Sains Malaysiana 52(5)(2023): 1513-1521

http://doi.org/10.17576/jsm-2023-5205-14

Diorganotin(IV) N-methyl-N-phenethyldithiocarbamate Compounds Induce Cytotoxicity via Apoptosis in K562 Human Erythroleukaemia Cells

(Sebatian Diorganostanum(IV) N-metil-N-fenetilditiokarbamat Mengaruh Sitotoksisiti melalui Apoptosis terhadap Sel Eitroleukemia Manusia, K562)

SHARIFAH NADHIRA SYED ANNUAR, NURUL FARAHANA KAMALUDIN^*, NORMAH AWANG, KOK MENG CHAN& NORRAPHAT UTTRAPHAN PIM

Center for Toxicology and Health Risk Studies, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia

Diserahkan: 20 September 2022/Diterima: 11 April 2023

Abstract

Imatinib mesylate (IM), a leading treatment for chronic myeloid leukaemia (CML), has sparked worries about the possibility of CML patients developing a resistance to it. As a result, researchers are becoming more interested in organotin(IV) compounds due to their strong potential to be developed as anticancer agents and employed as an option to address the issues regarding IM-resistance therapy. Generally, this study is to determine the cytotoxicity induced by diorganotin(IV) dithiocarbamate compounds in K562 human erythroleukaemia cells. The two novel diorganotin(IV) compounds namely diphenyltin(IV) N-methyl-N-phenethyldithiocarbamate (C1) and dibutyltin(IV) N-methyl-N-phenethyldithiocarbamate (C2) were assessed their cytotoxicity via MTT [3-(4-5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay and mode of cell death via Annexin V-FITC/PI assay with the duration treatment of 24 h. Both compounds displayed strong cytotoxicity in K562 cells. At concentration of 4.2 µM for C1 and 1.6 µM for C2, both compounds were able to induce 49.70% and 46.83% apoptotic events, respectively. The changes in cells' morphological can also be seen 24 h after being exposed to the compounds at their respective IC₅₀ doses. The findings demonstrated that the morphology of the cells was similar to apoptotic features, including cell shrinkage and the production of apoptotic bodies, meanwhile, the low levels of necrotic cells (<1%) also can be seen via cell lysis. In conclusion, both compounds possess the potential as antileukaemia drugs nevertheless, further studies on their action mechanism are required to ratify their qualities and suitability in the research of anticancer drugs development.

Keywords: Cancer; carbamate; cell death; organotin(IV); toxicity

Abstrak

Imatinib mesylate (IM) yang merupakan rawatan utama bagi Leukemia Mieloid Kronik (CML) telah mendatangkan kebimbangan kerana pesakit CML berkemungkinan menunjukkan kesan rintangan terhadap penggunaan IM. Oleh yang demikian, sebatian organostanum(IV) telah menarik minat para penyelidik kerana berpotensi tinggi untuk dibangunkan sebagai agen antikanser dan alternatif bagi menangani isu rintangan terhadap IM. Secara amnya, kajian ini adalah untuk menentukan kesitotoksikan aruhan sebatian diorganostanum(IV) ditiokarbamat terhadap sel K562 eritroleukemia manusia. Dua sebatian baharu diorganostanum(IV)  iaitu difenilstanum(IV) N-metil-N-fenetilditiokarbamat (C1) dan dibutilstanum(IV) N-metil-N-fenetilditiokarbamat (C2) telah dinilai kesan ketoksikannya melalui asai 3-(4-5-dimetiltiazol-2-il)-2,5-difeniltetrazolium bromida (MTT) dan mod kematian sel melalui asai Annexin V-FITC/PI dalam tempoh 24 jam rawatan. Kedua-dua sebatian menunjukkan kesan sitotoksisiti yang kuat terhadap sel K562. Pada kepekatan 4.2 µM bagi C1 dan 1.6 µM bagi C2, masing-masing mampu mengaruh 49.70% dan 46.83% sel apoptotik. Malahan, perubahan pada morfologi sel yang menunjukkan ciri-ciri apoptosis antaranya termasuk pengecutan sel dan pembentukan jasad apoptotik, juga dapat dilihat selepas 24 jam rawatan mengikut dos IC₅₀ sementara itu, tahap sel nekrotik yang rendah (<1%) dapat dilihat melalui lisis sel. Kesimpulannya, kedua-dua sebatian berpotensi untuk dibangunkan sebagai dadah antileukemia, namun kajian lanjutan berkaitan mekanisme tindakannya adalah perlu bagi mengesahkan kualiti dan tahap kesesuaiannya dalam penyelidikan pembangunan dadah antikanser.

Kata kunci: Kanser; karbamat; kematian sel; ketoksikan; organostanum(IV)

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^*Pengarang untuk surat-menyurat; email: nurulfarahana@ukm.edu.my