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Sains Malaysiana 52(5)(2023):
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
Received:
20 September 2022/Accepted: 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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*Corresponding author; email: nurulfarahana@ukm.edu.my
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