ArticleAutophagy2013
Energy deprivation by silibinin in colorectal cancer cells: a double-edged sword targeting both apoptotic and autophagic machineries.
Article in Autophagy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
35 citing papers in PubMed, 74 citations in OpenAlex.
- Rewiring redox defense: Nrf2-driven antioxidant signaling as a gateway to programmed cell death activation in colorectal cancer.Genes & diseases · 2027Review
- Silibinin Triggers Mitochondrial Apoptosis and Declines Clonogenic Potential in Detroit 562 Human Pharyngeal Carcinoma Cells.Medicina (Kaunas, Lithuania) · 2025Article
- Clinical application prospects of traditional Chinese medicine as adjuvant therapy for metabolic reprogramming in colorectal cancer.Frontiers in immunology · 2025Review
- The Therapeutic Effects of Bioactive Compounds on Colorectal Cancer via PI3K/Akt/mTOR Signaling Pathway: A Critical Review.Food science & nutrition · 2024Review
- Targeting SMAD-Dependent Signaling: Considerations in Epithelial and Mesenchymal Solid Tumors.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Silibinin, a potential fasting mimetic, inhibits hepatocellular carcinoma by triggering extrinsic apoptosis.MedComm · 2024Article
- Natural Compounds Targeting the Autophagy Pathway in the Treatment of Colorectal Cancer.International journal of molecular sciences · 2023Review
- Deacetylation of ATG4B promotes autophagy initiation under starvation.Science advances · 2022Article
- Flavonoids Targeting the mTOR Signaling Cascades in Cancer: A Potential Crosstalk in Anti-Breast Cancer Therapy.Oxidative medicine and cellular longevity · 2022Review
- Silymarin (milk thistle extract) as a therapeutic agent in gastrointestinal cancer.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2021Review
- Targeting the hallmarks of cancer: the effects of silibinin on proliferation, cell death, angiogenesis, and migration in colorectal cancer.BMC complementary medicine and therapies · 2021Article
- Silibinin inhibits epithelial‑mesenchymal transition of renal cell carcinoma through autophagy‑dependent Wnt/β‑catenin signaling.International journal of molecular medicine · 2020Article
- Transcriptome profiling reveals Silibinin dose-dependent response network in non-small lung cancer cells.PeerJ · 2020Article
- Inhibition of phosphoenolpyruvate carboxykinase blocks lactate utilization and impairs tumor growth in colorectal cancer.Cancer & metabolism · 2019Article
- TAK1 mediates excessive autophagy via p38 and ERK in cisplatin-induced acute kidney injury.Journal of cellular and molecular medicine · 2018Article
- Silibinin sensitizes TRAIL-mediated apoptosis by upregulating DR5 through ROS-induced endoplasmic reticulum stress-CaOncotarget · 2018Article
- Silibinin Inhibits NSCLC Metastasis by Targeting the EGFR/LOX Pathway.Frontiers in pharmacology · 2018Article
- Peiminine inhibits colorectal cancer cell proliferation by inducing apoptosis and autophagy and modulating key metabolic pathways.Oncotarget · 2017Article
- Autophagy Induced by Areca Nut Extract Contributes to Decreasing Cisplatin Toxicity in Oral Squamous Cell Carcinoma Cells: Roles of Reactive Oxygen Species/AMPK Signaling.International journal of molecular sciences · 2017Article
- Silibinin and colorectal cancer chemoprevention: a comprehensive review on mechanisms and efficacy.Journal of biomedical research · 2016Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Small molecules with the potential to initiate different types of programmed cell death could be useful 'adjunct therapy' where current anticancer modalities fail to generate significant activity due to a defective apoptotic machinery or resistance of cancer cells to the specific death mechanism induced by that treatment. The current study identified silibinin, for the first time, as one such natural agent, having dual efficacy against colorectal cancer (CRC) cells. First, silibinin rapidly induced oxidative stress in CRC SW480 cells due to reactive oxygen species (ROS) generation with a concomitant dissipation of mitchondrial potential (ΔΨm) and cytochrome c release leading to mild apoptosis as a biological effect. However, with increased exposure to silibinin, cytoplasmic vacuolization intensified within the cells followed by sequestration of the organelles, which inhibits the further release of cytochrome c. Interestingly, this decrease in apoptotic response correlated with increased autophagic events as evidenced by tracking the dynamics of LC3-II within the cells. Mechanistic studies revealed that silibinin strongly inhibited PIK3CA-AKT-MTOR but activated MAP2K1/2-MAPK1/3 pathways for its biological effects. Corroborating these effects, endoplasmic reticulum stress was generated and glucose uptake inhibition as well as energy restriction were induced by silibinin, thus, mimicking starvation-like conditions. Further, the cellular damage to tumor cells by silibinin was severe and irreparable due to sustained interference in essential cellular processes such as mitochondrial metabolism, phospholipid and protein synthesis, suggesting that silibinin harbors a deadly 'double-edged sword' against CRC cells thereby further advocating its clinical effectiveness against this malignancy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.