1.Advancing towards Effective Glioma Therapy: MicroRNA Derived from Umbilical Cord Mesenchymal Stem Cells’ Extracellular Vesicles
Eko Ngadiono ; Novi Silvia Hardiany
Malaysian Journal of Medical Sciences 2019;26(4):5-16
A glioma, especially a grade IV glioblastoma, is a malignant tumour with a poor prognosis
despite growing medical advancements. Researchers have been looking for better and more
effective treatments targeting the molecular pathways of gliomas due to glioblastomas’ ability
to develop resistance to chemotherapies. Moreover, glioma stem cells (GSC) contribute to
maintaining the glioma population, which benefits from its ability to self-renew and differentiate.
Recent research has reported that through the introduction of umbilical cord mesenchymal
stem cells (UCMSC) into glioma cells, the growth and development of the glioma cells can be
downregulated. It has more currently been found out that UCMSC release extracellular vesicles
(EVs) containing miRNA that are responsible for this phenomenon. Therefore, this review analyses
literature to discuss all possible miRNAs contained within the UCMSC’s EVs and to elaborate on
their molecular mechanisms in halting gliomas and GSC growth. This review will also include the
challenges and limitations, to account for which more in vivo research is suggested. In conclusion,
this review highlights how miRNAs contained within UCMSC’s EVs are able to downregulate
multiple prominent pathways in the survival of gliomas.
2.Reactive Oxygen Species (ROS) in Cancer and Cancer Stem Cells Spesies Oksigen Reaktif (ROS) dalam Kanser dan Kanser Stem Sel (CSC)
FEBRIAL HIKMAH ; NOVI SILVIA HARDIANY
Malaysian Journal of Health Sciences 2021;19(No.2):35-41
Reactive Oxygen Species (ROS) are aerobic metabolic byproducts, mainly produced by mitochondria. Most types of
cancer contain high amounts of ROS. An increase in endogenous ROS triggers adaptive changes, induces oxidative stress
and cytotoxic. Oxidative stress can lead to cancer. But on the other hand, the radiotherapy treatment method induces the
formation of ROS in the process of cell death. Resistance therapy in cancer cells is associated with high antioxidant
enzymes that neutralize ROS in cancer cells. In addition, therapeutic resistance and recurrence are also associated with
the presence of cancer stem cells (CSCs). Several studies have shown that ROS levels are found to be low in CSCs. Low
levels of ROS are likely to play a role in the survival of CSCs. Therefore, modulation of ROS levels in CSCs can be used
as an alternative therapy.
3.Gene Expression of Molecules Regulating Apoptotic Pathways in Glioblastoma Multiforme Treated with Umbilical Cord Stem Cell Conditioned Medium
Novi Silvia Hardiany ; Edward Christopher Yo ; Eko Ngadiono ; Septelia Inawati Wanandi
Malaysian Journal of Medical Sciences 2019;26(6):35-45
Background: Glioblastoma multiforme (GBM) is the most malignant primary brain
tumour and there is no definite cure. It has been suggested that there are significant interactions
among mesenchymal stem cells (MSCs), their released factors and tumour cells that ultimately
determine GBM’s growth pattern. This study aims to analyse the expression of molecules involved
in GBM cell apoptotic pathways following treatment with the MSC secretome.
Methods: A conditioned medium of umbilical cord-derived MSCs (UCMSC-CM) was
generated by culturing the cells on serum-free αMEM for 24 h. Following this, human GBM T98G
cells were treated with UCMSC-CM for 24 h. Quantitative reverse transcriptase-polymerase chain
reaction (qRT-PCR) was then performed to measure the mRNA expression of survivin, caspase-9,
TNF-related apoptosis-inducing ligand (TRAIL), DR4 and DcR1.
Results: mRNA expression of caspase-9 in CM-treated T98G cells increased 1.6-fold
(P = 0.017), whereas mRNA expression of survivin increased 3.5-fold (P = 0.002). On the other
hand, TRAIL protein expression was upregulated (1.2-fold), whereas mRNA expression was
downregulated (0.4-fold), in CM-treated cells. Moreover, there was an increase in the mRNA
expression of both DR4 (3.5-fold) and DcR1 (1,368.5-fold) in CM-treated cells.
Conclusion: The UCMSC-CM was able to regulate the expression of molecules involved
in GBM cell apoptotic pathways. However, the expression of anti-apoptotic molecules was more
upregulated than that of pro-apoptotic molecules.
4.Profiling of Gene Expression Associated with Stemness and Aggressiveness of ALDH1A1- Expressing Human Breast Cancer Cells
Septelia Inawati Wanandi ; Resda Akhra Syahrani ; Sekar Arumsari ; Gita Wideani ; Novi Silvia Hardiany
Malaysian Journal of Medical Sciences 2019;26(5):38-52
Background: It has been widely reported that breast cancer aggressiveness may be driven
by breast cancer stem cells (BCSCs). BCSCs display stemness properties that include self-renewal,
tumourigenicity and pluripotency. The regulation of gene expression may have important roles in
BCSC stemness and aggressiveness. Thus, the aim of this study was to examine the stemness and
aggressiveness gene expression profile of BCSCs compared to MCF-7 and MDA-MB-231 breast
cancer cells.
Methods: Human ALDH1+ BCSCs were grown in serum-free Dulbecco’s Modified Eagle
Medium (DMEM)/F12, while MCF-7 and MDA-MB-231 were cultured in DMEM supplemented with
10% foetal bovine serum under standard conditions. Total RNA was extracted using the Tripure
Isolation Reagent. The relative mRNA expressions of OCT4, ALDH1A1 and CD44 associated with
stemness as well as TGF-β1, TβR1, ERα1 and MnSOD associated with aggressiveness in BCSCs and
MCF-7 cells were determined using the quantitative real-time PCR (qRT-PCR).
Results: The mRNA expressions of OCT4 (5.19-fold ± 0.338; P = 0.001), ALDH1A1 (3.67-
fold ± 0.523; P = 0.006), CD44 (2.65-fold ± 0.307; P = 0.006), TGF-β1 (22.89-fold ± 6.840; P =
0.015), TβR1 (3.74-fold ± 1.446; P = 0.045) and MnSOD (4.6-fold ± 1.096; P = 0.014) were higher
in BCSCs than in MCF-7 but were almost similar to MDA-MB-231 cells. In contrast, the ERα1
expression of BCSCs (0.97-fold ± 0.080; P = 0.392) was similar to MCF-7 cells, indicating that
BSCSs are oestrogen-dependent breast cancer cells.
Conclusion: The oestrogen-dependent BCSCs express stemness and aggressiveness genes
at a higher level compared to oestrogen-dependent MCF-7 but are almost similar to oestrogenindependent
MDA-MB-231 cells.