ArticleInternational journal of oncology2015
Shikonin, dually functions as a proteasome inhibitor and a necroptosis inducer in multiple myeloma cells.
Article in International journal of oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 72 citations in OpenAlex.
- Targeting the proteasome in cancer therapy: development and future opportunities in natural products.Frontiers in pharmacology · 2026Review
- Trigger Points of Necroptosis (RIPK1, RIPK3, and MLKL)-Promising Horizon or Blind Alley in Therapy of Colorectal Cancer?International journal of molecular sciences · 2025Review
- Screening of an FDA-Approved Drug Library: Menadione Induces Multiple Forms of Programmed Cell Death in Colorectal Cancer Cells via MAPK8 Cascades.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Label-free fluorescence lifetime imaging for the assessment of cell viability in living tumor fragments.Journal of biomedical optics · 2024Article
- Exploring natural killer cell-related biomarkers in multiple myeloma: a novel nature killer cell-related model predicting prognosis and immunotherapy response using single-cell study.Clinical and experimental medicine · 2024Article
- Anoikis and cancer cell differentiation: novel modes of shikonin derivatives anticancer action in vitro.Molecular biology reports · 2024Article
- Synthetic Small Molecule Modulators of Hsp70 and Hsp40 Chaperones as Promising Anticancer Agents.International journal of molecular sciences · 2023Review
- The anti-leukemia activity and mechanisms of shikonin: a mini review.Frontiers in pharmacology · 2023Review
- Necroptosis: A Pathogenic Negotiator in Human Diseases.International journal of molecular sciences · 2022Review
- Mechanism of Bile Acid-Induced Programmed Cell Death and Drug Discovery against Cancer: A Review.International journal of molecular sciences · 2022Review
- Systematic Screening of Chemical Constituents in the Traditional Chinese MedicineMolecules (Basel, Switzerland) · 2022Article
- Article
- Shikonin induces ferroptosis in multiple myelomaFrontiers in oncology · 2022Article
- Molecular mechanism of shikonin inhibiting tumor growth and potential application in cancer treatment.Toxicology research · 2021Article
- Targeting Drug Chemo-Resistance in Cancer Using Natural Products.Biomedicines · 2021Review
- Review
- Shikonin reduces hepatic fibrosis by inducing apoptosis and inhibiting autophagy via the platelet-activating factor-mitogen-activated protein kinase axis.Experimental and therapeutic medicine · 2021Article
- Natural product scaffolds as inspiration for the design and synthesis of 20S human proteasome inhibitors.RSC chemical biology · 2020Article
- The Role of Necroptosis in ROS-Mediated Cancer Therapies and Its Promising Applications.Cancers · 2020Review
- Shikonin induces colorectal carcinoma cells apoptosis and autophagy by targeting galectin-1/JNK signaling axis.International journal of biological sciences · 2020Article
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Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Shikonin (SHK), a natural small agent (MW 288.3), reportedly induces cell death in various tumor cells. We have found that SHK also exerts potent cytocidal effects on human multiple myeloma (MM) cells, but its anticancer mechanism in MM cells remains to be elucidated. SHK at 2.5-5 µM induced apoptosis in seven MM cell lines, including the bortezomib-resistant cell line KMS11/BTZ. The IC50 value of SHK against KMS11/BTZ was comparable to that of a parental cell line KMS11 (1.1 and 1.56 µM, respectively). SHK induces accumulation of ubiquitinated proteins and activates XBP-1 in MM cells, suggesting that SHK functions as a proteasome inhibitor, eventually inducing ER stress-associated apoptosis. SHK increases levels of HSP70/72, which protects cells from apoptosis, and exerts greater cytocidal effects in combination with the HSP70/72 inhibitor VER-155008. At higher concentrations (10-20 µM), SHK induced cell death, which was completely inhibited by a necroptosis inhibitor, necrostatin-1 (Nec-1), while the cytocidal activity was unaffected by Z-VAD-FMK, strongly suggesting that cell death is induced by SHK at high concentrations through necroptosis. The present data show for the first time that SHK induces cell death in MM cells. SHK efficiently induces apoptosis and combination of heat shock protein inhibitor with low dose SHK enhances apoptosis, while high dose SHK induces necroptosis in MM cells. These findings together support the use of SHK as a potential therapeutic agent for MM.
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