ArticlePloS one2017
HSPA6 augments garlic extract-induced inhibition of proliferation, migration, and invasion of bladder cancer EJ cells; Implication for cell cycle dysregulation, signaling pathway alteration, and transcription factor-associated MMP-9 regulation.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 67 citations in OpenAlex.
- Targeting ferroptosis with culinary spices: a dietary strategy for neuroprotection via the Nrf2/GPX4 axis.Frontiers in nutrition · 2026Review
- PERP suppresses breast cancer metastasis via the ATF3-HSPA6 signaling pathway.The Journal of international medical research · 2025Article
- Cracking the Sulfur Code: Garlic Bioactive Molecules as Multi-Target Blueprints for Drug Discovery.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Carbonic Anhydrase IX Induces Human Osteosarcoma Cell Metastasis by Activating HSPA6 Expression Through the AMPK Signalling Pathway.Journal of cellular and molecular medicine · 2025Article
- The edible ethanol extract ofNutrition research and practice · 2025Article
- Machine Learning Analysis of RNA-Seq Data Identifies Key Gene Signatures and Pathways in Mpox Virus-Induced Gastrointestinal Complications Using Colon Organoid Models.International journal of molecular sciences · 2024Article
- Elotuzumab Enhances CD16-Independent NK Cell-Mediated Cytotoxicity against Myeloma Cells by Upregulating Several NK Cell-Enhancing Genes.Journal of immunology research · 2024Article
- Garlic bioactive substances and their therapeutic applications for improving human health: a comprehensive review.Frontiers in immunology · 2024Review
- Therapeutic effects of garlic (Heliyon · 2023Article
- Comparison of Antioxidant and Antiproliferative Effects of Various Forms of Garlic and Ramsons.Molecules (Basel, Switzerland) · 2023Article
- Potential use of garlic products in ruminant feeding: A review.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2023Review
- Bioavailability of Organosulfur Compounds after the Ingestion of Black Garlic by Healthy Humans.Antioxidants (Basel, Switzerland) · 2023Article
- Natural Products as New Approaches for Treating Bladder Cancer: From Traditional Medicine to Novel Drug Discovery.Pharmaceutics · 2023Review
- BARX1 promotes osteosarcoma cell proliferation and invasion by regulating HSPA6 expression.Journal of orthopaedic surgery and research · 2023Article
- HSPA6, a novel prognostic and therapeutic biomarker, associated with Ming classification in gastric cancer.Journal of clinical laboratory analysis · 2023Article
- Medicinal and therapeutic properties of garlic, garlic essential oil, and garlic-based snack food: An updated review.Frontiers in nutrition · 2023Review
- HSPA6 and its role in cancers and other diseases.Molecular biology reports · 2022Review
- RNA-Seq transcriptome analysis reveals Maackia amurensis leukoagglutinin has antitumor activity in human anaplastic thyroid cancer cells.Molecular biology reports · 2022Article
- High abundance of CDC45 inhibits cell proliferation through elevation of HSPA6.Cell proliferation · 2022Article
- An immune-related prognostic signature for thyroid carcinoma to predict survival and response to immune checkpoint inhibitors.Cancer immunology, immunotherapy : CII · 2022Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although recent studies have demonstrated the anti-tumor effects of garlic extract (GE), the exact molecular mechanism is still unclear. In this study, we investigated the molecular mechanism associated with the inhibitory action of GE against bladder cancer EJ cell responses. Treatment with GE significantly inhibited proliferation of EJ cells dose-dependently through G2/M-phase cell cycle arrest. This G2/M-phase cell cycle arrest by GE was due to the activation of ATM and CHK2, which appears to inhibit phosphorylation of Cdc25C (Ser216) and Cdc2 (Thr14/Tyr15), this in turn was accompanied by down-regulation of cyclin B1 and up-regulation of p21WAF1. Furthermore, GE treatment was also found to induce phosphorylation of MAPK (ERK1/2, p38MAPK, and JNK) and AKT. In addition, GE impeded the migration and invasion of EJ cells via inhibition of MMP-9 expression followed by decreased binding activities of AP-1, Sp-1, and NF-κB motifs. Based on microarray datasets, we selected Heat shock protein A6 (HSPA6) as the most up-regulated gene responsible for the inhibitory effects of GE. Interestingly, overexpression of HSPA6 gene resulted in an augmentation effect with GE inhibiting proliferation, migration, and invasion of EJ cells. The augmentation effect of HSPA6 was verified by enhancing the induction of G2/M-phase-mediated ATM-CHK2-Cdc25C-p21WAF1-Cdc2 cascade, phosphorylation of MAPK and AKT signaling, and suppression of transcription factor-associated MMP-9 regulation in response to GE in EJ cells. Overall, our novel results indicate that HSPA6 reinforces the GE-mediated inhibitory effects of proliferation, migration, and invasion of EJ cells and may provide a new approach for therapeutic treatment of malignancies.
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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.