Sains Malaysiana 50(3)(2021): 821-828

http://doi.org/10.17576/jsm-2021-5003-22

Effects of Apigenin, Luteolin, and Quercetin on the Natural Killer (NK-92) Cells Proliferation: A Potential Role as Immunomodulator

(Kesan Apigenin, Luteolin dan Quersetin terhadap Pertumbuhan Sel Pembunuh Asli (NK-92): Peranan Berpotensi sebagai Kawalan Imuniti)

AUNG MYO OO@MOHD HASYM¹, NASIR MAT NOR¹*, LIYANA HAZWANI MOHD ADNAN¹, NOR ZIDAH BINTI AHMAD¹, ABDI WIRA SEPTAMA², NIK NURUL NAJIHAH¹, OHN MAR LWIN³ & NORDIN SIMBAK¹

¹Faculty of Medicine, Universiti Sultan Zainal Abidin, 20400 City Campus, Kuala Terengganu, Terengganu Darul Iman, Malaysia

²Research Center for Chemistry, Indonesian Institute of Sciences, Kawasan PUSPIPTEK Serpong, Tangerang Selatan, Banten 15314, Indonesia

³Physiology unit, Faculty of Medicine, Lincoln University College Kelana Jaya, 47301, Petaling Jaya, Selangor Darul Ehsan, Malaysia

Received: 16 June 2020/Accepted: 10 August 2020

ABSTRACT

Cancer can be classified as a fourth leading cause of death in Malaysia. There is a continuous effort by scientists in finding alternative cure to cancer due to the known side effects of chemotherapy and radiation therapy as well as recurrences. One of the latest methods to kill cancerous cells is by using immune cells known as natural killer (NK) cells. Flavonoids such as flavone and flavonol are also known for their antioxidant, anti-inflammatory, immunomodulatory and anticancer properties. This study was carried out to determine the role of flavonoid compounds of apigenin, luteolin, and quercetin to facilitate the growth of NK-92 cells. NK-92 cell line was grown in tissue culture flasks containing α- Minimum Essential Medium (MEM) medium enriched with L-glutamine, 12.5% fetal bovine serum, 12.5% horse serum, 0.2 mM myo-inositol, 0.02 mM folic acid, and 100 - 200 U/mL recombinant interleukin 2 (IL-2). The cell viability was determined via trypan blue staining where the cells were manually counted by a haemocytometer. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to determine the cell viability of NK-92 cells after treatment with apigenin, luteolin, and quercetin. Results showed a dose-dependent proliferative effects of apigenin, luteolin, and quercetin on the proliferation of NK-92 cells showing the highest percentage of proliferation at 100 µg/mL for all compounds (*P < 0.05). However, exceeding the dose of 100 µg/mL had resulted in a decline of cell proliferations percentage. Based on these findings, flavonoid compounds comprising apigenin, luteolin and quercetin were able to induce proliferative effects on NK-92 cells.

Keywords: Apigenin; flavonoids; luteolin; natural killer cells; quercetin

ABSTRAK

Kanser boleh dikelaskan sebagai penyebab kematian ke-empat tertinggi di Malaysia. Usaha berterusan para saintis dalam mencari kaedah lain untuk merawat kanser disebabkan kesan sampingan yang diketahui berpunca daripada rawatan kemo dan radiasi serta pertumbuhan semula sel kanser. Salah satu daripada kaedah terkini untuk membunuh sel kanser adalah dengan menggunakan sel imun yang dikenali sebagai sel pembunuh asli (sel NK). Sekumpulan flavonoid seperti flavon dan flavonol juga dikenali dengan ciri antioksidan, antiradang, kawalan imuniti dan anti-kanser. Kajian ini telah dijalankan untuk menentukan peranan beberapa sebatian flavonoid iaitu apigenin, luteolin dan quersetin dalam membantu pertumbuhan sel NK-92. Sel NK-92 dibiakkan di dalam bekas tisu kultur yang mengandungi media α-medium penting minimum (α-MEM) yang diperkaya dengan L-glutamin, 12.5% serum sapi janin, 12.5% serum kuda, 0.2 mM myo-inositol, 0.02 mM asid folik dan 100 - 200 U/mL rekombinan interleukin 2 (IL-2). Kadar pertumbuhan sel telah dikenal pasti melalui pewarnaan tripan biru dengan sel tersebut dihitung secara manual menggunakan hemositometer. Ujian 3-(4,5-dimetilthiazol-2-yl)-2,5-difeniltetrazolium bromida (MTT) telah digunakan untuk menentukan pertumbuhan sel NK-92 setelah dirawat dengan apigenin, luteolin dan quersetin. Keputusan menunjukkan bahawa kesan perkembangan pendosan-kerbergantungan daripada apigenin, luteolin dan quersetin ke atas pertumbuhan sel-sel NK-92 mempamerkan peratus pertumbuhan tertinggi pada 100 µg/mL untuk kesemua sebatian flavonoid (*P < 0.05). Walau bagaimanapun, kenaikan dos melebihi 100 µg/mL telah mengakibatkan pengurangan daripada peratusan pertumbuhan sel tersebut. Menerusi hasil kajian ini, sebatian flavonoid yang mengandungi apigenin, luteolin dan quersetin berupaya mempengaruhi kesan pertumbuhan sel NK-92.

Kata kunci: Apigenin; flavonoid; luteolin; sel pembunuh semulajadi; quersetin 

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*Corresponding author; email: nasirmnor@unisza.edu.my