnology. 2019;47(1):2846-54.
- 22. Safavi M, Shakeri R, Ardestani SK, et al. Caspase-dependent apoptosis induced by two synthetic
halogenated flavanones, 3', 7-dichloroflavanone and 3', 6-dichloroflavanone, on human breast and prostate
cancer cells. In Vitro Cellular & Developmental Biology-Animal. 2018;54:136-46.
- 23. Javid H, Ahmadi S, Mohamadian E. Therapeutic applications of apigenin and its derivatives: micro and
nano aspects. Micro Nano Bio Aspects. 2023;2(1):30-8.
- 24. Yadav N, Gogada R, O'Malley J, et al. Molecular insights on cytochrome c and nucleotide regulation of
apoptosome function and its implication in cancer. Biochimica et Biophysica Acta (BBA)-Molecular Cell
Research. 2020;1867(1):118573.
- 25. Mu D, Zhou G, Li J, et al. Ursolic acid activates the apoptosis of prostate cancer via ROCK/PTEN mediated
mitochondrial translocation of cofilin-1. Oncology Letters. 2018;15(3):3202-6.
- 26. Avrutsky MI, Troy CM. Caspase-9: a multimodal therapeutic target with diverse cellular expression in
human disease. Frontiers in Pharmacology. 2021;12:701301.
EFFECT OF APIUM GRAVEOLENS EXTRACTS ON CASPASE-3, -8, -9 AND APAF-1 IN LNCaP CELLS
Yıl 2024,
Cilt: 25 Sayı: 3, 300 - 306, 18.07.2024
Halit Buğra Koca
,
Tülay Köken
,
Tülay Akan
Öz
OBJECTIVE: In this study it was aimed to investigate the anti-cancer effect of ethanolic extracts of apium graveolens (celery) plant on cell viability, caspases involved in apoptosis and apoptosis protease activation factor-1 (Apaf-1) as inducer/suppressor in prostate cancer cell line LNCaP cells.
MATERIAL AND METHODS: LNCaP cell line was used in our study. LNCaP cells were divided into 4 groups treated with ethanolic extracts of apium graveolens at increasing concentrations ranging from 0, 1500, 2000, 2500 μg/mL. The indicated extract concentrations were applied to LNCaP cells separately for 24 and 48 hours. Caspase-3, -8, -9 and Apaf-1 were measured by ELISA method from the cell lysate prepared at the end of the treatment. The results were expressed as ng/ml in proportion to the number of viable cells.
RESULTS: Treatment of LNCaP prostate cancer cells with apium graveolens extracts for 24 and 48 hours did not cause a significant difference in caspase-3 and caspase-9 levels. However, caspase-8 levels were significantly increased at 2000 and 2500 μg/ml extract concentrations and Apaf-1 levels were significantly increased at 2500 μg/ml extract concentration in a dose- and time-dependent manner compared to the control groups at 24 and 48 hours.
CONCLUSIONS: The results of this study show that ethanolic extracts of apium graveolens plant have anticancer and apoptotic properties by increasing caspase-8 and Apaf-1 levels in LNCaP prostate cancer cell line. Further in-vitro and in-vivo studies are needed to support our findings.
Proje Numarası
16.KARİYER.188
Kaynakça
- 1. Wei GJ, Chao YH, Tung YC, et al. tangeretin derivative inhibits the growth of human prostate cancer LNCaP cells by epigenetically restoring p21 gene expression and inhibiting cancer stem-like cell proliferation. The AAPS Journal. 2023;25(4):59.
- 2. Sekhoacha M, Riet K, Motloung P, et al. Prostate cancer review: Genetics, diagnosis, treatment options, and
alternative approaches. Molecules. 2022;27(17):5730.
- 3. Dasari S, Samy ALPA, Narvekar P, et al. Polygodial analog induces apoptosis in LNCaP prostate cancer cells.
European Journal of Pharmacology. 2018;828:154-62.
- 4. Al Aboody MS. Cytotoxic, antioxidant, and antimicrobial activities of Celery (Apium graveolens L.).
Bioinformation. 2021;17(1):147.
- 5. Jeong SH, Kim HH, Park MY, et al. Flavones: The Apoptosis in Prostate Cancer of Three Flavones Selected as
Therapeutic Candidate Models. International Journal of Molecular Sciences. 2023;24(11):9240.
- 6. Khairullah AR, Solikhah TI, Ansori ANM, et al. Review on the Pharmacological and Health Aspects of Apium
Graveolens or Celery: An Update. Systematic Reviews in Pharmacy. 2021;12(1):606-12.
- 7. Singhal B, Pandey P, Khan F, et al. In vitro elucidation of antiproliferative and apoptotic effects of thymol
against prostate cancer LNCaP cells. Biointerface Research in Applied Chemistry. 2022;12(1):1279-89.
- 8. Köken T, Koca B, Özkurt M, et al. Apium graveolens extract inhibits cell proliferation and expression of
vascular endothelial growth factor and induces apoptosis in the human prostatic carcinoma cell line LNCaP.
Journal of Medicinal Food. 2016;19(12):1166-71.
- 9. Asati V. Perspectives of anti-cancer phytoconstituents in pharmacotherapy. Int. J. Med. Pharm. Sci.
2022;12:1.
- 10. Khan T, Ali M, Khan A, et al. Anticancer plants: A review of the active phytochemicals, applications in
animal models, and regulatory aspects. Biomolecules. 2019;10(1):47.
- 11. Zielinski RR, Eigl BJ, Chi KN. Targeting the apoptosis pathway in prostate cancer. The Cancer Journal.
2013;19(1):79-89.
- 12. Boice A, Bouchier-Hayes L. Targeting apoptotic caspases in cancer. Biochimica et Biophysica Acta (BBA)-
Molecular Cell Research. 2020;1867(6):118688.
- 13. Ahmedy O. Study of the anticancer potential of celery seed oil against chemically induced hepatocellular
carcinoma in rats: a mechanistic approach. Al-azhar Journal of Pharmaceutical Sciences. 2016;53(1):14-28.
- 14. Becit-Kizilkaya M, Oncu S, Sen S, Celik S. Berberine synergizes with cisplatin via inducing apoptosis on A549
non-small cell lung cancer cells. European Journal of Therapeutics.2023; 29(3):488-496.
- 15. Oncu S, Becit-Kizilkaya M, Sen S, Ugur-Kaplan AB, Cetin M, Celik S. Daidzein nanosuspension in
combination with cisplatin to enhance therapeutic efficacy against A549 non-small lung cancer cells: an in
vitro evaluation. Naunyn Schmiedebergs Arch Pharmacol. 2023: 38159158.
- 16. Lyngdoh A, Baruah TJ, Sharan RN, Kma L. Inhibitory Potential of Apium graveolens L. Extract on
Inflammation in Diethylnitrosamine-induced Hepatocellular Carcinoma in Mice. Pharmacognosy Magazine.
2023;09731296231170931.
- 17. Zhou M, Liu X, Li Z, et al. Caspase‐3 regulates the migration, invasion and metastasis of colon cancer cells.
- International Journal of Cancer. 2018;143(4):921-30.
- 18. Xia J, Zhang J, Wang L, et al. Non-apoptotic function of caspase-8 confers prostate cancer enzalutamide
resistance via NF-κB activation. Cell Death & Disease. 2021;12(9):833.
- 19. Gopalakrishnan S, Ismail A. Aromatic monophenols from cinnamon bark act as proteasome inhibitors by
upregulating ER stress, suppressing FoxM1 expression, and inducing apoptosis in prostate cancer cells.
Phytotherapy Research. 2021;35(10):5781-94.
- 20. Kaur P, Dhandayuthapani S, Venkatesan T, et al. Molecular mechanism of C-phycocyanin induced
apoptosis in LNCaP cells. Bioorganic & Medicinal Chemistry. 2020;28(3):115272.
- 21. Zhang K, Liu X, Samuel Ravi SOA, et al. Synthesis of silver nanoparticles (AgNPs) from leaf extract of Salvia
miltiorrhiza and its anticancer potential in human prostate cancer LNCaP cell lines. Artificial Cells,
Nanomedicine, and Biotechnology. 2019;47(1):2846-54.
- 22. Safavi M, Shakeri R, Ardestani SK, et al. Caspase-dependent apoptosis induced by two synthetic
halogenated flavanones, 3', 7-dichloroflavanone and 3', 6-dichloroflavanone, on human breast and prostate
cancer cells. In Vitro Cellular & Developmental Biology-Animal. 2018;54:136-46.
- 23. Javid H, Ahmadi S, Mohamadian E. Therapeutic applications of apigenin and its derivatives: micro and
nano aspects. Micro Nano Bio Aspects. 2023;2(1):30-8.
- 24. Yadav N, Gogada R, O'Malley J, et al. Molecular insights on cytochrome c and nucleotide regulation of
apoptosome function and its implication in cancer. Biochimica et Biophysica Acta (BBA)-Molecular Cell
Research. 2020;1867(1):118573.
- 25. Mu D, Zhou G, Li J, et al. Ursolic acid activates the apoptosis of prostate cancer via ROCK/PTEN mediated
mitochondrial translocation of cofilin-1. Oncology Letters. 2018;15(3):3202-6.
- 26. Avrutsky MI, Troy CM. Caspase-9: a multimodal therapeutic target with diverse cellular expression in
human disease. Frontiers in Pharmacology. 2021;12:701301.