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Sains Malaysiana 52(9)(2023):
http://doi.org/10.17576/jsm-2023-5209-16
Human
Mesenchymal Stem Cell Derived from Bone Marrow and Umbilical Cord Display
Anti-Cancer Activity in Cancer Cell Lines in vitro
(Sel Stem Mesenkima Manusia Diambil daripada Sum-sum Tulang dan Tali Pusat menunjukkan Aktiviti Anti-Kanser dalam Titisan Sel Kanser secara in vitro)
NOOR ATIQAH
FAKHARUZI, MOON NIAN LIM, ZUHAIRI ABDUL RAHMAN, NURUL AIN NASIM MOHD YUSOF,
EZALIA ESA & KAMAL SHAIK FAKIRUDDIN*
Haematology Unit, Cancer
Research Centre, Institute for Medical Research (IMR), National Institutes of
Health (NIH), Ministry of Health Malaysia (MOH), 40170 Shah Alam, Selangor, Malaysia
Received: 17 October 2022/Accepted: 5 September 2023
Abstract
The anti-tumour efficacy of engineered
mesenchymal stem cell (MSCs) in cancers have been well documented by several
reports. However, the impact of MSCs on the pathogenesis of solid cancers
remains elusive. The study aims to elucidate the role of MSCs from bone marrow
(BMMSCs) and umbilical cord (UCMSCs) on the proliferation, apoptosis and clonogenicity of cancer cell including H2170 (squamous cell
carcinoma), LN18 (glioblastoma) and MCF7 (breast cancer) in vitro.
Highest concentration of conditioned medium derived from the UCMSCs was
significantly (p<0.001) effective to inhibit the proliferation of H2170
(25.8 ± 3.5%), LN18 (17.6 ± 6.5%) and MCF7 (33.2 ± 6.8%) as compared to 100%
viability in basal. Both MSCs and its conditioned medium were able to significantly
(p<0.001) induce apoptosis (early and late) to the H2170 and LN18 cells.
However, for MCF7 cells, co-cultured with both MSCs had higher impact on the
apoptosis as compared to their condition medium. Furthermore,
conditioned medium from UCMSCs were able to significantly reduced the number of
colonies in H2170 (609.5 ± 4.9) and LN18 (171.3 ± 12.6) as compared to control
(H2170; 1196.3 ±12.8 and LN18; 253.3 ± 12.3), suggesting that these two cancer
cells are sensitive to the MSCs. Notably, by
co-culturing of all three cancer cell lines with the MSCs’ conditioned medium, we found that there was an increased expression of
more than two-fold in BAX, BAD, and APAF1 genes showing the ability of MSCs’ conditioned medium to induce the intrinsic apoptosis pathway in the cancer cells. Collectively, our findings demonstrated that the
MSCs could induce apoptosis and inhibit both H2170 and LN18 cancer cell
proliferation. Furthermore, this study did not find evidence of MSCs in
enhancing tumorigenic characteristics of these cancer cells, and thus we
postulate that MSCs are basically safe as a cell-based therapy in cancer
treatment.
Keywords: Anti-cancer; cancer cell lines; in vitro; mesenchymal stem cell
Abstrak
Efikasi
kejuruteraan sel stem mesenkima (MSC) dalam menangani beberapa jenis kanser
telah pun dilaporkan. Namun demikian, impak MSC terhadap patogenesis kanser
pepejal masih kurang diketahui. Kajian ini bertujuan untuk menjelaskan peranan
MSC daripada sum-sum tulang (BMMSC) dan tali pusat (UCMSC) terhadap
pertumbuhan, apoptosis dan fungsi klonogenisiti sel kanser H2170 (karsinoma sel
skuamosa), LN18 (glioblastoma) dan MCF 7 (kanser payudara). Media pertumbuhan
berpekatan tertinggi yang diperoleh daripada UCMSC adalah berkesan (p<0.001) untuk menghalang pertumbuhan sel H2170 (25.8 ± 3.5%), LN18
(17.6 ± 6.5%) dan MCF7 (33.2 ± 6.8%) apabila dibandingkan dengan 100% keviabelan asas.
Kedua-dua BMMSC dan UCMSC serta media pertumbuhan mereka mendorong apoptosis
(peringkat awal dan akhir) bererti (p<0.001) terhadap sel-sel H2170 dan
LN18. Walau bagaimanapun, bagi sel-sel MCF7, pengkulturan bersama kedua-dua MSC
menunjukkan kesan apoptosis yang lebih tinggi berbanding dengan media
pertumbuhan mereka. Selain itu,
media pertumbuhan daripada UCMSC nyata dapat mengurangkan bilangan koloni sel
H2170 (609.5 ± 4.9) dan LN18 (171.3 ± 12.6) berbanding dengan kawalan (H2170;
1196.3 ±12.8 dan LN18; 253.3 ± 12.3), mencadangkan bahawa kedua-dua sel kanser
adalah sensitif terhadap MSC. Secara ketara, kami mendapati bahawa pengkulturan
ketiga-tiga titisan sel kanser tersebut bersama dengan media pertumbuhan MSC
dapat meninggikan lebih dua kali ganda eskpresi gen BAX, BAD dan APAF1,
menunjukkan bahawa media pertumbuhan MSC dapat mendorong laluan apoptosis
intrinsik pada sel kanser tersebut. Secara
keseluruhan, kajian ini telah menunjukkan bahawa MSC dapat mendorong apoptosis
dan menyekat pertumbuhan sel kanser H2170 dan LN18. Di samping itu, kajian ini tidak
menunjukkan bahawa MSC meningkatkan ciri tumorigenik
pada sel kanser, maka kami mempostulatkan bahawa MSC adalah
selamat bagi terapi berasaskan sel bagi rawatan kanser.
Kata kunci:
Anti-kanser; in vitro; sel kanser; sel
stem mesenkima
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*Corresponding
author; email: kamal.shaik@moh.gov.my
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