ArticlePloS one2012
6-Shogaol induces apoptosis in human hepatocellular carcinoma cells and exhibits anti-tumor activity in vivo through endoplasmic reticulum stress.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 92 citations in OpenAlex.
- Ginger for Healthy Ageing: A Systematic Review on Current Evidence of Its Antioxidant, Anti-Inflammatory, and Anticancer Properties.Oxidative medicine and cellular longevity · 2022Pooled it
- Exploring natural products as apoptosis modulators in cancers: insights into natural product-based therapeutic strategies.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- The therapeutic potential of naturally occurring 6-shogaol: an updated comprehensive review.Inflammopharmacology · 2025Review
- Ginger-Derived Exosome-Like Nanoparticles Loaded With Indocyanine Green Enhances Phototherapy Efficacy for Breast Cancer.International journal of nanomedicine · 2025Article
- Plant-Derived Anti-Cancer Therapeutics and Biopharmaceuticals.Bioengineering (Basel, Switzerland) · 2024Review
- Research progress of ginger in the treatment of gastrointestinal tumors.World journal of gastrointestinal oncology · 2023Review
- Anticancer perspective of 6-shogaol: anticancer properties, mechanism of action, synergism and delivery system.Chinese medicine · 2023Review
- 6-shogaol is a potential treatment for Head and Neck Squamous Cell Carcinoma.International journal of medical sciences · 2023Article
- 6-Shogaol induces apoptosis in acute lymphoblastic leukaemia cells by targeting p53 signalling pathway and generation of reactive oxygen species.Journal of cellular and molecular medicine · 2021Article
- Cytotoxic effect of 6-Shogaol in Imatinib sensitive and resistant K562 cells.Molecular biology reports · 2021Article
- GRP78 targeting: Hitting two birds with a stone.Life sciences · 2020Review
- Anti-Survival and Pro-Apoptotic Effects of 6-Shogaol on SW872 Human Liposarcoma Cells via Control of the Intrinsic Caspase Pathway, STAT-3, AMPK, and ER Stress.Biomolecules · 2020Article
- Gingers and Their Purified Components as Cancer Chemopreventative Agents.Molecules (Basel, Switzerland) · 2019Review
- Attenuation of autophagy flux by 6-shogaol sensitizes human liver cancer cells to TRAIL-induced apoptosis via p53 and ROS.International journal of molecular medicine · 2019Article
- The possibility of using shogaol for treatment of ulcerative colitis.Iranian journal of basic medical sciences · 2018Article
- Anti-Cancer Natural Products and Their Bioactive Compounds Inducing ER Stress-Mediated Apoptosis: A Review.Nutrients · 2018Review
- Next-Gen Therapeutics for Skin Cancer: Nutraceuticals.Nutrition and cancer · 2018Review
- Hepatocyte growth factor suppresses hypoxia/reoxygenation-induced XO activation in cardiac microvascular endothelial cells.Heart and vessels · 2015Article
- Yakammaoto inhibits enterovirus 71 infection by reducing viral attachment, internalization, replication, and translation.The Kaohsiung journal of medical sciences · 2015Article
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Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
6-Shogaol is an active compound isolated from Ginger (Zingiber officinale Rosc). In this work, we demonstrated that 6-shogaol induces apoptosis in human hepatocellular carcinoma cells in relation to caspase activation and endoplasmic reticulum (ER) stress signaling. Proteomic analysis revealed that ER stress was accompanied by 6-shogaol-induced apoptosis in hepatocellular carcinoma cells. 6-shogaol affected the ER stress signaling by regulating unfolded protein response (UPR) sensor PERK and its downstream target eIF2α. However, the effect on the other two UPR sensors IRE1 and ATF6 was not obvious. In prolonged ER stress, 6-shogaol inhibited the phosphorylation of eIF2α and triggered apoptosis in SMMC-7721 cells. Salubrinal, an activator of the PERK/eIF2α pathway, strikingly enhanced the phosphorylation of eIF2α in SMMC-7721 cells with no toxicity. However, combined treatment with 6-shogaol and salubrinal resulted in significantly increase of apoptosis and dephosphorylation of eIF2α. Overexpression of eIF2α prevented 6-shogaol-mediated apoptosis in SMMC-7721 cells, whereas inhibition of eIF2α by small interfering RNA markedly enhanced 6-shogaol-mediated cell death. Furthermore, 6-shogaol-mediated inhibition of tumor growth of mouse SMMC-7721 xenograft was associated with induction of apoptosis, activation of caspase-3, and inactivation of eIF2α. Altogether our results indicate that the PERK/eIF2α pathway plays an important role in 6-shogaol-mediated ER stress and apoptosis in SMMC-7721 cells in vitro and in vivo.
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