Sains Malaysiana 49(6)(2020): 1421-1430

http://dx.doi.org/10.17576/jsm-2020-4906-20

Cytotoxic Effects of Organotin(IV) Dithiocarbamate Compounds with Different Functional Groups on Leukemic Cell Line, K-562

(Kesan Sitotoksik Sebatian Organotin(IV) Ditiokarbamat Berlainan Kumpulan Fungsian pada Sel Titisan Leukemia, K-562)

ASMAH HAMID¹*, MOHD AZAM AZMI¹, NOR FADILAH RAJAB¹, NORMAH AWANG² & NURUL FARHANA JUFRI¹

¹Programme of Biomedical Science, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Federal Territory, Malaysia

²Programme of Enviromental Health & Industrial Safety, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Federal Territory, Malaysia

Received: 19 July 2019/Accepted: 3 February 2020

ABSTRACT

Cancer is one of the main causes of mortality in the world. New compounds are currently being synthesized to overcome this disease. Organotin is getting more attention as anticancer agent due to its potent cytotoxic properties towards cancer cells. In this study, a series of newly synthesized organotin compounds known as dimethyltin(IV) (compound 1), dibutyltin(IV) (compound 2) and triphenyltin(IV)methylisoprophyldithiocarbamate (compound 3) have been assessed for their cytotoxic effect towards leukemic cell line K-562. MTT [3-(4,5-dimethylthiozol-2-yl)-2,5-diphenyl-tetrazolium bromide] assay was employed to determine the cytotoxic effect for each of the compounds at different time points and concentrations. Compound 2 and 3 exhibited potent cytotoxic effects towards K-562 cells with IC₅₀ values less than 2 µM. Compound 3 was found as the most toxic towards K-562 cells based on the lowest IC₅₀ value for 72 h period of treatment at 0.25 µM. Morphological observation was conducted with IC₅₀ values at 24, 48, and 72 h. Results showed that the changes were first observed as early as 24 h and the most significant changes were observed after 72 h period of treatment with the characteristic of apoptosis such as cell shrinkage and membrane blebbing. In addition, necrosis characteristic such as cell lysis and swelling had also been observed. Organotin(IV)methylisopropyldithiocarbamate with different functional groups affect the cytotoxic properties towards leukemic cells K-562 and these compounds have potential to be developed as an anticancer agent through structural modification.

Keywords: Anticancer; cytotoxic; leukemia; MTT assay; organotin

ABSTRAK

Kanser merupakan penyebab utama kematian di seluruh dunia. Bagi menangani masalah ini, sebatian baru disintesis. Organotin semakin mendapat perhatian sebagai agen anti-kanser kerana mempunyai kesan antitoksik terhadap sel kanser. Dalam kajian ini, suatu siri sintesis bahan organotin dikenali sebagai dimetiltin (IV) (bahan 1), dibutiltin (bahan 2) dan trifeniltin (IV) metilisoprofilditiokarbamat (bahan 3) diuji untuk kesan sitotoksik terhadap sel leukemia K-562. Ujian MTT [3-(4,5-dimetiltiozol-2-il)-2,5-difenil-tetrazolium bromida] digunakan bagi menentukan kesan sitotoksik untuk setiap bahan pada tempoh masa dan kepekatan berbeza. Bahan 2 dan 3 menunjukkan kesan sitotoksik yang kuat terhadap sel K-562 dengan nilai IC₅₀ kurang daripada 2 µM. Bahan 3 menunjukkan kesan paling toksik terhadap sel K-562 berdasarkan nilai IC₅₀ paling rendah selama 72 jam pada kepekatan 0.25 µM. Pemerhatian morfologi pada nilai IC₅₀ pada 24, 48 dan 72 jam menunjukkan perubahan morfologi berlaku seawal jam ke-24 dan perubahan signifikan pada 72 jam rawatan dengan ciri-ciri apoptosis seperti pengecutan sel dan pertumbuhan luar membran sel. Selain itu, sel nekrosis seperti sel lisis dan pembengkakan sel juga diperhatikan. Sebagai rumusan, bahan organotin (IV) metilisoprofilditiokarbamat dengan kumpulan fungsi berbeza memberikan kesan sitotoksik terhadap sel dan mempunyai potensi untuk dibangunkan sebagai agen anti-kanser melalui pengubahsuaian struktur.

Kata kunci: Anti-kanser; leukemia; organotin; sitotoksik; ujian MTT

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*Corresponding author; email: asmah0901@ukm.edu.my