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Empagliflozinin Caco-2, LNCaP ve A2780 insan kanser hücre hatlarında sitotoksik etkilerinin incelenmesi

Yıl 2026, Cilt: 7 Sayı: 1, 1 - 8, 31.01.2026
https://doi.org/10.47482/acmr.1663941

Öz

Giriş: Kanser, yüksek morbidite ve mortalite oranlarıyla önemli bir sağlık sorunu olup, yeni tedavi stratejileri gerektirmektedir. Kemoterapinin etkinliğine rağmen, ilaç direnci ve yan etkiler önemli zorluklar yaratmaktadır. Son yıllarda, ilaç yeniden konumlandırma yaklaşımı yeni tedavi seçenekleri için umut verici bir strateji olarak öne çıkmıştır. Diyabet tedavisi için geliştirilen SGLT2 inhibitörleri, potansiyel antikanserojenik etkileriyle dikkat çekmektedir. Bu çalışmada, empagliflozinin CaCo-2, A2780 ve LNCaP hücre hatlarındaki sitotoksik etkileri incelenmiştir
Materyal Metot: Bu çalışmada A2780, LNCaP ve Caco-2 hücre hatları kullanılmıştır. Tüm hücre hatları, 1, 5, 25, 50 ve 100 μM konsantrasyonlarında empagliflozin ile 48 saat boyunca muamele edilmiştir. Hücre canlılığındaki değişimler MTT testi ile belirlenmiştir. Sitotoksisite sonuçlarına dayanarak, empagliflozinin yarı maksimum inhibitör konsantrasyonu (IC50) ve logIC50 değerleri hesaplanmıştır.
Bulgular: Empagliflozin CaCo-2, A2780 ve LNCaP hücre hatlarında hücre canlılığını anlamlı düzeyde azaltmıştır. En belirgin sitotoksik etki LNCaP hücrelerinde gözlenirken, bunu sırasıyla CaCo-2 ve A2780 hücre hatları takip etmiştir.
Sonuç: Elde edilen bulgular, Empagliflozin’in belirli kanser hücre hatlarında sitotoksik etkiler gösterdiğini ve potansiyel bir antikanser ajan olabileceğini düşündürmektedir

Kaynakça

  • Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209-49.
  • Garg P, Malhotra J, Kulkarni P, Horne D, Salgia R, Singhal SS. Emerging Therapeutic Strategies to Overcome Drug Resistance in Cancer Cells. Cancers (Basel). 2024;16(13).
  • Xia Y, Sun M, Huang H, Jin W‑L. Drug repurposing for cancer therapy. Signal Transduct Target Ther. 2024;9(1):92.
  • Low ZY, Farouk IA, Lal SK. Drug repositioning: new approaches and future prospects for life-debilitating diseases and the COVID‑19 pandemic outbreak. Viruses. 2020;12(9):1058.
  • Al Khzem AH, Gomaa MS, Alturki MS, Tawfeeq N, Sarafroz M, Alonaizi SM, et al. Drug repurposing for cancer treatment: A comprehensive review. Int J Mol Sci. 2024;25(22):12441.
  • Dabour MS, George MY, Daniel MR, Blaes AH, Zordoky BN. The cardioprotective and anticancer effects of SGLT2 inhibitors. Cardio Oncology. 2024;6(2):159-82.
  • Heise T, Seewaldt‑Becker E, Macha S, Hantel S, Pinnetti S, Seman L, et al. Safety, tolerability, pharmacokinetics and pharmacodynamics following 4 weeks’ treatment with empagliflozin in type 2 diabetes. Diabetes Obes Metab. 2013;15(7):613‑21.
  • Santulli G, Varzideh F, Forzano I, Wilson S, Salemme L, de Donato A, et al. Functional and Clinical Importance of SGLT2‑inhibitors in Frailty. Hypertension. 2023;80(9):1800‑09.
  • Gallo LA, Wright EM, Vallon V. Probing SGLT2 as a therapeutic target for diabetes. Diabetes Vasc Dis Res. 2015;12(2):78‑89.
  • Scafoglio C, Hirayama BA, Kepe V, Liu J, Ghezzi C, Satyamurthy N, et al. Functional expression of sodium‑glucose transporters in cancer. Proc Natl Acad Sci USA. 2015;112(30):E4111‑E19.
  • Kaji K, Nishimura N, Seki K, Sato S, Saikawa S, Nakanishi K, et al. Canagliflozin attenuates liver cancer cell growth by inhibiting glucose uptake. Int J Cancer. 2018;142(8):1712‑22.
  • Faridi U, Al‑Mutairi F, Parveen H, Khateeb S. In‑vitro and in‑silico anticancer study of glimepiride and empagliflozin. Int J Life Sci Pharma Res. 2020;10:52‑57.
  • Xie Z, Wang F, Lin L, Duan S, Liu X, Li X, et al. An SGLT2 inhibitor modulates SHH expression via AMPK in cervical carcinoma cells. Cancer Lett. 2020;495:200-10.
  • Doğan H, Bahar MR, Çalışkan E, Tekin S, Uslu H, Akman F, et al. Cyclotriphosphazenes: synthesis, cytotoxic activity and docking studies. J Biomol Struct Dyn. 2022;40(7):3258‑72.
  • Korkmaz E, Tekin S. Cytotoxicity of myrtenal on human cancer cell lines. Ann Med Res. 2024;31(5):404‑8.
  • Sekerci G, Beytur L, Yuksel F, Tekin S. Anticancer effects of Meteorin‑like protein on human cancer cells. Ann Med Res. 2024;31(7):560‑4.
  • Beytur A, Tekin Ç, Çalışkan E, Tekin S, Koran K, Orhan Görgülü A, et al. Cyclotriphosphazene derivatives with hetero‑ring chalcones: cytotoxicity and DNA damage. Bioorg Chem. 2022;127:105997.
  • Oz S, Sekerci G, Yuksel F, Tekin S. Cytotoxic and genotoxic effects of nateglinide on various cancer cells. Ann Med Res. 2023;30(4):508‑12.
  • Karataş MO, Tekin S, Alici B, Sandal S. Cytotoxic effects of coumarin‑substituted benzimidazolium salts. J Chem Sci. 2019;131:1‑12.
  • Giovannucci E, Harlan DM, Archer MC, Bergenstal RM, Gapstur SM, Habel LA, et al. Diabetes and cancer: consensus report. Diabetes Care. 2010;33(7):1674‑85.
  • Bowers LW, Rossi EL, O’Flanagan CH, deGraffenried LA, Hursting SD. Insulin/IGF system in cancer. Front Endocrinol. 2015;6:77.
  • Vella V, Lappano R, Bonavita E, Maggiolini M, Clarke RB, Belfiore A, et al. Insulin/IGF axis and RAGE in cancer therapy. Endocr Rev. 2023;44(4):693‑723.
  • Zhao H, Wu K. Hyperglycemia in colorectal cancer prognosis. Am J Transl Res. 2024;16(5):2070‑81.
  • Seidu S, Alabraba V, Davies S, Newland‑Jones P, Fernando K, Bain SC, et al. SGLT2 inhibitors: new standard of care. Diabetes Ther. 2024;15(5):1099‑124.
  • Dutka M, Bobiński R, Francuz T, Garczorz W, Zimmer K, Ilczak T, et al. SGLT‑2 inhibitors in cancer treatment. Cancers (Basel). 2022;14(23).
  • Wright EM. SGLT2 and cancer. Pflugers Arch. 2020;472(9):1407‑14.
  • Shoda K, Tsuji S, Nakamura S, Egashira Y, Enomoto Y, Nakayama N, et al. Canagliflozin inhibits glioblastoma via AMPK. Cell Mol Neurobiol. 2023;43(2):879‑92.
  • Eliaa SG, Al‑Karmalawy AA, Saleh RM, Elshal MF. Empagliflozin + doxorubicin synergy in TNBC. ACS Pharmacol Transl Sci. 2020;3(6):1330‑38.
  • Bardaweel S, Issa A. SGLT transporters as cancer targets. J Pharm Pharm Sci. 2022;25:253‑65.
  • Wu W, Wang Y, Xie J, Fan S. Empagliflozin as anticancer drug. Discov Oncol. 2023;14(1):127.
  • Pandey A, Alcaraz Jr M, Saggese P, Soto A, Gomez E, Jaldu S, et al. SGLT2 inhibitors in cancer. Cancers. 2025;17(3):466.
  • Chiang CH, Chiang CH, Hsia Y, See XY, Wang S‑S, Chen Y‑J, et al. SGLT2 inhibitors in colorectal adenocarcinoma outcomes. ASCO; 2023.
  • Lai B, Xiao Y, Pu H, Cao Q, Jing H, Liu X. SGLT1 overexpression and prognosis in ovarian carcinoma. Arch Gynecol Obstet. 2012;285(5):1455‑61.

Investigation of Cytotoxic Effects of Empagliflozin on Caco-2, LNCaP and A2780 Human Cancer Cell Lines

Yıl 2026, Cilt: 7 Sayı: 1, 1 - 8, 31.01.2026
https://doi.org/10.47482/acmr.1663941

Öz

Background: Cancer is a major health concern with high morbidity and mortality rates, necessitating new treatment strategies. Despite the effectiveness of chemotherapy, drug resistance and side effects pose significant challenges. In recent years, the drug repurposing approach has emerged as a promising strategy for new therapeutic options. SGLT2 inhibitors, originally developed for diabetes treatment, have gained attention for their potential anticancer effects. In this study, the cytotoxic effects of empagliflozin on Caco-2 (colorectal adenocarcinoma), A2780 (ovarian carcinoma), and LNCaP (prostate adenocarcinoma) cell lines were investigated.
Methods: In this study, the A2780, LNCaP, and Caco-2 cell lines were utilized. Each cell line was exposed to empagliflozin at varying concentrations of 1, 5, 25, 50, and 100 μM for a duration of 48 hours. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was employed to evaluate changes in cell viability following treatment. From the cytotoxicity data, the half-maximal inhibitory concentration (IC50) and logIC50 values of empagliflozin were determined to assess its inhibitory effects on cell viability.
Results: Empagliflozin significantly reduced cell viability in Caco-2, A2780, and LNCaP cell lines. The most pronounced cytotoxic effect was observed in LNCaP cells, followed by Caco-2 and A2780 cell lines, respectively.
Conclusion: These findings suggest that Empagliflozin exhibits cytotoxic effects in certain cancer cell lines and may have potential as an anticancer agent.

Kaynakça

  • Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209-49.
  • Garg P, Malhotra J, Kulkarni P, Horne D, Salgia R, Singhal SS. Emerging Therapeutic Strategies to Overcome Drug Resistance in Cancer Cells. Cancers (Basel). 2024;16(13).
  • Xia Y, Sun M, Huang H, Jin W‑L. Drug repurposing for cancer therapy. Signal Transduct Target Ther. 2024;9(1):92.
  • Low ZY, Farouk IA, Lal SK. Drug repositioning: new approaches and future prospects for life-debilitating diseases and the COVID‑19 pandemic outbreak. Viruses. 2020;12(9):1058.
  • Al Khzem AH, Gomaa MS, Alturki MS, Tawfeeq N, Sarafroz M, Alonaizi SM, et al. Drug repurposing for cancer treatment: A comprehensive review. Int J Mol Sci. 2024;25(22):12441.
  • Dabour MS, George MY, Daniel MR, Blaes AH, Zordoky BN. The cardioprotective and anticancer effects of SGLT2 inhibitors. Cardio Oncology. 2024;6(2):159-82.
  • Heise T, Seewaldt‑Becker E, Macha S, Hantel S, Pinnetti S, Seman L, et al. Safety, tolerability, pharmacokinetics and pharmacodynamics following 4 weeks’ treatment with empagliflozin in type 2 diabetes. Diabetes Obes Metab. 2013;15(7):613‑21.
  • Santulli G, Varzideh F, Forzano I, Wilson S, Salemme L, de Donato A, et al. Functional and Clinical Importance of SGLT2‑inhibitors in Frailty. Hypertension. 2023;80(9):1800‑09.
  • Gallo LA, Wright EM, Vallon V. Probing SGLT2 as a therapeutic target for diabetes. Diabetes Vasc Dis Res. 2015;12(2):78‑89.
  • Scafoglio C, Hirayama BA, Kepe V, Liu J, Ghezzi C, Satyamurthy N, et al. Functional expression of sodium‑glucose transporters in cancer. Proc Natl Acad Sci USA. 2015;112(30):E4111‑E19.
  • Kaji K, Nishimura N, Seki K, Sato S, Saikawa S, Nakanishi K, et al. Canagliflozin attenuates liver cancer cell growth by inhibiting glucose uptake. Int J Cancer. 2018;142(8):1712‑22.
  • Faridi U, Al‑Mutairi F, Parveen H, Khateeb S. In‑vitro and in‑silico anticancer study of glimepiride and empagliflozin. Int J Life Sci Pharma Res. 2020;10:52‑57.
  • Xie Z, Wang F, Lin L, Duan S, Liu X, Li X, et al. An SGLT2 inhibitor modulates SHH expression via AMPK in cervical carcinoma cells. Cancer Lett. 2020;495:200-10.
  • Doğan H, Bahar MR, Çalışkan E, Tekin S, Uslu H, Akman F, et al. Cyclotriphosphazenes: synthesis, cytotoxic activity and docking studies. J Biomol Struct Dyn. 2022;40(7):3258‑72.
  • Korkmaz E, Tekin S. Cytotoxicity of myrtenal on human cancer cell lines. Ann Med Res. 2024;31(5):404‑8.
  • Sekerci G, Beytur L, Yuksel F, Tekin S. Anticancer effects of Meteorin‑like protein on human cancer cells. Ann Med Res. 2024;31(7):560‑4.
  • Beytur A, Tekin Ç, Çalışkan E, Tekin S, Koran K, Orhan Görgülü A, et al. Cyclotriphosphazene derivatives with hetero‑ring chalcones: cytotoxicity and DNA damage. Bioorg Chem. 2022;127:105997.
  • Oz S, Sekerci G, Yuksel F, Tekin S. Cytotoxic and genotoxic effects of nateglinide on various cancer cells. Ann Med Res. 2023;30(4):508‑12.
  • Karataş MO, Tekin S, Alici B, Sandal S. Cytotoxic effects of coumarin‑substituted benzimidazolium salts. J Chem Sci. 2019;131:1‑12.
  • Giovannucci E, Harlan DM, Archer MC, Bergenstal RM, Gapstur SM, Habel LA, et al. Diabetes and cancer: consensus report. Diabetes Care. 2010;33(7):1674‑85.
  • Bowers LW, Rossi EL, O’Flanagan CH, deGraffenried LA, Hursting SD. Insulin/IGF system in cancer. Front Endocrinol. 2015;6:77.
  • Vella V, Lappano R, Bonavita E, Maggiolini M, Clarke RB, Belfiore A, et al. Insulin/IGF axis and RAGE in cancer therapy. Endocr Rev. 2023;44(4):693‑723.
  • Zhao H, Wu K. Hyperglycemia in colorectal cancer prognosis. Am J Transl Res. 2024;16(5):2070‑81.
  • Seidu S, Alabraba V, Davies S, Newland‑Jones P, Fernando K, Bain SC, et al. SGLT2 inhibitors: new standard of care. Diabetes Ther. 2024;15(5):1099‑124.
  • Dutka M, Bobiński R, Francuz T, Garczorz W, Zimmer K, Ilczak T, et al. SGLT‑2 inhibitors in cancer treatment. Cancers (Basel). 2022;14(23).
  • Wright EM. SGLT2 and cancer. Pflugers Arch. 2020;472(9):1407‑14.
  • Shoda K, Tsuji S, Nakamura S, Egashira Y, Enomoto Y, Nakayama N, et al. Canagliflozin inhibits glioblastoma via AMPK. Cell Mol Neurobiol. 2023;43(2):879‑92.
  • Eliaa SG, Al‑Karmalawy AA, Saleh RM, Elshal MF. Empagliflozin + doxorubicin synergy in TNBC. ACS Pharmacol Transl Sci. 2020;3(6):1330‑38.
  • Bardaweel S, Issa A. SGLT transporters as cancer targets. J Pharm Pharm Sci. 2022;25:253‑65.
  • Wu W, Wang Y, Xie J, Fan S. Empagliflozin as anticancer drug. Discov Oncol. 2023;14(1):127.
  • Pandey A, Alcaraz Jr M, Saggese P, Soto A, Gomez E, Jaldu S, et al. SGLT2 inhibitors in cancer. Cancers. 2025;17(3):466.
  • Chiang CH, Chiang CH, Hsia Y, See XY, Wang S‑S, Chen Y‑J, et al. SGLT2 inhibitors in colorectal adenocarcinoma outcomes. ASCO; 2023.
  • Lai B, Xiao Y, Pu H, Cao Q, Jing H, Liu X. SGLT1 overexpression and prognosis in ovarian carcinoma. Arch Gynecol Obstet. 2012;285(5):1455‑61.
Toplam 33 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Tıbbi Biyokimya ve Metabolomik (Diğer)
Bölüm Araştırma Makalesi
Yazarlar

Engin Korkmaz 0000-0002-8365-2914

Tuba Keskin 0000-0002-9212-4021

Suat Tekin 0000-0002-2757-1802

Gönderilme Tarihi 24 Mart 2025
Kabul Tarihi 5 Kasım 2025
Yayımlanma Tarihi 31 Ocak 2026
Yayımlandığı Sayı Yıl 2026 Cilt: 7 Sayı: 1

Kaynak Göster

APA Korkmaz, E., Keskin, T., & Tekin, S. (2026). Investigation of Cytotoxic Effects of Empagliflozin on Caco-2, LNCaP and A2780 Human Cancer Cell Lines. Archives of Current Medical Research, 7(1), 1-8. https://doi.org/10.47482/acmr.1663941

Archives of Current Medical Research (ACMR), araştırmaları ücretsiz sunmanın daha büyük bir küresel bilgi alışverişini desteklediğini göz önünde bulundurarak, tüm içeriğe anında açık erişim sağlar. Kamunun erişimine açık olması, daha büyük bir küresel bilgi alışverişini destekler.

http://www.acmronline.org/