{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T06:49:30Z","timestamp":1792565370604,"version":"4.5.0"},"reference-count":43,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:00:00Z","timestamp":1792454400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:00:00Z","timestamp":1792454400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Laboratory Analysis"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Multiple myeloma (MM) is an incurable plasma malignancy. Pyruvate kinase M2 (PKM2), a rate\u2010limiting 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Apoptosis, reactive oxygen species (ROS) production, and cell cycle progression in MM cells treated with shikonin were analyzed using flow cytometry. Shikonin\u2010treated MM cells were sent for Metabolomics by RNA sequencing and LC\u2013MS\/MS metabolomics. The involved signaling pathways were validated using western blotting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The coMMpass cohort analysis has indicated that high PKM2 expression was related to poor survival of MM cells. Shikonin induced dose\u2010dependently apoptosis, elevated ROS levels, and cell cycle arrest in G1 phase in MM cells. Multi\u2010omics analysis revealed 2043 differentially expressed genes and 93 altered metabolites in shikonin\u2010treated 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\u2010AMPK\/PGC1\u03b1, indicating the dysregulation of the PKM2\u2010AMPK\u2010PGC1\u03b1 axis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Shikonin exerts anti\u2010tumor effects in MM cells by inhibiting PKM2 expression, disrupting glycolytic flux, activating AMPK\/PGC1\u03b1\u2010mediated metabolic stress, and triggering the apoptosis process. Inhibition of PKM2 with shikonin is a promising metabolic intervention strategy for MM treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcla.70384","type":"journal-article","created":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T06:36:10Z","timestamp":1792564570000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Shikonin Promotes Apoptosis in Multiple Myeloma Cells Through the\n                    <scp>PKM2<\/scp>\n                    \u2010\n                    <scp>AMPK<\/scp>\n                    \u2010\n                    <scp>PGC1\u03b1<\/scp>\n                    Metabolic Axis"],"prefix":"10.1002","author":[{"given":"Fengping","family":"Peng","sequence":"first","affiliation":[{"name":"Department of Hematology Tianjin Medical University General Hospital  Tianjin China"},{"name":"Tianjin Key Laboratory of Bone Marrow Failure and Malignant Hemopoietic Clone Control  Tianjin 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