Human Umbilical Cord-Mesenchymal Stem Cells (UC-MSCs) Lysate Suppresses The Growth Of Cervical Cancer (HeLa Cells) In Vitro

Introduction: Mesenchymal stem cells (MSCs), especially those derived from the umbilical cord (UC-MSCs), have emerged as promising candidates for cancer therapy due to their immunomodulatory and anti-tumour properties. However, the mechanisms through which UC-MSCs affect cervical cancer cells remain unclear. This study aimed to investigate the effects of UC-MSCs on HeLa cervical cancer cells, focusing on cytoskeletal alterations and apoptosis-related pathways. Methods: HeLa cells were co-cultured with UC-MSCs at varying concentrations (5%, 10%, 20%, and 30%). Doxorubicin (3 ppm) was used as a positive control, and untreated HeLa cells served as the negative control. Apoptosis markers (caspase-3 and caspase-8) were analysed using immunocytochemistry (ICC), while DAPI/phalloidin staining was used to observe cytoskeletal changes. Levels of cytokines (CCL2 and TGF-α) were measured using ELISA. Results: Activation of caspase-3 was observed at 5% UC-MSC concentration, indicating the induction of apoptosis. However, higher UC-MSC concentrations (10–30%) led to a decrease in HeLa cell viability without caspase-3 or caspase-8 activation, suggesting alternative cell death pathways such as necrosis or autophagy. No caspase-8 activation was observed across all treatments, indicating resistance to extrinsic apoptosis, possibly due to the expression of anti-apoptotic proteins like c-FLIP. ELISA analysis showed no significant changes in CCL2 and TGF-α levels. Conclusion: UC-MSCs can induce HeLa cell death via caspase-independent mechanisms, particularly at higher concentrations. The selective activation of caspase-3 at low concentrations highlights the complex interaction between UC-MSCs and cervical cancer cells. These findings contribute to a deeper understanding of MSC-based cancer therapy and offer insights for the development of novel therapeutic strategies.

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Publication Details

Journal
Bali Medical Journal
Published
2025-08-28
DOI
https://doi.org/10.15562/bmj.v14i2.5689
Primary Topic
Mesenchymal stem cell research
Type
article
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article

Human Umbilical Cord-Mesenchymal Stem Cells (UC-MSCs) Lysate Suppresses The Growth Of Cervical Cancer (HeLa Cells) In Vitro

Aida Ariyanti, Afrinda Dwi Wahyuni, Deya Karsari, Andang Miatmoko et al.
Bali Medical Journal
Mesenchymal stem cell research
article

Human Umbilical Cord-Mesenchymal Stem Cells (UC-MSCs) Lysate Suppresses The Growth Of Cervical Cancer (HeLa Cells) In Vitro

Aida Ariyanti, Afrinda Dwi Wahyuni, Deya Karsari, Andang Miatmoko, Nora Ertanti, Eryk Hendrianto, Aristika Dinaryanti, Purwati Purwati, Asa Ardiana, Fajar Wira Dwiputra
article en

Abstract

Introduction: Mesenchymal stem cells (MSCs), especially those derived from the umbilical cord (UC-MSCs), have emerged as promising candidates for cancer therapy due to their immunomodulatory and anti-tumour properties. However, the mechanisms through which UC-MSCs affect cervical cancer cells remain unclear. This study aimed to investigate the effects of UC-MSCs on HeLa cervical cancer cells, focusing on cytoskeletal alterations and apoptosis-related pathways. Methods: HeLa cells were co-cultured with UC-MSCs at varying concentrations (5%, 10%, 20%, and 30%). Doxorubicin (3 ppm) was used as a positive control, and untreated HeLa cells served as the negative control. Apoptosis markers (caspase-3 and caspase-8) were analysed using immunocytochemistry (ICC), while DAPI/phalloidin staining was used to observe cytoskeletal changes. Levels of cytokines (CCL2 and TGF-α) were measured using ELISA. Results: Activation of caspase-3 was observed at 5% UC-MSC concentration, indicating the induction of apoptosis. However, higher UC-MSC concentrations (10–30%) led to a decrease in HeLa cell viability without caspase-3 or caspase-8 activation, suggesting alternative cell death pathways such as necrosis or autophagy. No caspase-8 activation was observed across all treatments, indicating resistance to extrinsic apoptosis, possibly due to the expression of anti-apoptotic proteins like c-FLIP. ELISA analysis showed no significant changes in CCL2 and TGF-α levels. Conclusion: UC-MSCs can induce HeLa cell death via caspase-independent mechanisms, particularly at higher concentrations. The selective activation of caspase-3 at low concentrations highlights the complex interaction between UC-MSCs and cervical cancer cells. These findings contribute to a deeper understanding of MSC-based cancer therapy and offer insights for the development of novel therapeutic strategies.

Bali Medical JournalVol. 14(2)
Openalex Percentile: Top 61%
Mesenchymal stem cell research
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