Shikonin Promotes Apoptosis in Multiple Myeloma Cells Through the PKM2-AMPK-PGC1α Metabolic Axis.
4 affiliations
- 1Department of Hematology, Tianjin Medical University General Hospital, Tianjin, China.
- 2Tianjin Key Laboratory of Bone Marrow Failure and Malignant Hemopoietic Clone Control, Tianjin, China.
- 3Tianjin Institute of Hematology, Tianjin, China.
- 4College of Science and Technology, Hebei Agricultural University, Baoding, China.
Abstract
Background
Multiple myeloma (MM) is an incurable plasma malignancy. Pyruvate kinase M2 (PKM2), a rate-limiting enzyme in glycolysis, is involved in the metabolic reprogramming of tumors. Shikonin, a natural compound, exhibits anticancer potential. However, whether modulating PKM2 with shikonin can be used as an adjuvant chemotherapeutic strategy for MM remains to be elucidated. We explored the effects of shikonin on the metabolic pathways in MM cells.Methods
Apoptosis, reactive oxygen species (ROS) production, and cell cycle progression in MM cells treated with shikonin were analyzed using flow cytometry. Shikonin-treated MM cells were sent for Metabolomics by RNA sequencing and LC-MS/MS metabolomics. The involved signaling pathways were validated using western blotting.Results
The coMMpass cohort analysis has indicated that high PKM2 expression was related to poor survival of MM cells. Shikonin induced dose-dependently apoptosis, elevated ROS levels, and cell cycle arrest in G1 phase in MM cells. Multi-omics analysis revealed 2043 differentially expressed genes and 93 altered metabolites in shikonin-treated MM cells. Shikonin downregulated the expression of PKM2 and therefore reduced pyruvate/AMP levels and impaired glycolysis. Integrated omics analysis identified AMPK signaling as the common enriched pathway. WB confirmed that shikonin suppressed the expression of PKM2 and GLUT4 and activated the expression of P-AMPK/PGC1α, indicating the dysregulation of the PKM2-AMPK-PGC1α axis.Conclusion
Shikonin exerts anti-tumor effects in MM cells by inhibiting PKM2 expression, disrupting glycolytic flux, activating AMPK/PGC1α-mediated metabolic stress, and triggering the apoptosis process. Inhibition of PKM2 with shikonin is a promising metabolic intervention strategy for MM treatment.
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BibTeX
@article{peng2026shikonin,
title = {{Shikonin Promotes Apoptosis in Multiple Myeloma Cells Through the PKM2-AMPK-PGC1α Metabolic Axis.}},
author = {Fengping Peng and Yu Gao and Ziqi Zhang and Ling Deng and Honglei Liu and Xiaowei Liang and Chunyan Liu and Rong Fu},
journal = {Journal of clinical laboratory analysis},
year = {2026},
month = oct,
doi = {10.1002/jcla.70384},
url = {https://europepmc.org/article/MED/42902814},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Shikonin Promotes Apoptosis in Multiple Myeloma Cells Through the PKM2-AMPK-PGC1α Metabolic Axis.
AU - Fengping Peng
AU - Yu Gao
AU - Ziqi Zhang
AU - Ling Deng
AU - Honglei Liu
AU - Xiaowei Liang
AU - Chunyan Liu
AU - Rong Fu
PY - 2026
DA - 2026/10/20
JO - Journal of clinical laboratory analysis
DO - 10.1002/jcla.70384
UR - https://europepmc.org/article/MED/42902814
AB - Background Multiple myeloma (MM) is an incurable plasma malignancy. Pyruvate kinase M2 (PKM2), a rate-limiting enzyme in glycolysis, is involved in the metabolic reprogramming of tumors. Shikonin, a natural compound, exhibits anticancer potential. However, whether modulating PKM2 with shikonin can be used as an adjuvant chemotherapeutic strategy for MM remains to be elucidated. We explored the effects of shikonin on the metabolic pathways in MM cells.Methods Apoptosis, reactive oxygen species (ROS) production, and cell cycle progression in MM cells treated with shikonin were analyzed using flow cytometry. Shikonin-treated MM cells were sent for Metabolomics by RNA sequencing and LC-MS/MS metabolomics. The involved signaling pathways were validated using western blotting.Results The coMMpass cohort analysis has indicated that high PKM2 expression was related to poor survival of MM cells. Shikonin induced dose-dependently apoptosis, elevated ROS levels, and cell cycle arrest in G1 phase in MM cells. Multi-omics analysis revealed 2043 differentially expressed genes and 93 altered metabolites in shikonin-treated MM cells. Shikonin downregulated the expression of PKM2 and therefore reduced pyruvate/AMP levels and impaired glycolysis. Integrated omics analysis identified AMPK signaling as the common enriched pathway. WB confirmed that shikonin suppressed the expression of PKM2 and GLUT4 and activated the expression of P-AMPK/PGC1α, indicating the dysregulation of the PKM2-AMPK-PGC1α axis.Conclusion Shikonin exerts anti-tumor effects in MM cells by inhibiting PKM2 expression, disrupting glycolytic flux, activating AMPK/PGC1α-mediated metabolic stress, and triggering the apoptosis process. Inhibition of PKM2 with shikonin is a promising metabolic intervention strategy for MM treatment.
SN - 0887-8013
SN - 1098-2825
ER -