اثر ضدتوموری والپروئیک اسید و 25،1 دی هیدروکسی ویتامین D3 بر سلولهای سرطانی HL-60

نویسنده

دانشگاه ملایر

چکیده
گزارش شده که 1، 25دی هیدروکسی ویتامین D3 یک شکل فعال ویتامینD رشد تعدادی از سلول­های سرطانی پوست، پروستات، سینه، کولون و لوسمی را مهار می­کند. والپروئیک اسید، به عنوان یک مهارکنندۀ قوی هیستون داستیلاز، همچنین نقش مهمی در مهار تکثیر سلول­های تومور ایفا می­کند. با این حال، تا کنون هیچ گزارشی در مورد همکاری بین والپروئیک اسید و 1، 25دی هیدروکسی ویتامین D3 برای اثر ضد سرطانی وجود ندارد. هدف از تحقیق حاضر ارزیابی این بود که آیا دوزهای کم1، 25دی هیدروکسی ویتامینD3 سمیت والپروئیک اسید را تقویت می­کند و آیا این عمل از طریق مکانیزم های آپوپتوز انجام می­گیرد. در این مطالعه سلول هایHL-60 با غلظت های مختلف والپروئیک اسید و 1، 25دی هیدروکسی ویتامین D3 به تنهایی و در ترکیب با یکدیگر در 24ساعت تیمار شدند. درصد زنده بودن سلول­ها به روش MTT سنجیده شد و سپس برای بررسی نوع مرگ سلولی از رنگ ­آمیزی Hoechst استفاده شد. مطالعه حاضر نشان داد که1، 25دی هیدروکسی ویتامین D3 اثر آنتی توموری والپروئیک اسید را افزایش می­دهد. همچنین نتایج حاصل از رنگ آمیزی سلول­ها نشان داد که والپروئیک اسید و 1، 25دی هیدروکسی ویتامین D3 باعث القاء آپوپتوز در سلول­های HL-60 می­شوند. در کل ترکیب جدید والپروئیک اسید و 1، 25دی هیدروکسی ویتامین D3 هم افزایی اثر ضد تکثیری و القاء آپوپتوز در روی سلول­های سرطانی HL-60 را نشان داد.

کلیدواژه‌ها


عنوان مقاله English

Anti-tumor effects of valproic acid and 1, 25 dihydroxy vitamin D3 on HL-60 cancer cells

نویسنده English

Maryam Rihimi
چکیده English

11, 25 dihydroxy vitamin D3, an active metabolite of vitamin­D3 has been reported to inhibit the growth of number neoplasms such as prostate, breast, colorectal, leukemia and skin cancers. Valproic acid, as a potent histone deacetylase inhibitor, also plays an important role in inhibition of proliferation of tumor cells. However, there are no reports so far on the cooperation between valproic acid and vitamin­ D3 for anti-leukemic effect. The goal of the present research was to evaluate whether low doses of vitamin D3 potentiate the toxicity of valproic acid and whether this toxic action is mediated via apoptotic mechanisms. In this study HL-60 cells were treated either with different concentrations of valproic acid and vitamin­ D3 alone and in combination with each other for 24 hours. Cell survival was determined by MTT assay and then Hoechst staining was used to determine the type of death cell. This present study indicates that vitamin ­D3 potentiates the antitumor effects of valproic acid. Also, the results of staining cells showed that valproic acid and vitamin ­D3 induced apoptosis in HL-60 cells. In total, the new combination of valproic acid and vitamin D3 showed synergistic anti-proliferative effect and induced apoptosis on HL-60 cancer cells.

کلیدواژه‌ها English

Acute promyelocytic leukemia
anti-proliferation
Apoptosis
differentiation
histone deacetylase inhibitor
Chen, B.A., Zhao, H.H., Gao, C., Shao, Z.Y., Xia, G.H. and Dohner, K. 2007. Effects of sodium valproate on proliferation and apoptosis of human myelodysplastic syndromes cell line MUTZ-1. – Ai Zheng. 26: 1323-1329.
Chirumbolo, S. 2015.Vitamin D3 in cancer prevention and therapy: the nutritional issue. – Horm. Mol. Biol. Clin. Investig. 23: 71-8.
Chou, T.C. 2006. Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. – Phar-macol. Rev. 58: 621-681.
Rogers, C.S., Yedjou, C.G., Sutton, D.J. and Paul, B.T. 2014. Vitamin D3 potentiates the antitumorigenic effects of arsenic trioxide in human leukemia (HL-60) cells. – Exp. Hematol. Oncol. 3: 9-17.
Corcoran, A., Nadkarni, S., Yasuda, K., Sakaki, T., Brown, G., Kutner, A. and Marcinkowska, E. 2016. Biological evaluation of double point modified analogues of 1, 25-Dihydroxyvitamin D₂ as potential anti-leukemic agents. – Int. J. Mol. Sci. 17: 91-101.
Datta-Mitra, A., Mitra, A., Ray, R., Raychaudhuri, S.P. and Kundu-Raychaudhuri, S. 2013. 1, 25-Dihydroxyvi-tamin D3-3-bromoacetate, a novel vitamin D analog induces immunosuppression through PI-3K/Akt/mTOR signaling cascade. – Int. Immuno-pharmacol. 17: 744-51.
Debeb, B.G., Xu, W., Mok, H., Li, L., Robertson, F. and Ueno, N.T. 2010. Differential radiose-nsitizing effect of valproic acid in differentiation versus self-renewal promoting culture cond-itions. – Int. J. Radiat. Oncol. Biol. Phys. 76: 889-95.
Duenas, G.A., Candelaria, M., Perez, P.C., Peza, C.E, Cruz, H.E. and Herrera, L. 2008. Valproic acid as epigenetic cancer drug: percl-inical, clinical and tran-scriptional effect on solid tumors. – Cancer Treat. Rev. 34: 206-222.
Harikrishnan, K.N., Karagiannis, T.C., Chow, M.Z. and El-Osta, A. 2008. Effect of valproic acid on radiation-induced DNA damage in euch-romatic and heterochromatic compartments. – Cell Cycle 7: 468-76.
Hicks, C.W., Pandya, M.M. and Fernande, Z. 2011. Valproate for the treatment of medication-induced impulse-control disorder in three patients with parkinsons disease. – Parkinsonism Relat. Disord. 17: 379-381.
Hikita, K., Hattori, N., Takeda, A., Yamakage, Y., Shibata, R., Yamada, S., Kato, K., Murata, T., Tanaka, H. and Kaneda, N. 2017. Potent apoptosis-inducing activity of erypoegin K, an isoflavone isolated from Erythrina poeppigiana, against human leukemia HL-60 cells. – J. Nat. Med. 18: 1147-9.
Imran, A., Qamar, H.Y., Ali, Q., Naeem, H., Riaz, M., Amin, S., Kanwal ,N., Ali, F., Sabar, M.F. and Nasir, I.A. 2017. Role of Molecular Biology in Cancer Treatment: A Review Article. – Iran J. Public Health. 46: 1475-1485.
Kamada, R., Kudoh, F., Yoshimura, F., Tanino, K. and Sakaguchi, K. 2017. Inhibition of Ser/Thr phosphatase PPM1D induces neutrophil differen-tiation in HL-60 cells. – J. Biochem. 162: 303-308.
Karagiannis, T.C., Kn, H. and El-Osta, A. 2006. The epigenetic modifier, valproic acid, enhances radiation sensitivity. – Epigenetics 1: 131-7.
Kostrouchova, M., Kostrouch, Z. and Kostrouchova, M. 2007. Valproic acid molecular lead to multiple regul-atory pathways. – Folia Biological. 53: 37-49.
Li, Y.Q., Yin, S.M., Feng, S.Q., Nie, D.N., Xie, S.F., Ma, L.P., Wang, X.J. and Wu, Y.D. 2010. Effect of valproic acid on apoptosis of leukemia HL-60 cells and expression of h-tert gene. – Zhongguo Shi Yan Xue Ye Xue Za Zhi. 18:1445-50.
Li, X.N., Shu, Q., Su, J.M.F., Perlaky, L., Blaney, S.M. and Lau, C.C. 2005.Valproic acid induces growth arrest, apoptosis, and senescence in medullobla-stomas by increasing histonhyperacetylation and regulation expression of p21Cip1, CDK4, and CMYC. – Mol. Cancer Ther. 4: 1912-1922.
Loscher, W. 2002. Basic pharmacology of valpr-oate: a review after 35 years of clinical use for the treatment of epilepsy. – CNS Drugs. 16: 669-694.
Luong, Q.T. and Koeffler, P.H. 2005. Vitamin D comp-ounds in leukemia. – Hematol. Oncol. 97: 195-202.
Mohseni-Kouchesfahani, H., Nabioni, M., Khosravi, Z. and Rahimi, M. 2017. Honey bee venom combined with 1, 25-dihydroxyvitamin D3as a highly efficient inducer of differentiation in human acute myeloid leukemia cells. – J. Cancer Res. Ther. 13: 544-549.
Rowinsky, E.K. 1997. The development and clinical utility of the taxane class of antimicrotubule chemo-therapy agents. – Annu. Rev. Med. 48: 353 –74.
Shi, M., Ren, X., Wang, X., Wang, H., Liu, G., Yuan, X., Zheng, S., Yu L., Pan, S., Song, G., Guo, Q., Li, L., Zhang, X., Zhang, Z., Ding, H. and Jiang, G. 2016. A novel combination of oridonin and valproic acid in enhancement of apoptosis induction of HL-60 leuk-emia cells. – Int. J. Oncol. 48: 734-746.
Spira, A.I. and Carducci, M.A. 2003. Differentiation therapy. – Curr. Opin. Pharmacol. 3: 338-343.
Wang, Q., Harrison, J.S., Uskokovic, M., Kutner, A. and Studzinski, G.P. 2005. Translational study of Vitamin D differentiation therapy of myeloid leuk-emia: Effects of the combination with a p38 MAPK inhibitor and an antioxidant. Leukemia. 19: 1812-7.
Wang, Q., Salman, H., Danilenko, M. and Studzinski, G.P. 2005. Cooperation between antioxidants and 1,25‑dihydroxyvitamin D3 in induction of leukemia HL60 cell differentiation through the JNK/AP-1/Egr-1 pathway. – J. Cell Physiol. 204: 964-74.
Zhang, T.D., Chen, G.Q., Wang, Z.G., Wang, Z.Y., Chen, S.J. and Chen, Z. 2001. Arsenic trioxide, a therapeutic agent for APL. – Oncogene 20: 7146-7153.

  • تاریخ دریافت 18 خرداد 1405
  • تاریخ انتشار 18 خرداد 1405