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Article Open Access

Silymarin induces multiple myeloma cell apoptosis by inhibiting the JAK2/STAT3 signaling pathway

  • Authors:
    • Haiyun Liu
    • Tingting Liu
    • Junquan Zeng
    • Quangang Fang
  • View Affiliations / Copyright

    Affiliations: Department of Clinical Laboratory, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nangchang, Jiangxi 330000, P.R. China, Department of Hematology, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nangchang, Jiangxi 330000, P.R. China, Department of Hematology, The Affiliated Hospital of Jinggangshan University, Ji'an, Jiangxi 343000, P.R. China
    Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 426
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    Published online on: July 4, 2025
       https://doi.org/10.3892/ol.2025.15172
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Abstract

Multiple myeloma (MM) is a malignant tumor that originates in the plasma cells of the bone marrow, interfering with the production of healthy blood cells and causing notable damage to bones and other tissues. Currently, the treatment options for MM are limited and often fail to provide effective and well‑tolerated solutions. Silymarin, a primary active compound found in the dried fruit of Silybum marianum, is known for its inhibitory action on lipoxygenases and peroxidases. In addition to its known benefits in reducing liver toxicity and enhancing radiation protection, silymarin has shown promise in lowering lipid levels. Silymarin has anticancer properties; however, the specific mechanisms and efficacy of silymarin in treating MM require further investigation. In the present study, network pharmacology was employed to discern the targets and associated pathways of silymarin against MM. The cytotoxic effects of silymarin on MM were subsequently tested using RPMI 8226 and H929 cell lines. Furthermore, the molecular targets of silymarin in MM were assessed through immunofluorescence, reverse transcription‑quantitative polymerase chain reaction and molecular docking studies. A total of 15 notable targets of silymarin associated with MM were identified, along with 60 interactions among these targets and several associated signaling pathways. In vitro experiments using Cell Counting Kit‑8 and flow cytometry revealed that silymarin markedly promoted apoptosis in MM cells. Additionally, there was a reduction in the expression of anti‑apoptotic genes, such as Bcl‑2 and Bcl‑xL. After silymarin treatment, a decrease in phosphorylation of JAK2 and STAT3 was observed in MM cells, and it was suggested that silymarin potentially binds to JAK2 and STAT3. In conclusion, silymarin was revealed to trigger apoptosis in MM cells by blocking the JAK2/STAT3 signaling pathway. This mechanism highlights the potential of silymarin as a therapeutic agent that can target specific molecular pathways to combat MM.
View Figures

Figure 1

Analysis of overlapping targets
between silymarin and MM. (A) Overlap of gene targets associated
with both MM and silymarin. The red node represents silymarin, the
blue node represents MM, the yellow nodes represent silymarin
targets and the gray nodes represent MM genes. (B) Protein-protein
interaction network of the shared targets. The color depth of nodes
is directly proportional to the degree of nodes. The darker the
color, the greater the degree of nodes and the lighter the color,
the smaller the degree of nodes. MM, multiple myeloma.

Figure 2

Enrichment analysis of potential
targets of silymarin in multiple myeloma treatment. (A) KEGG
enrichment analysis. Analyses of enriched (B) BP, (C) MF and (D)
CC. The color of the dots is associated with the P-value. The size
of the dots represents the number of genes, and the larger the dots
the more genes there are. KEGG, Kyoto Encyclopedia of Genes and
Genomes; BP, biological processes; MF, molecular functions; CC,
cellular components.

Figure 3

Silymarin induces the apoptosis of MM
cells in vitro. Dose-response curves of silymarin on MM cell
lines, (A) RPMI 8226 and (B) H929, as determined by a Cell Counting
Kit-8 assay. (C and D) Silymarin promoted the apoptosis of RPMI
8226 cells. (E and F) Silymarin promoted the apoptosis of H929
cells. n=3; **P<0.01; ***P<0.001. Error bars indicate
standard deviation. MM, multiple myeloma.

Figure 4

Silymarin inhibits the JAK2/STAT3
signaling pathway in multiple myeloma cells. mRNA expression levels
of (A) Bcl-2 and (B) Bcl-xL in the RPMI 8226 cell line (n=3). mRNA
expression levels of (C) Bcl-2 and (D) Bcl-xL in the H929 cell line
(n=3). Immunofluorescence images of (E) JAK2 and (F) pJAK2. (G)
Semi-quantification of levels of pJAK2 in the RPMI 8226 cell line
(n=4). Immunofluorescence images of (H) STAT3 and (I) pSTAT3.
Semi-quantification of (J) levels of pSTAT3 and (K) nuclear
localization of pSTAT3 in the RPMI 8226 cell line (n=4).
*P<0.05; **P<0.01; ***P<0.001. Error bars indicate
standard deviation. p, phosphorylated; AU, arbitrary units.

Figure 5

Interaction mode between silymarin
and JAK2/STAT3. (A) Docking diagram of silymarin and JAK2 protein.
(B) Docking diagram of silymarin and STAT3 protein. In addition,
the planar structure of silymarin can be seen in the 2D image.
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Liu H, Liu T, Zeng J and Fang Q: Silymarin induces multiple myeloma cell apoptosis by inhibiting the JAK2/STAT3 signaling pathway. Oncol Lett 30: 426, 2025.
APA
Liu, H., Liu, T., Zeng, J., & Fang, Q. (2025). Silymarin induces multiple myeloma cell apoptosis by inhibiting the JAK2/STAT3 signaling pathway. Oncology Letters, 30, 426. https://doi.org/10.3892/ol.2025.15172
MLA
Liu, H., Liu, T., Zeng, J., Fang, Q."Silymarin induces multiple myeloma cell apoptosis by inhibiting the JAK2/STAT3 signaling pathway". Oncology Letters 30.3 (2025): 426.
Chicago
Liu, H., Liu, T., Zeng, J., Fang, Q."Silymarin induces multiple myeloma cell apoptosis by inhibiting the JAK2/STAT3 signaling pathway". Oncology Letters 30, no. 3 (2025): 426. https://doi.org/10.3892/ol.2025.15172
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Spandidos Publications style
Liu H, Liu T, Zeng J and Fang Q: Silymarin induces multiple myeloma cell apoptosis by inhibiting the JAK2/STAT3 signaling pathway. Oncol Lett 30: 426, 2025.
APA
Liu, H., Liu, T., Zeng, J., & Fang, Q. (2025). Silymarin induces multiple myeloma cell apoptosis by inhibiting the JAK2/STAT3 signaling pathway. Oncology Letters, 30, 426. https://doi.org/10.3892/ol.2025.15172
MLA
Liu, H., Liu, T., Zeng, J., Fang, Q."Silymarin induces multiple myeloma cell apoptosis by inhibiting the JAK2/STAT3 signaling pathway". Oncology Letters 30.3 (2025): 426.
Chicago
Liu, H., Liu, T., Zeng, J., Fang, Q."Silymarin induces multiple myeloma cell apoptosis by inhibiting the JAK2/STAT3 signaling pathway". Oncology Letters 30, no. 3 (2025): 426. https://doi.org/10.3892/ol.2025.15172
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