The In Vitro Cytotoxic Evaluation and Apoptotic Effects of Histone Deacetylase (HDAC) Inhibitory Drugs on Anaplastic Large Cell  Lymphoma (ALCL) Cell Lines

Mutaz Jama^l Al-Khreisat¹, Abdul Aziz Mohamed Yusoff², Faezahtul Arbaeyah  Hussain³, Muhammad Farid Johan^1,*

Abstract

Introduction: Anaplastic large cell lymphoma (ALCL) is a subtype of aggressive  peripheral T-cell lymphoma (PTCL). ALCL develops from T-lymphocytes (T-cells) and  approximately 10-20% of all T-non-Hodgkin lymphomas (T-NHL). CHOP  (cyclophosphamide, doxorubicin, vincristine, and prednisone) or CHOP-like  anthracycline-containing combination chemotherapy is common treatment used in  treating T-NHL including ALCL. The response to these regimes varies in ALCL  patients. Hence, it is hypothesised that the disease may exhibit variable molecular  biological behavior, which would affect how it responds to the conventional treatment. Alternative drugs with low toxicities and affecting epigenetic behavior like histone  deacetylase need to be explored as new drug option to ALCL. Our study aimed to  assess the cytotoxicity and apoptotic effects of histone deacetylase (HDAC) inhibitory  drugs (Trichostatin A and Panobinostat) on ALCL cell lines. Methods: ALCL cell lines  (SU-DHL-1, Ki-JK, and DL-40) were treated with different concentrations of Trichostatin A and Panobinostat to determine the cytotoxicity. 5-Azacytidine, an  epigenetic drug that inhibits DNA methylation was used as positive control. Half  maximal inhibitory concentration (IC50) values were determined by MTS cell viability  assays after 48h of treatment and calculated with GraphPad Prism Software version  3 using a dose–response inhibition curve. Apoptosis assays were performed using  Annexin V-FITC binding assays and analysed by flow cytometry. Results: Trichostatin  A and Panobinostat were cytotoxic against all ALCL cell lines and Ki-JK were the most  sensitive cell lines with IC50 211.7± 7.2 nM and 15.24± 3.4 nM, respectively. Trichostatin A and Panobinostat induced apopotosis in all ALCL cell lines with significantly higher apoptotic induction in Ki-JK (p<0.05). Conclusion: HDACs drugs  have significance effects on all ALCL cell line as the dose concentration were low, no  cytotoxicity, and have a great impact on apoptosis within a short period of time.

Keywords: ALCL, Lymphoma, Epigenetics, Trichostatin A, Panobinostat

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