Typhonium flagelliforme extract induce apoptosis in breast cancer stem cells by suppressing survivin
Agung Putra1, Ignatius Riwanto2, Suhartono Taat Putra3
1Biomedical Science Doctoral Program, Medical Faculty, Diponegoro University; Stem Cell and Cancer Research Laboratory, Medical Faculty, Sultan Agung Islamic University, Semarang, Indonesia.
Context:
Breast cancer stem cells (bCSCs) are a small population of cancer-initiating cells within breast cancer, characterized as CD44+ CD24-/low. bCSCs develop apoptosis resistance by expressing survivin and suppressing caspase-9 and caspase-3 expression. Typhonium flagelliforme tuber extract (TFTe) can induce apoptosis in several types of cancer cells; however, the effects of TFTe to induce the bCSCs remain unclear.
Aims:
This study aimed to investigate the effects of TFTe on apoptosis induction in bCSCs through the suppression of survivin and the exhibition of caspase-9 and caspase-3.
Settings And Design:
This study employed a posttest only, control group design.
Subjects And Methods:
To analyze the apoptotic index, TFTe, at concentrations of 25 (Tf1d), 50.89 (Tf2d), and 100 μg/mL (Tf3d) were used to treat bCSCs for 24 h, in a humidified incubator containing 5% CO2, at 37°C. The control group was exposed to dimethyl sulfoxide. Apoptosis was measured by propidium iodide and acridine orange double-staining, and the expression levels of survivin, caspase-9, and caspase-3 were assessed by immunocytochemistry.
Statistical Analysis Used:
Differences were analyzed by the independent Student's t-test, to compare two groups, and the Kruskal-Wallis test, to compare more than two groups. P < 0.05 was considered statistically significant.
Results:
TFTe inhibited bCSC proliferation, with an IC50 value of 50.89 μg/mL, and significantly induced apoptosis in bCSCs (P < 0.001). TFTe also significantly decreased the expression levels of survivin in bCSCs (P < 0.001) and increased the expression levels of caspase-9 and caspase-3 (P < 0.001).
Conclusions:
TFTe can induce apoptosis in bCSCs by decreasing survivin expression levels and increasing the levels of caspase-9 and caspase-3.
Insights
Typhonium flagelliforme tuber extract (TFTe) effectively induces apoptosis in breast cancer stem cells (bCSCs). TFTe achieves this by reducing survivin and increasing caspase-9 and caspase-3 levels, offering a potential therapeutic strategy.
Area of Science:
- Oncology
- Cell Biology
- Pharmacology
Background:
- Breast cancer stem cells (bCSCs) are CD44+ CD24-/low cells driving tumor initiation and exhibiting resistance to apoptosis via survivin.
- bCSCs suppress key apoptotic proteins like caspase-9 and caspase-3, contributing to treatment resistance.
- Typhonium flagelliforme tuber extract (TFTe) shows promise in inducing apoptosis in various cancer cells, but its effect on bCSCs is unexplored.
Purpose of the Study:
- To investigate the efficacy of TFTe in inducing apoptosis in bCSCs.
- To determine if TFTe modulates survivin expression and caspase-9 and caspase-3 activity in bCSCs.
Main Methods:
- A controlled experimental design was used to treat bCSCs with varying concentrations of TFTe (25, 50.89, 100 μg/mL).
- Apoptosis was quantified using propidium iodide and acridine orange double-staining.
- Survivin, caspase-9, and caspase-3 expression levels were assessed via immunocytochemistry.
Main Results:
- TFTe demonstrated significant inhibition of bCSC proliferation with an IC50 of 50.89 μg/mL.
- TFTe treatment led to a statistically significant induction of apoptosis in bCSCs (P < 0.001).
- TFTe significantly decreased survivin expression and significantly increased caspase-9 and caspase-3 expression in bCSCs (P < 0.001).
Conclusions:
- TFTe effectively induces apoptosis in breast cancer stem cells.
- The mechanism involves the downregulation of survivin and the upregulation of caspase-9 and caspase-3.
- TFTe presents a potential therapeutic agent for targeting bCSCs in breast cancer treatment.
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