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BORAKS PROSTAT KANSERİ HÜCRELERİNDE OTOFAJİ YOLAĞINI REGÜLE EDEREK PROLİFERASYONU ENGELLER

Yıl 2026, Cilt: 27 Sayı: 2 , 175 - 181 , 16.04.2026
https://doi.org/10.18229/kocatepetip.1683292
https://izlik.org/JA57CT48RA

Öz

AMAÇ: Otofaji, kanser hücrelerinin hayatta kalmasında ve te-daviye karşı direnç geliştirmesinde kritik bir rol oynamaktadır. Esansiyel bir iz element olan bor, çeşitli biyolojik süreçlerde yer almaktadır; ancak, prostat kanserinde boraksın antitümör etki-leri üzerine yapılan araştırmalar sınırlı olup, bu bağlamda otofa-jinin rolü hâlen yeterince anlaşılmamıştır. Bu çalışma, boraksın DU-145 insan prostat kanseri hücrelerinde otofaji üzerindeki etkilerini ve bu etkilerin moleküler düzeydeki mekanizmaları araştırılmıştır.GEREÇ VE YÖNTEM: : DU-145 hücreleri in vitro koşullarda kültürlenmiş ve boraks ile muamele edilmiştir. Hücre canlılığı ve proliferasyonu, MTT (3-(4,5-dimetiltiazol-2-il)-2,5-difenil-tetrazolyum bromür) testi ve BrdU (5-bromo-2'-deoksiüridin) inkorporasyon yöntemi ile değerlendirilmiştir. Sitotoksik bo-raks konsantrasyonları belirlendikten sonra, otofaji ile ilişkili belirteçler olan Beclin1, mikrotübül ilişkili protein 1 hafif zincir 3 (LC3-II) ve sequestosome-1 (SQSTM1) ekspresyon düzeyleri ölçülmüştür.BULGULAR: Elde edilen sonuçlar, boraksın DU-145 hücre canlı-lığını doz bağımlı olarak anlamlı biçimde azalttığını göstermiş-tir. Ayrıca, boraks hücre proliferasyonunu baskılamış ve hücre döngüsünün S fazındaki hücre oranını önemli ölçüde azaltmış-tır. Moleküler düzeyde ise boraks uygulaması, SQSTM1’in azal-masına, Beclin1 ve LC3-II’nin ise artmasına yol açarak otofajinin indüklendiğine işaret etmiştir.SONUÇ: Bu bulgular, boraksın DU-145 prostat kanseri hücre-lerinin proliferasyonunu otofajik yolakları aktive ederek inhibe ettiğini göstermektedir. Gözlemlenen etkilerin, büyük ölçüde Beclin1/LC3-II/SQSTM1 sinyal yolunun modülasyonu ile ilişkili olduğu düşünülmektedir. Ayrıca, boraksın bir otofaji aktivatö-rü ile kombinasyonu, antitümör etkinliğini artırabilir ve prostat kanseri tedavisinde umut verici bir strateji sunabilir.

Kaynakça

  • 1. Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87-108.
  • 2. De Nunzio C, Presicce F, Lombardo R, et al. Physical activity as a risk factor for prostate cancer diagnosis: a prospective biopsy cohort analysis. BJU Int. 2016;117(6B):29-35.
  • 3. Malvezzi M, Bertuccio P, Rosso T, et al. European cancer mortality predictions for the year 2015: does lung cancer have the highest death rate in EU women? Ann Oncol. 2015;26:779-86.
  • 4. Cha EK, Eastham JA. Chemotherapy and novel therapeutics before radical prostatectomy for high-risk clinically localized prostate cancer. Urol Oncol. 2015;33(5):217-25.
  • 5. Parzych KR, Klionsky DJ. An overview of autophagy: morphology, mechanism, and regulation. Antioxid Redox Signal. 2014;20(3):460-73.
  • 6. Tanida I, Ueno T, Kominami E. LC3 conjugation system in mammalian autophagy. Int J Biochem Cell Biol. 2004;36:2503-18.
  • 7. Debnath J, Gammoh N, Ryan KM. Autophagy and autophagy-related pathways in cancer. Nat Rev Mol Cell Biol. 2023;24(8):560-75.
  • 8. Livesey KM, Tang D, Zeh HJ, Lotze MT. Autophagy inhibition in combination cancer treatment. Curr Opin Investig Drugs. 2009;10(12):1269-79.
  • 9. Jones TM, Carew JS, Nawrocki ST. Therapeutic Targeting of Autophagy for Renal Cell Carcinoma Therapy. Cancers (Basel). 2020;12(5):1185.
  • 10. Eroglu Gunes C. Boric Acid Shows ER Stress and Apoptosis Mediated Anticancer Activity in Human Pancreatic Cancer MIA PaCa-2 and PANC- 1 Cells. Selcuk Med J. 2023;39(1):1-6.
  • 11. Devirian TA, Volpe SL. The physiological effects of dietary boron. Crit Rev Food Sci Nutr. 2003;43(2):219-31.
  • 12. Khaliq H, Juming Z, Ke-Mei P. The Physiological Role of Boron on Health. Biol Trace Elem Res. 2018;186(1):31-51.
  • 13. Barranco WT, Eckhert CD. Boric acid inhibits human prostate cancer cell proliferation. Cancer Lett. 2004;216(1):21-9.
  • 14. Hacioglu C, Kar F, Kacar S, Sahinturk V, Kanbak G. High Concentrations of Boric Acid Trigger Concentration- Dependent Oxidative Stress, Apoptotic Pathways and Morphological Alterations in DU-145 Human Prostate Cancer Cell Line. Biol Trace Elem Res. 2020;193(2):400-9.
  • 15. Cui Y, Winton MI, Zhang ZF, et al. Dietary boron intake and prostate cancer risk. Oncol Rep. 2004;11(4):887-92.
  • 16. Xu Y, Yu H, Qin H, et al. Inhibition of autophagy enhances cisplatin cytotoxicity through endoplasmic reticulum stress in human cervical cancer cells. Cancer Lett. 2012;314(2):232-43.
  • 17. Rosenfeld MR, Ye X, Supko JG, et al. A phase I/II trial of hydroxychloroquine in conjunction with radiation therapy and concurrent and adjuvant temozolomide in patients with newly diagnosed glioblastoma multiforme. Autophagy. 2014;10(8):1359-68.
  • 18. Koca HB, Köken T, Akan T. Effect of Apıum Graveolens Extracts on Caspase-3, -8, -9 and Apaf-1 in Lncap Cells. KTD. 2024;25:300–6.
  • 19. Tuncer C, Hacioglu C. Borax induces ferroptosis of glioblastoma by targeting HSPA5/NRF2/GPx4/GSH pathways. J Cell Mol Med. 2024;28(7):e18206.
  • 20. Hacioglu C, Kar F, Davran F, Tuncer C. Borax regulates iron chaperone- and autophagy-mediated ferroptosis pathway in glioblastoma cells. Environ Toxicol. 2023;38(7):1690-1701.
  • 21. Hacioglu C, Oral D. Borax affects cellular viability by inducing ER stress in hepatocellular carcinoma cells by targeting SLC12A5. J Cell Mol Med. 2024;28(10):e18380.
  • 22. Feng Y, He D, Yao Z, Klionsky DJ. The machinery of macroautophagy. Cell Res. 2014;24(1):24-41.
  • 23. Klionsky DJ, Codogno P. The mechanism and physiological function of macroautophagy. J Innate Immun. 2013;5(5):427-33.
  • 24. Münz C. Regulation of innate immunity by the molecular machinery of macroautophagy. Cell Microbiol. 2014;16(11):1627-36.
  • 25. Hönscheid P, Datta K, Muders MH. Autophagy: detection, regulation and its role in cancer and therapy response. Int J Radiat Biol. 2014;90(8):628-35.
  • 26. Patel AS, Morse D, Choi AM. Regulation and functional significance of autophagy in respiratory cell biology and disease. Am J Respir Cell Mol Biol. 2013;48(1):1-9.
  • 27. Lorin S, Hamaï A, Mehrpour M, Codogno P. Autophagy regulation and its role in cancer. Semin Cancer Biol. 2013;23(5):361-79.
  • 28. Thorburn A, Thamm DH, Gustafson DL. Autophagy and cancer therapy. Mol Pharmacol. 2014;85(6):830-38.
  • 29. Chen HY, White E. Role of autophagy in cancer prevention. Cancer Prev Res (Phila). 2011;4(7):973-83.
  • 30. Nie C, Zhou J, Qin X, et al. Diosgenin‑induced autophagy and apoptosis in a human prostate cancer cell line. Mol Med Rep. 2016;14(5):4349-59.
  • 31. Won KY, Kim GY, Lim SJ, et al. Autophagy is related to the hedgehog signaling pathway in human gastric adenocarcinoma: prognostic significance of Beclin-1 and Gli2 expression in human gastric adenocarcinoma. Pathol Res Pract. 2015;211(4):308-15.
  • 32. Salminen A, Kaarniranta K, Kauppinen A. Beclin 1 interactome controls the crosstalk between apoptosis, autophagy and inflammasome activation: impact on the aging process. Ageing Res Rev. 2013;12(2):520-34.
  • 33. Slobodkin MR, Elazar Z. The Atg8 family: multifunctional ubiquitin-like key regulators of autophagy. Essays Biochem. 2013;55:51-64.
  • 34. Romao S, Münz C. LC3-associated phagocytosis. Autophagy. 2014;10(3):526-8.
  • 35. Ouyang DY, Xu LH, He XH, et al. Autophagy is differentially induced in prostate cancer LNCaP, DU145 and PC-3 cells via distinct splicing profiles of ATG5. Autophagy. 2013;9(1):20-32.
  • 36. Korolchuk VI, Menzies FM, Rubinsztein DC. A novel link between autophagy and the ubiquitin-proteasome system. Autophagy. 2009;5(6):862-3.

Borax Inhibits Proliferation by Regulating the Autophagy Pathway in Prostate Cancer Cells

Yıl 2026, Cilt: 27 Sayı: 2 , 175 - 181 , 16.04.2026
https://doi.org/10.18229/kocatepetip.1683292
https://izlik.org/JA57CT48RA

Öz

OBJECTIVE: Autophagy plays a critical role in the survival of cancer cells and the development of resistance to therapeutic agents. Boron, an essential trace element, is involved in various biological processes; however, limited research has investigated the antitumor effects of borax in prostate cancer, and the role of autophagy in this context remains inadequately understood. The present study investigated the effects and underlying mechanisms of borax on autophagy in DU-145 human prostate cancer cells.
MATERIAL AND METHODS: DU-145 cells were cultured in vitro and treated with borax. Cell viability and proliferation were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the 5-bromo-2'-deoxyuridine (BrdU) incorporation method. Following the determination of cytotoxic borax concentrations, the expression levels of autophagy-related markers Beclin1, microtubule-associated protein 1 light chain 3 (LC3-II), and sequestosome-1 (SQSTM1) were measured.
RESULTS: The results demonstrated that borax significantly reduced DU-145 cell viability in a dose-dependent manner. Moreover, borax suppressed cell proliferation and markedly decreased the proportion of cells in the S phase of the cell cycle. At the molecular level, borax treatment led to a reduction of SQSTM1 and an increase of Beclin1 and LC3-II, indicating the induction of autophagy.
CONCLUSIONS: These findings suggest that borax inhibits the proliferation of DU-145 prostate cancer cells by activating autophagic pathways. The observed effects appear to be mediated through the modulation of the Beclin1/LC3-II/SQSTM1 signaling axis. Furthermore, the combination of borax with an autophagy activator may enhance its antitumor efficacy, presenting a promising strategy for therapeutic intervention in prostate cancer.

Kaynakça

  • 1. Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87-108.
  • 2. De Nunzio C, Presicce F, Lombardo R, et al. Physical activity as a risk factor for prostate cancer diagnosis: a prospective biopsy cohort analysis. BJU Int. 2016;117(6B):29-35.
  • 3. Malvezzi M, Bertuccio P, Rosso T, et al. European cancer mortality predictions for the year 2015: does lung cancer have the highest death rate in EU women? Ann Oncol. 2015;26:779-86.
  • 4. Cha EK, Eastham JA. Chemotherapy and novel therapeutics before radical prostatectomy for high-risk clinically localized prostate cancer. Urol Oncol. 2015;33(5):217-25.
  • 5. Parzych KR, Klionsky DJ. An overview of autophagy: morphology, mechanism, and regulation. Antioxid Redox Signal. 2014;20(3):460-73.
  • 6. Tanida I, Ueno T, Kominami E. LC3 conjugation system in mammalian autophagy. Int J Biochem Cell Biol. 2004;36:2503-18.
  • 7. Debnath J, Gammoh N, Ryan KM. Autophagy and autophagy-related pathways in cancer. Nat Rev Mol Cell Biol. 2023;24(8):560-75.
  • 8. Livesey KM, Tang D, Zeh HJ, Lotze MT. Autophagy inhibition in combination cancer treatment. Curr Opin Investig Drugs. 2009;10(12):1269-79.
  • 9. Jones TM, Carew JS, Nawrocki ST. Therapeutic Targeting of Autophagy for Renal Cell Carcinoma Therapy. Cancers (Basel). 2020;12(5):1185.
  • 10. Eroglu Gunes C. Boric Acid Shows ER Stress and Apoptosis Mediated Anticancer Activity in Human Pancreatic Cancer MIA PaCa-2 and PANC- 1 Cells. Selcuk Med J. 2023;39(1):1-6.
  • 11. Devirian TA, Volpe SL. The physiological effects of dietary boron. Crit Rev Food Sci Nutr. 2003;43(2):219-31.
  • 12. Khaliq H, Juming Z, Ke-Mei P. The Physiological Role of Boron on Health. Biol Trace Elem Res. 2018;186(1):31-51.
  • 13. Barranco WT, Eckhert CD. Boric acid inhibits human prostate cancer cell proliferation. Cancer Lett. 2004;216(1):21-9.
  • 14. Hacioglu C, Kar F, Kacar S, Sahinturk V, Kanbak G. High Concentrations of Boric Acid Trigger Concentration- Dependent Oxidative Stress, Apoptotic Pathways and Morphological Alterations in DU-145 Human Prostate Cancer Cell Line. Biol Trace Elem Res. 2020;193(2):400-9.
  • 15. Cui Y, Winton MI, Zhang ZF, et al. Dietary boron intake and prostate cancer risk. Oncol Rep. 2004;11(4):887-92.
  • 16. Xu Y, Yu H, Qin H, et al. Inhibition of autophagy enhances cisplatin cytotoxicity through endoplasmic reticulum stress in human cervical cancer cells. Cancer Lett. 2012;314(2):232-43.
  • 17. Rosenfeld MR, Ye X, Supko JG, et al. A phase I/II trial of hydroxychloroquine in conjunction with radiation therapy and concurrent and adjuvant temozolomide in patients with newly diagnosed glioblastoma multiforme. Autophagy. 2014;10(8):1359-68.
  • 18. Koca HB, Köken T, Akan T. Effect of Apıum Graveolens Extracts on Caspase-3, -8, -9 and Apaf-1 in Lncap Cells. KTD. 2024;25:300–6.
  • 19. Tuncer C, Hacioglu C. Borax induces ferroptosis of glioblastoma by targeting HSPA5/NRF2/GPx4/GSH pathways. J Cell Mol Med. 2024;28(7):e18206.
  • 20. Hacioglu C, Kar F, Davran F, Tuncer C. Borax regulates iron chaperone- and autophagy-mediated ferroptosis pathway in glioblastoma cells. Environ Toxicol. 2023;38(7):1690-1701.
  • 21. Hacioglu C, Oral D. Borax affects cellular viability by inducing ER stress in hepatocellular carcinoma cells by targeting SLC12A5. J Cell Mol Med. 2024;28(10):e18380.
  • 22. Feng Y, He D, Yao Z, Klionsky DJ. The machinery of macroautophagy. Cell Res. 2014;24(1):24-41.
  • 23. Klionsky DJ, Codogno P. The mechanism and physiological function of macroautophagy. J Innate Immun. 2013;5(5):427-33.
  • 24. Münz C. Regulation of innate immunity by the molecular machinery of macroautophagy. Cell Microbiol. 2014;16(11):1627-36.
  • 25. Hönscheid P, Datta K, Muders MH. Autophagy: detection, regulation and its role in cancer and therapy response. Int J Radiat Biol. 2014;90(8):628-35.
  • 26. Patel AS, Morse D, Choi AM. Regulation and functional significance of autophagy in respiratory cell biology and disease. Am J Respir Cell Mol Biol. 2013;48(1):1-9.
  • 27. Lorin S, Hamaï A, Mehrpour M, Codogno P. Autophagy regulation and its role in cancer. Semin Cancer Biol. 2013;23(5):361-79.
  • 28. Thorburn A, Thamm DH, Gustafson DL. Autophagy and cancer therapy. Mol Pharmacol. 2014;85(6):830-38.
  • 29. Chen HY, White E. Role of autophagy in cancer prevention. Cancer Prev Res (Phila). 2011;4(7):973-83.
  • 30. Nie C, Zhou J, Qin X, et al. Diosgenin‑induced autophagy and apoptosis in a human prostate cancer cell line. Mol Med Rep. 2016;14(5):4349-59.
  • 31. Won KY, Kim GY, Lim SJ, et al. Autophagy is related to the hedgehog signaling pathway in human gastric adenocarcinoma: prognostic significance of Beclin-1 and Gli2 expression in human gastric adenocarcinoma. Pathol Res Pract. 2015;211(4):308-15.
  • 32. Salminen A, Kaarniranta K, Kauppinen A. Beclin 1 interactome controls the crosstalk between apoptosis, autophagy and inflammasome activation: impact on the aging process. Ageing Res Rev. 2013;12(2):520-34.
  • 33. Slobodkin MR, Elazar Z. The Atg8 family: multifunctional ubiquitin-like key regulators of autophagy. Essays Biochem. 2013;55:51-64.
  • 34. Romao S, Münz C. LC3-associated phagocytosis. Autophagy. 2014;10(3):526-8.
  • 35. Ouyang DY, Xu LH, He XH, et al. Autophagy is differentially induced in prostate cancer LNCaP, DU145 and PC-3 cells via distinct splicing profiles of ATG5. Autophagy. 2013;9(1):20-32.
  • 36. Korolchuk VI, Menzies FM, Rubinsztein DC. A novel link between autophagy and the ubiquitin-proteasome system. Autophagy. 2009;5(6):862-3.
Toplam 36 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Üroloji
Bölüm Araştırma Makalesi
Yazarlar

Ekrem Başaran 0000-0001-8319-512X

Ceyhan Hacıoğlu 0000-0002-0993-6118

Sare Uyurca 0000-0003-2869-9629

Dursun Baba 0000-0002-4779-6777

Arda Taşkın Taşkıran 0000-0003-4556-3475

Ahmet Yıldırım Balık 0000-0001-8051-5802

Gönderilme Tarihi 24 Nisan 2025
Kabul Tarihi 21 Ağustos 2025
Yayımlanma Tarihi 16 Nisan 2026
DOI https://doi.org/10.18229/kocatepetip.1683292
IZ https://izlik.org/JA57CT48RA
Yayımlandığı Sayı Yıl 2026 Cilt: 27 Sayı: 2

Kaynak Göster

APA Başaran, E., Hacıoğlu, C., Uyurca, S., Baba, D., Taşkıran, A. T., & Balık, A. Y. (2026). BORAKS PROSTAT KANSERİ HÜCRELERİNDE OTOFAJİ YOLAĞINI REGÜLE EDEREK PROLİFERASYONU ENGELLER. Kocatepe Tıp Dergisi, 27(2), 175-181. https://doi.org/10.18229/kocatepetip.1683292
AMA 1.Başaran E, Hacıoğlu C, Uyurca S, Baba D, Taşkıran AT, Balık AY. BORAKS PROSTAT KANSERİ HÜCRELERİNDE OTOFAJİ YOLAĞINI REGÜLE EDEREK PROLİFERASYONU ENGELLER. KTD. 2026;27(2):175-181. doi:10.18229/kocatepetip.1683292
Chicago Başaran, Ekrem, Ceyhan Hacıoğlu, Sare Uyurca, Dursun Baba, Arda Taşkın Taşkıran, ve Ahmet Yıldırım Balık. 2026. “BORAKS PROSTAT KANSERİ HÜCRELERİNDE OTOFAJİ YOLAĞINI REGÜLE EDEREK PROLİFERASYONU ENGELLER”. Kocatepe Tıp Dergisi 27 (2): 175-81. https://doi.org/10.18229/kocatepetip.1683292.
EndNote Başaran E, Hacıoğlu C, Uyurca S, Baba D, Taşkıran AT, Balık AY (01 Nisan 2026) BORAKS PROSTAT KANSERİ HÜCRELERİNDE OTOFAJİ YOLAĞINI REGÜLE EDEREK PROLİFERASYONU ENGELLER. Kocatepe Tıp Dergisi 27 2 175–181.
IEEE [1]E. Başaran, C. Hacıoğlu, S. Uyurca, D. Baba, A. T. Taşkıran, ve A. Y. Balık, “BORAKS PROSTAT KANSERİ HÜCRELERİNDE OTOFAJİ YOLAĞINI REGÜLE EDEREK PROLİFERASYONU ENGELLER”, KTD, c. 27, sy 2, ss. 175–181, Nis. 2026, doi: 10.18229/kocatepetip.1683292.
ISNAD Başaran, Ekrem - Hacıoğlu, Ceyhan - Uyurca, Sare - Baba, Dursun - Taşkıran, Arda Taşkın - Balık, Ahmet Yıldırım. “BORAKS PROSTAT KANSERİ HÜCRELERİNDE OTOFAJİ YOLAĞINI REGÜLE EDEREK PROLİFERASYONU ENGELLER”. Kocatepe Tıp Dergisi 27/2 (01 Nisan 2026): 175-181. https://doi.org/10.18229/kocatepetip.1683292.
JAMA 1.Başaran E, Hacıoğlu C, Uyurca S, Baba D, Taşkıran AT, Balık AY. BORAKS PROSTAT KANSERİ HÜCRELERİNDE OTOFAJİ YOLAĞINI REGÜLE EDEREK PROLİFERASYONU ENGELLER. KTD. 2026;27:175–181.
MLA Başaran, Ekrem, vd. “BORAKS PROSTAT KANSERİ HÜCRELERİNDE OTOFAJİ YOLAĞINI REGÜLE EDEREK PROLİFERASYONU ENGELLER”. Kocatepe Tıp Dergisi, c. 27, sy 2, Nisan 2026, ss. 175-81, doi:10.18229/kocatepetip.1683292.
Vancouver 1.Ekrem Başaran, Ceyhan Hacıoğlu, Sare Uyurca, Dursun Baba, Arda Taşkın Taşkıran, Ahmet Yıldırım Balık. BORAKS PROSTAT KANSERİ HÜCRELERİNDE OTOFAJİ YOLAĞINI REGÜLE EDEREK PROLİFERASYONU ENGELLER. KTD. 01 Nisan 2026;27(2):175-81. doi:10.18229/kocatepetip.1683292

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