Sains Malaysiana 47(6)(2018): 1209–1219

http://dx.doi.org/10.17576/jsm-2018-4706-16

The Potential of Neural Stem Cell as Vehicle to Deliver Quercus infectoria Extract to Glioma Cell In Vitro

(Peranan Sel Stem Neuron sebagai Pembawa Ekstrak Quercus infectoria ke Sel Glioma in vitro)

TAN SUAT CHENG*, LOHIS BALACHANDRAN, NORHAZILAH MOHAMAD, KANG IN NEE,  AMIRUL NASARUDIN, RUZI AINI ZAKARIA & HASMAH ABDULLAH

Biomedicine Programme, School of Health Sciences, Universiti Sains Malaysia

11800 Gelugor, Penang, Malaysia

Received: 1 October 2017/Accepted: 5 February 2018

ABSTRACT

Glioblastoma multiforme (GBM) is the most malignant subtype of brain cancer. However, current clinical treatments for GBM are limited in effectiveness and often impose additional side effects on patients. Here, we developed targeted anti-cancer therapy (TAT) using neural stem cells (NSC) as delivery agent to transport anti-cancer compounds directly to GBM in vitro. Anti-cancer active compounds: Tannic acid (TA) and gallic acid (GA) were extracted from local medicinal plant - Quercus infectoria (QI) using soxhlet technique with 100% methanol (QI-100%) or 70% methanol (QI-70%) solvent. Concentration of TA and GA measured using HPLC were 72.56 and 43.66 μg/mL in QI-100%, while in QI-70%, the concentrations were 72.41 and 43.31 μg/mL, respectively. Cytotoxicity effects of QI-100% and QI-70% on human GBM cell line (DBTRG-05MG), human NSC line (H9-hNSC) and human normal brain glial cell line (SVG-p12) (as negative control) were determined using MTT assay. Both QI-100% and QI-70% showed anti-proliferative properties against DBTRG-05MG at IC50, but not on H9-hNSC and SVG-p12. Taken together, data indicated that both QI extracts contained TA and GA which exhibit anti-proliferative effect specifically on cancerous cells only. Next, QI-treated H9-hNSC was seeded in a modified Boyden chamber for 12 h to investigate its migration capacity towards DBTRG-05MG. The result showed that H9-hNSC migrated towards DBTRG-05MG with 4-folds higher capacity compared to control. In addition, the migration of QI-100% treated H9-hNSC successfully reduced the number of DBTRG-05MG, indicating the anti-GBM potential of these cells after migration. In conclusion, NSC could be a specific anti-cancer compound delivery agent for GBM, reducing unwanted side effects on patients.

Keywords: Glioblastoma multiforme (GBM); neural stem cells (NSC); Quercus infectoria (QI); targeted anti-cancer therapy (TAT)

ABSTRAK

Glioblastoma multiforme (GBM) adalah sub-jenis kanser otak yang paling berbahaya. Rawatan klinikal pada masa kini adalah terhad daripada segi keberkesanan serta boleh mengakibatkan kesan sampingan pada pesakit. Kajian ini meneliti rawatan bersasarkan kanser (TAT) dengan menggunakan sel stem neuron (NSC) sebagai pembawa sebatian anti-kanser ke sel sasaran GBM. Sebatian anti-kanser: Asid tanik (TA) dan asid galik (GA) diekstrak daripada tumbuhan perubatan tempatan - Quercus infectoria (QI) dengan menggunakan 100% (QI-100%) dan 70% (QI-70%) metanol melalui teknik soxhlet. Kepekatan TA dan GA hasilan ujian HPLC adalah 72.56 dan 43.66 μg/mL dalam QI-100%, manakala dalam QI-70% adalah 72.41 dan 43.31 μg/mL. Kesan sitotoksisiti QI-100% dan QI-70% terhadap sel GBM manusia (DBTRG- 05MG), sel NSC manusia (H9-hNSC) dan sel glial otak manusia (SVG-p12) dikaji dengan asai MTT. Kedua-dua QI-100% dan QI-70% menunjukkan perencatan populasi sel DBTRG-05MG pada IC50, tetapi tidak merencatkan populasi sel H9- hNSC dan SVG-p12. Data terkumpul menunjukkan bahawa estrak QI mengandungi sebatian TA dan GA yang mempunyai aktiviti perencatan spesifik terhadap sel kanser sahaja. Seterusnya, H9-hNSC yang telah dirawat dengan QI dimasukkan dalam kebuk Boyden terubah suai selam 12 jam untuk tujuan kajian kapasiti migrasi H9-hNSC ke DBTRG-05MG. Data menunjukkan kapasiti migrasi H9-hNSC ke DBTRG-05MG adalah 4 kali ganda lebih tinggi daripada sampel kawalan. Selain itu, migrasi H9-hNSC yang telah dirawat dengan QI-100% berupaya untuk mengurangkan bilangan sel-sel DBTRG- 05MG. Ini membuktikan potensi anti-GBM sel berkenaan selepas migrasi. Kesimpulannya, NSC boleh digunakan sebagai agen pembawa sebatian anti-kanser dalam rawatan GBM untuk mengurangkan kesan sampingan terhadap pesakit.

Kata kunci: Glioblastoma multiforme (GBM); Quercus infectoria (QI); rawatan bersasarkan kanser (TAT); sel stem neuron (NSC)

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*Corresponding author; email: tansc@usm.my