Araştırma Makalesi
Bortezomib ve C vitamini Kombinasyonunun HL-60 Akut Promyelositik Lösemi Hücrelerindeki Etkisinin Değerlendirilmesi
Öz
Amaç: C vitamini, tedaviye bağlı yan etkileri azaltma ve kanser hücrelerinin kemoterapötik ajanlara duyarlılığını arttırmak için farklı kanser tedavilerinde kullanılmaktadır. Bunun yanında C vitamininin serbest radikal süpürücü özelliği, inhibitör etkisi ve oksidatif stresi indükleme rolü tedavilerin etkinliğini değiştirebilmektedir. Bu çalışmada lösemi tedavisinde kemoterapötik-sitotoksik ajan olarak kullanılan Bortezomib ve C vitamininin ve bunların kombinasyonlarının HL-60 akut promyelositik lösemi hücrelerindeki etkilerinin araştırılması amaçlandı.
Materyal ve Metod: HL-60 hücreleri, Bortezomib (1-100 nM), C vitamini (1-100 µM) konsantrasyonları ve bunların kombinasyonları ile 24 saat ile inkübe edildi. Bortezomib ve C vitamininin monoterapötik ve bunların kombinasyonunun sitotoksik etkileri MTT yöntemiyle, genotoksik etkiler Comet assay yöntemiyle ve intraselüler reaktif oksijen türleri (ROS) düzeyi DCFH-DA floresan prob yöntemiyle analiz edildi.
Bulgular: HL-60 hücrelerinde Bortezomib’in konsantrasyonla ilişkili olarak sitotoksik ve genotoksik etkiler oluşturduğu (p˂0.001), C vitaminin ise (100 µM hariç) sitotoksik ve genotoksik etki oluşturmadığı bulundu (p˃0.05). Bortezomib+C vitamini kombinasyonlarında yüksek C vitamini konsantrasyonlarının daha yüksek sitotoksik, genotoksik etkiler oluşturduğu ve hücre içi ROS seviyelerini artırdığı bulundu (p˂0.001). Ancak bu etkiler bortezomib’in monoterapötik etkisi kadar güçlü değildi.
Sonuç: HL-60 akut promyelositik lösemi hücrelerinde Bortezomib’in monoterapötik etkilerine karşılık Bortezomib+C vitamini kombinasyonu daha az sitotoksisite, genotoksisite ve hücre içi ROS oluşumuna sebep olmuştur. C vitamininin bu potansiyel etkileri kanser tedavisinde göz önünde bulundurulmalıdır. Bu sonuçların farklı lösemi hücre hatları, in vivo ve preklinik çalışmalarla desteklenmesi lösemi tedavisinde onkolojik etkinliği artırmaya yardımcı olabilir.
Anahtar Kelimeler
Bortezomib C vitamini Sitotoksisite Genotoksisite Hücre içi ROS
Destekleyen Kurum
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Proje Numarası
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Teşekkür
Bu çalışmada kullanılan HL-60 hücre hattını temin eden ve teknik destek sağlayan Gaziantep Üniversitesi Tıp Fakültesi Tıbbi Biyokimya Anabilim dalında görevli Dr. Hasan Ulusal’a teşekkür ederim.
Kaynakça
- Lawenda BD, Kelly KM, Ladas EJ, Sagar SM, Vickers A, Blum-berg JB. Should Supplemental Antioxidant Administration Be Avoided During Chemotherapy and Radiation Therapy? JNCI J Natl Cancer Inst. 2008; 100(11): 773–83.
- Huang R-FS, Huang S-M, Lin B-S, Hung C-Y, Lu H-T. N-Acetylcysteine, Vitamin C and Vitamin E Diminish Homocys-teine Thiolactone-Induced Apoptosis in Human Promyeloid HL-60 Cells. J Nutr. 2002; 132(8): 2151–6.
- Taşkın A, Tarakçıoğlu M, Ulusal H, Örkmez M, Taysı S. Idaru-bicin-bromelain combination sensitizes cancer cells to con-ventional chemotherapy. Iran J Basic Med Sci. 2019; 22(10): 1172–8.
- Harvie M. Nutritional Supplements and Cancer: Potential Benefits and Proven Harms. Am Soc Clin Oncol Educ B. 2014; (34): e478–86.
- Padayatty SJ, Sun AY, Chen Q, Espey MG, Drisko J, Levine M. Vitamin C: Intravenous Use by Complementary and Al-ternative Medicine Practitioners and Adverse Effects. PLoS One. 2010; 5(7): e11414.
- Bedhiafi T, Inchakalody VP, Fernandes Q, Mestiri S, Billa N, Uddin S, et al. The potential role of vitamin C in empowe-ring cancer immunotherapy. Biomed Pharmacother. 2022; 146: 112553.
- Catley L, Anderson KC. Velcade and Vitamin C: Too Much of a Good Thing? Clin Cancer Res. 2006; 12(1): 3–4.
- Lee SJ, Jeong J, Lee I, Lee J, Jung JH, Park HY, et al. Effect of High-dose Vitamin C Combined With Anti-cancer Treatment on Breast Cancer Cells. Anticancer Res. 2019; 39(2): 751-758.
- Chen Q, Espey MG, Krishna MC, Mitchell JB, Corpe CP, Buettner GR, et al. Pharmacologic ascorbic acid concentrati-ons selectively kill cancer cells: Action as a pro-drug to deli-ver hydrogen peroxide to tissues. Proc Natl Acad Sci. 2005; 102(38): 13604–9.
- Pires AS, Marques CR, Encarnação JC, Abrantes AM, Marques IA, Laranjo M, et al. Ascorbic Acid Chemosensiti-zes Colorectal Cancer Cells and Synergistically Inhibits Tu-mor Growth. Frontiers in Physiology. 2018; 9: 911.
- Ngo B, Van Riper JM, Cantley LC, Yun J. Targeting cancer vulnerabilities with high-dose vitamin C. Nat Rev Cancer. 2019; 19(5): 271–82.
- Reang J, Sharma PC, Thakur VK, Majeed J. Understanding the therapeutic potential of ascorbic acid in the battle to overcome cancer. Biomolecules. 2021; 11(8): 1130.
- Perrone G, Hideshima T, Ikeda H, Okawa Y, Calabrese E, Gorgun G, et al. Ascorbic acid inhibits antitumor activity of bortezomib in vivo. Leukemia. 2009; 23(9): 1679–86.
- Llobet D, Eritja N, Encinas M, Sorolla A, Yeramian A, Scho-enenberger JA, et al. Antioxidants block proteasome inhibi-tor function in endometrial carcinoma cells. Anticancer Drugs. 2008 ; 19(2): 115-24.
- Park J, Cho J, Song EJ. Ubiquitin–proteasome system (UPS) as a target for anticancer treatment. Arch Pharm Fricker LD. Proteasome Inhibitor Drugs. Annu Rev Pharma-col Toxicol. 2020; 60(1): 457–76.
- Lioni M, Noma K, Snyder A, Klein-Szanto A, Diehl JA, Rustgi AK, et al. Bortezomib induces apoptosis in esophageal squamous cell carcinoma cells through activation of the p38 mitogen-activated protein kinase pathway. Mol Cancer Ther. 2008 ;7(9): 2866–75.
- Voorhees PM, Dees EC, O’Neil B, Orlowski RZ. The Protea-some as a Target for Cancer Therapy. Clin Cancer Res. 2003; 9(17): 6316–25.
- Korani M, Korani S, Zendedel E, Jaafari M, Sathyapalan T, Sahebkar A. Utilization of Lipid-Based Nanoparticles to Imp-rove the Therapeutic Benefits of Bortezomib. Anticancer Agents Med Chem. 2020; 20: 643-650.
- Nie D, Huang K, Yin S, Li Y, Xie S, Ma L, et al. Synergis-tic/additive interaction of valproic acid with bortezomib on proliferation and apoptosis of acute myeloid leukemia cells. Leuk Lymphoma. 2012; 53(12): 2487–95.
- Zou W, Yue P, Lin N, He M, Zhou Z, Lonial S, et al. Vitamin C Inactivates the Proteasome Inhibitor PS-341 in Human Can-cer Cells. Clin Cancer Res. 2006; 12(1): 273–80.
- Kliková K, Štefaniková A, Pilchová I, Hatok J, Chudý P, Chu-dej J, et al. Differential impact of bortezomib on HL-60 and K562 cells. Gen Physiol Biophys. 2015; 34: 33–42.
- Kramarenko GG, Wilke WW, Dayal D, Buettner GR, Schafer FQ. Ascorbate enhances the toxicity of the photodynamic action of Verteporfin in HL-60 cells. Free Radic Biol Med. 2006; 40(9): 1615–27.
- Singh NP, McCoy MT, Tice RR, Schneider EL. A simple tech-nique for quantitation of low levels of DNA damage in indi-vidual cells. Exp Cell Res. 1988; 175(1): 184–91.
- Duran E, Taşkın S, Pehlivan B, Çelik H. DNA damage and changes in oxidized biomolecules in COVID-19 patients trea-ted in intensive care units: a single center experience. Eur Rev Med Pharmacol Sci. 2023; 27(13): 6414–21.
- D’Andrea GM. Use of Antioxidants During Chemotherapy and Radiotherapy Should Be Avoided. CA Cancer J Clin. 2005; 55(5): 319–21.
- Bairati I, Meyer F, Jobin E, Gélinas M, Fortin A, Nabid A, et al. Antioxidant vitamins supplementation and mortality: A randomized trial in head and neck cancer patients. Int J Cancer. 2006; 119(9): 2221–4.
- Salganik RI. The Benefits and Hazards of Antioxidants: Cont-rolling Apoptosis and Other Protective Mechanisms in Can-cer Patients and the Human Population. J Am Coll Nutr. 2001; 20: 464S-472S. Available at: https://doi.org/10.1080/07315724.2001.10719185
- Shinozaki K, Hosokawa Y, Hazawa M, Kashiwakura I, Oku-mura K, Kaku T, et al. Ascorbic Acid Enhances Radiation-induced Apoptosis in an HL60 Human Leukemia Cell Line. J Radiat Res. 2011; 52(2): 229–37.
- González-Montero J, Chichiarelli S, Eufemi M, Altieri F, Saso L, Rodrigo R. Ascorbate as a Bioactive Compound in Cancer Therapy: The Old Classic Strikes Back. Molecules. 2022; 17: 12.
- Yedjou CG, Thuisseu L, Tchounwou C, Gomes M, Howard C, Tchounwou P. Ascorbic acid potentiation of arsenic trioxide anticancer activity against acute promyelocytic leukemia. Arch Drug Inf. 2009; 2(4): 59–65.
- Karasavvas N, Cárcamo JM, Stratis G, Golde DW. Vitamin C protects HL60 and U266 cells from arsenic toxicity. Blood. 2005; 105(10): 4004–12.
Evaluation of the Effect of Bortezomib and Vitamin C Combination in HL-60 Acute Promyelocytic Leukemia Cells
Öz
Proje Numarası
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Kaynakça
- Lawenda BD, Kelly KM, Ladas EJ, Sagar SM, Vickers A, Blum-berg JB. Should Supplemental Antioxidant Administration Be Avoided During Chemotherapy and Radiation Therapy? JNCI J Natl Cancer Inst. 2008; 100(11): 773–83.
- Huang R-FS, Huang S-M, Lin B-S, Hung C-Y, Lu H-T. N-Acetylcysteine, Vitamin C and Vitamin E Diminish Homocys-teine Thiolactone-Induced Apoptosis in Human Promyeloid HL-60 Cells. J Nutr. 2002; 132(8): 2151–6.
- Taşkın A, Tarakçıoğlu M, Ulusal H, Örkmez M, Taysı S. Idaru-bicin-bromelain combination sensitizes cancer cells to con-ventional chemotherapy. Iran J Basic Med Sci. 2019; 22(10): 1172–8.
- Harvie M. Nutritional Supplements and Cancer: Potential Benefits and Proven Harms. Am Soc Clin Oncol Educ B. 2014; (34): e478–86.
- Padayatty SJ, Sun AY, Chen Q, Espey MG, Drisko J, Levine M. Vitamin C: Intravenous Use by Complementary and Al-ternative Medicine Practitioners and Adverse Effects. PLoS One. 2010; 5(7): e11414.
- Bedhiafi T, Inchakalody VP, Fernandes Q, Mestiri S, Billa N, Uddin S, et al. The potential role of vitamin C in empowe-ring cancer immunotherapy. Biomed Pharmacother. 2022; 146: 112553.
- Catley L, Anderson KC. Velcade and Vitamin C: Too Much of a Good Thing? Clin Cancer Res. 2006; 12(1): 3–4.
- Lee SJ, Jeong J, Lee I, Lee J, Jung JH, Park HY, et al. Effect of High-dose Vitamin C Combined With Anti-cancer Treatment on Breast Cancer Cells. Anticancer Res. 2019; 39(2): 751-758.
- Chen Q, Espey MG, Krishna MC, Mitchell JB, Corpe CP, Buettner GR, et al. Pharmacologic ascorbic acid concentrati-ons selectively kill cancer cells: Action as a pro-drug to deli-ver hydrogen peroxide to tissues. Proc Natl Acad Sci. 2005; 102(38): 13604–9.
- Pires AS, Marques CR, Encarnação JC, Abrantes AM, Marques IA, Laranjo M, et al. Ascorbic Acid Chemosensiti-zes Colorectal Cancer Cells and Synergistically Inhibits Tu-mor Growth. Frontiers in Physiology. 2018; 9: 911.
- Ngo B, Van Riper JM, Cantley LC, Yun J. Targeting cancer vulnerabilities with high-dose vitamin C. Nat Rev Cancer. 2019; 19(5): 271–82.
- Reang J, Sharma PC, Thakur VK, Majeed J. Understanding the therapeutic potential of ascorbic acid in the battle to overcome cancer. Biomolecules. 2021; 11(8): 1130.
- Perrone G, Hideshima T, Ikeda H, Okawa Y, Calabrese E, Gorgun G, et al. Ascorbic acid inhibits antitumor activity of bortezomib in vivo. Leukemia. 2009; 23(9): 1679–86.
- Llobet D, Eritja N, Encinas M, Sorolla A, Yeramian A, Scho-enenberger JA, et al. Antioxidants block proteasome inhibi-tor function in endometrial carcinoma cells. Anticancer Drugs. 2008 ; 19(2): 115-24.
- Park J, Cho J, Song EJ. Ubiquitin–proteasome system (UPS) as a target for anticancer treatment. Arch Pharm Fricker LD. Proteasome Inhibitor Drugs. Annu Rev Pharma-col Toxicol. 2020; 60(1): 457–76.
- Lioni M, Noma K, Snyder A, Klein-Szanto A, Diehl JA, Rustgi AK, et al. Bortezomib induces apoptosis in esophageal squamous cell carcinoma cells through activation of the p38 mitogen-activated protein kinase pathway. Mol Cancer Ther. 2008 ;7(9): 2866–75.
- Voorhees PM, Dees EC, O’Neil B, Orlowski RZ. The Protea-some as a Target for Cancer Therapy. Clin Cancer Res. 2003; 9(17): 6316–25.
- Korani M, Korani S, Zendedel E, Jaafari M, Sathyapalan T, Sahebkar A. Utilization of Lipid-Based Nanoparticles to Imp-rove the Therapeutic Benefits of Bortezomib. Anticancer Agents Med Chem. 2020; 20: 643-650.
- Nie D, Huang K, Yin S, Li Y, Xie S, Ma L, et al. Synergis-tic/additive interaction of valproic acid with bortezomib on proliferation and apoptosis of acute myeloid leukemia cells. Leuk Lymphoma. 2012; 53(12): 2487–95.
- Zou W, Yue P, Lin N, He M, Zhou Z, Lonial S, et al. Vitamin C Inactivates the Proteasome Inhibitor PS-341 in Human Can-cer Cells. Clin Cancer Res. 2006; 12(1): 273–80.
- Kliková K, Štefaniková A, Pilchová I, Hatok J, Chudý P, Chu-dej J, et al. Differential impact of bortezomib on HL-60 and K562 cells. Gen Physiol Biophys. 2015; 34: 33–42.
- Kramarenko GG, Wilke WW, Dayal D, Buettner GR, Schafer FQ. Ascorbate enhances the toxicity of the photodynamic action of Verteporfin in HL-60 cells. Free Radic Biol Med. 2006; 40(9): 1615–27.
- Singh NP, McCoy MT, Tice RR, Schneider EL. A simple tech-nique for quantitation of low levels of DNA damage in indi-vidual cells. Exp Cell Res. 1988; 175(1): 184–91.
- Duran E, Taşkın S, Pehlivan B, Çelik H. DNA damage and changes in oxidized biomolecules in COVID-19 patients trea-ted in intensive care units: a single center experience. Eur Rev Med Pharmacol Sci. 2023; 27(13): 6414–21.
- D’Andrea GM. Use of Antioxidants During Chemotherapy and Radiotherapy Should Be Avoided. CA Cancer J Clin. 2005; 55(5): 319–21.
- Bairati I, Meyer F, Jobin E, Gélinas M, Fortin A, Nabid A, et al. Antioxidant vitamins supplementation and mortality: A randomized trial in head and neck cancer patients. Int J Cancer. 2006; 119(9): 2221–4.
- Salganik RI. The Benefits and Hazards of Antioxidants: Cont-rolling Apoptosis and Other Protective Mechanisms in Can-cer Patients and the Human Population. J Am Coll Nutr. 2001; 20: 464S-472S. Available at: https://doi.org/10.1080/07315724.2001.10719185
- Shinozaki K, Hosokawa Y, Hazawa M, Kashiwakura I, Oku-mura K, Kaku T, et al. Ascorbic Acid Enhances Radiation-induced Apoptosis in an HL60 Human Leukemia Cell Line. J Radiat Res. 2011; 52(2): 229–37.
- González-Montero J, Chichiarelli S, Eufemi M, Altieri F, Saso L, Rodrigo R. Ascorbate as a Bioactive Compound in Cancer Therapy: The Old Classic Strikes Back. Molecules. 2022; 17: 12.
- Yedjou CG, Thuisseu L, Tchounwou C, Gomes M, Howard C, Tchounwou P. Ascorbic acid potentiation of arsenic trioxide anticancer activity against acute promyelocytic leukemia. Arch Drug Inf. 2009; 2(4): 59–65.
- Karasavvas N, Cárcamo JM, Stratis G, Golde DW. Vitamin C protects HL60 and U266 cells from arsenic toxicity. Blood. 2005; 105(10): 4004–12.
Toplam 31 adet kaynakça vardır.
Ayrıntılar
| Birincil Dil | Türkçe |
|---|---|
| Konular | Hücre Fizyolojisi |
| Bölüm | Araştırma Makalesi |
| Yazarlar | |
| Proje Numarası | - |
| Erken Görünüm Tarihi | 29 Ağustos 2023 |
| Yayımlanma Tarihi | 31 Ağustos 2023 |
| Gönderilme Tarihi | 13 Ağustos 2023 |
| Kabul Tarihi | 28 Ağustos 2023 |
| Yayımlandığı Sayı | Yıl 2023 Cilt: 20 Sayı: 2 |
Harran Üniversitesi Tıp Fakültesi Dergisi / Journal of Harran University Medical Faculty