ArticleBiomolecules & therapeutics2019
Shikonin Exerts Cytotoxic Effects in Human Colon Cancers by Inducing Apoptotic Cell Death via the Endoplasmic Reticulum and Mitochondria-Mediated Pathways.
Article in Biomolecules & therapeutics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 42 citations in OpenAlex.
- New Paradigm for Rheumatoid Arthritis Treatment: A Review of 'Crosstalk' Mechanism of Multi-Targeted Intervention on Cytokine/Chemokine Networks by Chinese Medicine.Chinese journal of integrative medicine · 2026Review
- Systematic characterization of the R2R3-MYB family in Lithospermum erythrorhizon and regulatory mechanisms of LeMYB1 in shikonin biosynthesis.BMC plant biology · 2026Article
- Piperine alleviates retinal ischemic injury by mediating the APE1 signaling.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Evaluation of Bacillus sp. strain isolated from pesticide influenced rhizospheric soil for dimethoate degrading potential.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2025Article
- Investigating the Role of Shikonin in Enhancing Osteogenesis and Angiogenesis for the Treatment of Osteoporosis.ACS omega · 2025Article
- Effect and mechanisms of shikonin on breast cancer cells in vitro and in vivo.BMC complementary medicine and therapies · 2024Article
- Pharmacological Significance ofFoods (Basel, Switzerland) · 2024Review
- Natural products targeting the MAPK-signaling pathway in cancer: overview.Journal of cancer research and clinical oncology · 2024Review
- Systematic bioinformatics analysis reveals the role of shikonin in blocking colon cancer progression by identifying senescence-induced genes.Frontiers in pharmacology · 2024Article
- The anti-leukemia activity and mechanisms of shikonin: a mini review.Frontiers in pharmacology · 2023Review
- Transformation of theranostic alginate-based microbubbles from raspberry-like to core-shell-like microbubbles andRSC advances · 2022Article
- Pharmacological and analytical aspects of alkannin/shikonin and their derivatives: An update from 2008 to 2022.Chinese herbal medicines · 2022Review
- The Endoplasmic Reticulum Stress Response Mediates Shikonin-Induced Apoptosis of 5-Fluorouracil-Resistant Colorectal Cancer Cells.Biomolecules & therapeutics · 2022Article
- Selenium Deficiency Leads to Inflammation, Autophagy, Endoplasmic Reticulum Stress, Apoptosis and Contraction AbnormalitiesFrontiers in immunology · 2022Article
- Application of RNA processing factors for predicting clinical outcomes in colon cancer.Frontiers in genetics · 2022Article
- Shikonin suppresses colon cancer cell growth and exerts synergistic effects by regulating ADAM17 and the IL‑6/STAT3 signaling pathway.International journal of oncology · 2021Article
- Systematic analysis of the function and prognostic value of RNA binding proteins in Colon Adenocarcinoma.Journal of Cancer · 2021Article
- COVID-19 and Parkinson's Disease: Shared Inflammatory Pathways Under Oxidative Stress.Brain sciences · 2020Article
- Melatonin sensitises shikonin-induced cancer cell death mediated by oxidative stress via inhibition of the SIRT3/SOD2-AKT pathway.Redox biology · 2020Article
- TSPYL5 activates endoplasmic reticulum stress to inhibit cell proliferation, migration and invasion in colorectal cancer.Oncology reports · 2020Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The apoptotic effects of shikonin (5,8-dihydroxy-2-[(1R)-1-hydroxy-4-methylpent-3-enyl]naphthalene-1,4-dione) on the human colon cancer cell line SNU-407 were investigated in this study. Shikonin showed dose-dependent cytotoxic activity against SNU-407 cells, with an estimated IC₅₀ value of 3 µM after 48 h of treatment. Shikonin induced apoptosis, as evidenced by apoptotic body formation, sub-G₁ phase cells, and DNA fragmentation. Shikonin induced apoptotic cell death by activating mitogen-activated protein kinase family members, and the apoptotic process was mediated by the activation of endoplasmic reticulum (ER) stress, leading to activation of the PERK/elF2α/CHOP apoptotic pathway, and mitochondrial Ca²⁺ accumulation. Shikonin increased mitochondrial membrane depolarization and altered the levels of apoptosis-related proteins, with a decrease in B cell lymphoma (Bcl)-2 and an increase in Bcl-2-associated X protein, and subsequently, increased expression of cleaved forms of caspase-9 and -3. Taken together, we suggest that these mechanisms, including MAPK signaling and the ER-and mitochondria-mediated pathways, may underlie shikonin-induced apoptosis related to its anticancer effect.
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