Öz
Background: A chemotherapeutic agent, vincristine, inhibits spindle fiber formation in both the neoplastic and normal cells. Reversal of apoptotic effects may be exerted by folic acid and beta-carotene addition in vitro. In this study, we aimed to investigate the effects of folic acid and beta-carotene added alone or together on vincristine induced apoptosis in human multiple myeloma cell line ARH77 and human chronic myeloid leukemia cell line K562 cultures. Materials and Methods: Apoptosis was induced by 10-5M vincristine added to the cultures for 24, 48 and 72 hours. Folic acid and beta-carotene were added alone or together in 10-3 M and 10-7M respectively. Cell viability of every culture was determined after which at least 500 cells were analyzed for apoptotic features. Statistical comparisons of ratios were made with two proportion z test. Results: In ARH77 cells, no significant decrease in apoptotic cell ratios were determined after folic acid and beta-carotene addition alone or together (p >0.05). Whereas, in K562 cells, after incubation with vincristine for 24 hours, apoptotic cell ratios were significantly reduced by folic acid and beta-carotene treatment one at a time or together (p <0.05). Conclusion: Reversal of apoptotic effects is dependent on type and metabolic activity of the target cells as well as the induction mechanism of the agent used. Key words: Vincristine, apoptosis, folic acid, beta-carotene, ARH77, K562
Anahtar Kelimeler
Kaynakça
- Ryungsa K.,Recent Advances in Understanding the Cell Death Pathways Activated by Anticancer Therapy Cancer (2005) 103 (8): 1551-60
- Ricci M.S, Zong WX., Chemotherapeutic Approaches for Targeting Cell Death Pathways Oncologist 2006;11;342-57
- Kuo C., Hsieh H.,Pan W.,Chen C. et al. BPR0L075, a Novel Synthetic Indole Compound with Antimitotic Activity in Human Cancer Cells, Exerts Effective Antitumoral Activity in Vivo Can res. 64,(2004) 4621–4628,
- Fenech M., Recommended dietary allowances (RDAs) for genomic stability Mutation Research 480-481 (2001) 51-4
- Prasad K.N. Multiple Dietary antioxidants enhance the efficiacy of standart and experimental cancer therapies and decrease their toxicity Integr Cancer Ther. 2004 3(4):310-22
- Prakash P., Russell R.M., Krinsky N.I. In Vitro Inhibition of Proliferation of Estrogen-Dependent and Estrogen- Independent Human Breast Cancer Cells Treated with Carotenoids or Retinoids J Nutr. 2001 131(5):1574-80.
- Yilmaz Z, Karabay G, Oktem M, et al. The apoptotic effects of mitomycin C on human endometrial cell cultures and reversal of its effects by β-carotene and folic acid. Acta Physiol Hung. 2006 93(1):41-51
- Wang X., Fenech M.: A comparison of folic acid and 5-methyltetrahydrofolate for prevention of DNA damage and cell death in human lymphocytes in vitro, Mutagenesis 2003, 18: 81-6
- Fenech M. The role of folic acid and Vitamin B12 in genomic stability of human cells Mutation Research 475 (2001) 57-67
- Zijno A., Andreoli C., Leopardi P., et al. Folate status, metabolic genotype, and biomarkers of genotoxicity in healthy subjects, Carcinogenesis, 2003, 24: 1097-103
- Giles F.J., Kantarjian H., O’brien S., et al. Results of therapy with interferon alpha and cyclic combination chemotherapy in patients with philadelphia chromosome positive chronic myelogenous leukemia in early chronic phase Leuk. Lymphoma 2001 41 (3-4): 309-19
- Jimenez-Zepeda VH, Dominguez-Martinez VJ. Vincristine, doxorubicin, and dexamethasone or thalidomide plus dexamethasone for newly diagnosed patients with multiple myeloma? Eur J Haematol. 2006 77(3):239-44.
- Hanukoglu I.: Antioxidant protective mechanisms against reactive oxygen species (ROS) generated by mitochondrial P450 systems in steroidogenic cells, Drug Metab Rev. 2006;38:171-96
- Park In-C, Park MJ, Hwang CS, et al. MMC induced apotosis in a caspase-dependent and Fas/CD95-independent manner in human gastric adenocarsinoma cells. Cancer Letters. 2000;158:125-32
- Bal F., Sahin F.I., Yirmibes M., et al. The in vitro effect of β-carotene and mitomycin C on SCE frequency in Down’s syndrome lymphocyte Cultures Tohoku J. Exp. Med. 1998, 184, 295-300
- Groninger E., Meeuwsen-de Boer G.J., De Graaf S.S.N., et al. Vincristine induced apoptosis in acute lymphoblastic leukaemia cells: A mitochondrial controlled pathway regulated by reactive oxygen species? Internatıonal Journal Of Oncology 2002 21: 1339-45,
Öz
Amaç: Bir kemoterapötik ajan olan vinkristin, iğ iplikçiklerinin oluşumunu hem neoplastik hem normal hücrelerde engellemektedir. Daha önce yapılan çalışmalarda farklı kemoterapötik ajanlarla uyarılan apoptozisin, ortama folik asit ve β-karoten eklenmesi ile in vitro olarak geri dönüşümü gösterilmiştir. Bu çalışmada insan multiple myeloma (MM) hücre dizisi ARH77 ve insan kronik myeloid lösemi (KML) hücre dizisi K562 kültürlerinde vinkristinin uyardığı apoptozise folik asit ve β-karotenin tek tek ve birlikte etkilerinin araştırılması amaçlanmıştır. Gereç ve Yöntem: İnsan MM hücre dizisi ARH77 ve insan KML hücre dizisi K562 standart hücre kültürü koşullarında üretilerek 24, 48 ve 72 saat süre ve 10-5M konsantrasyonda vinkristin ile muamele ederek apoptozis uyarılmıştır. Folik asit ve β-karoten tek tek veya birlikte sırasıyla 10-5 ve 10-7 M konsantrasyonlarda eklenerek etkileri izlenmiştir. Her kültürden canlı hücre oranı belirlendikten sonra, en az 500 hücre apoptotik bulgular açısından analiz edilmiştir. İstatistiksel analizler iki oran z testi ile yapılmıştır. Bulgular: ARH77 hücrelerinde vinkristinin indüklediği apoptotik hücre oranlarında folik asit ve β-karotenin tek tek veya birlikte eklenmesiyle anlamlı azalma belirlenmemiştir (p>0.05). K562 hücrelerinde ise 24 saat süreyle uygulanan vinkristinin indüklediği apoptozis hem folik asit hem de β-karotenin tek tek veya birlikte eklenmesiyle istatistiksel olarak anlamlı düzeyde azalmıştır (p<0.05). Anahtar kelimeler: Vinkristin, apoptozis, folik asit, beta-karoten, ARH77, K562
Anahtar Kelimeler
Kaynakça
- Ryungsa K.,Recent Advances in Understanding the Cell Death Pathways Activated by Anticancer Therapy Cancer (2005) 103 (8): 1551-60
- Ricci M.S, Zong WX., Chemotherapeutic Approaches for Targeting Cell Death Pathways Oncologist 2006;11;342-57
- Kuo C., Hsieh H.,Pan W.,Chen C. et al. BPR0L075, a Novel Synthetic Indole Compound with Antimitotic Activity in Human Cancer Cells, Exerts Effective Antitumoral Activity in Vivo Can res. 64,(2004) 4621–4628,
- Fenech M., Recommended dietary allowances (RDAs) for genomic stability Mutation Research 480-481 (2001) 51-4
- Prasad K.N. Multiple Dietary antioxidants enhance the efficiacy of standart and experimental cancer therapies and decrease their toxicity Integr Cancer Ther. 2004 3(4):310-22
- Prakash P., Russell R.M., Krinsky N.I. In Vitro Inhibition of Proliferation of Estrogen-Dependent and Estrogen- Independent Human Breast Cancer Cells Treated with Carotenoids or Retinoids J Nutr. 2001 131(5):1574-80.
- Yilmaz Z, Karabay G, Oktem M, et al. The apoptotic effects of mitomycin C on human endometrial cell cultures and reversal of its effects by β-carotene and folic acid. Acta Physiol Hung. 2006 93(1):41-51
- Wang X., Fenech M.: A comparison of folic acid and 5-methyltetrahydrofolate for prevention of DNA damage and cell death in human lymphocytes in vitro, Mutagenesis 2003, 18: 81-6
- Fenech M. The role of folic acid and Vitamin B12 in genomic stability of human cells Mutation Research 475 (2001) 57-67
- Zijno A., Andreoli C., Leopardi P., et al. Folate status, metabolic genotype, and biomarkers of genotoxicity in healthy subjects, Carcinogenesis, 2003, 24: 1097-103
- Giles F.J., Kantarjian H., O’brien S., et al. Results of therapy with interferon alpha and cyclic combination chemotherapy in patients with philadelphia chromosome positive chronic myelogenous leukemia in early chronic phase Leuk. Lymphoma 2001 41 (3-4): 309-19
- Jimenez-Zepeda VH, Dominguez-Martinez VJ. Vincristine, doxorubicin, and dexamethasone or thalidomide plus dexamethasone for newly diagnosed patients with multiple myeloma? Eur J Haematol. 2006 77(3):239-44.
- Hanukoglu I.: Antioxidant protective mechanisms against reactive oxygen species (ROS) generated by mitochondrial P450 systems in steroidogenic cells, Drug Metab Rev. 2006;38:171-96
- Park In-C, Park MJ, Hwang CS, et al. MMC induced apotosis in a caspase-dependent and Fas/CD95-independent manner in human gastric adenocarsinoma cells. Cancer Letters. 2000;158:125-32
- Bal F., Sahin F.I., Yirmibes M., et al. The in vitro effect of β-carotene and mitomycin C on SCE frequency in Down’s syndrome lymphocyte Cultures Tohoku J. Exp. Med. 1998, 184, 295-300
- Groninger E., Meeuwsen-de Boer G.J., De Graaf S.S.N., et al. Vincristine induced apoptosis in acute lymphoblastic leukaemia cells: A mitochondrial controlled pathway regulated by reactive oxygen species? Internatıonal Journal Of Oncology 2002 21: 1339-45,
Ayrıntılar
| Birincil Dil | Türkçe |
|---|---|
| Bölüm | Makaleler |
| Yazarlar | |
| Yayımlanma Tarihi | 1 Ağustos 2007 |
| Yayımlandığı Sayı | Yıl 2007 Cilt: 14 Sayı: 4 |