ArticleInternational journal of oncology2013
Macrolide antibiotics block autophagy flux and sensitize to bortezomib via endoplasmic reticulum stress-mediated CHOP induction in myeloma cells.
Article in International journal of oncology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.
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Who cites it
61 citing papers in PubMed, 1 synthesis or guideline pooled it, 99 citations in OpenAlex.
- Combination therapy in combating cancer.Oncotarget · 2017Pooled it
- Oral cysteamine as an adjunct treatment in cystic fibrosis pulmonary exacerbations: An exploratory randomized clinical trial.PloS one · 2020Trial
- Off-target anti-leukemic effects of antibiotics: mechanisms and therapeutic insights.Cancer chemotherapy and pharmacology · 2026Review
- Two Worlds, One Battle: How Bacteria and Malignancies Converge on Drug Resistance.International journal of molecular sciences · 2026Review
- Endoplasmic reticulum stress in disease pathogenesis: its implications for therapy.Signal transduction and targeted therapy · 2026Review
- Targeting the proteasome in cancer therapy: development and future opportunities in natural products.Frontiers in pharmacology · 2026Review
- 3D collagen high-throughput screen identifies drugs that induce epithelial polarity and enhance chemotherapy response in colorectal cancer.Communications biology · 2025Article
- The Effect of Antibiotics on the Nervous System: Importance for Anesthesiology and Intensive Care.Antibiotics (Basel, Switzerland) · 2025Review
- Autophagy inhibition induced by EM-2 augments apoptosis via ROS-mediated ATM-Chk2-p53-p21 and MAPK pathway in lung and breast carcinoma.Frontiers in pharmacology · 2025Article
- Blockage of Autophagy for Cancer Therapy: A Comprehensive Review.International journal of molecular sciences · 2024Review
- Article
- Azithromycin, a potent autophagy inhibitor for cancer therapy, perturbs cytoskeletal protein dynamics.British journal of cancer · 2023Article
- Macrolide antibiotics activate the integrated stress response and promote tumor proliferation.Cell stress · 2023Article
- Autophagy: A Potential Therapeutic Target to Tackle Drug Resistance in Multiple Myeloma.International journal of molecular sciences · 2023Review
- Immunomodulatory role of azithromycin: Potential applications to radiation-induced lung injury.Frontiers in oncology · 2023Review
- Article
- Global Effect of COVID-19 Pandemic on Cancer Patients and its Treatment: A Systematic Review.Clinical complementary medicine and pharmacology · 2022Review
- The role of goblet cells and mucus in intestinal homeostasis.Nature reviews. Gastroenterology & hepatology · 2022Review
- Vitamin D/vitamin D receptor, autophagy, and infection.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2022Article
- Delivering macrolide antibiotics to heal a broken heart - And other inflammatory conditions.Advanced drug delivery reviews · 2022Review
1 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The specific 26S proteasome inhibitor bortezomib (BZ) potently induces autophagy, endoplasmic reticulum (ER) stress and apoptosis in multiple myeloma (MM) cell lines (U266, IM-9 and RPMI8226). The macrolide antibiotics including concanamycin A, erythromycin (EM), clarithromycin (CAM) and azithromycin (AZM) all blocked autophagy flux, as assessed by intracellular accumulation of LC3B-II and p62. Combined treatment of BZ and CAM or AZM enhanced cytotoxicity in MM cell lines, although treatment with either CAM or AZM alone exhibited almost no cytotoxicity. This combination also substantially enhanced aggresome formation, intracellular ubiquitinated proteins and induced the proapoptotic transcription factor CHOP (CADD153). Expression levels of the proapoptotic genes transcriptionally regulated by CHOP (BIM, BAX, DR5 and TRB3) were all enhanced by combined treatment with BZ plus CAM, compared with treatment with each reagent alone. Like the MM cell lines, the CHOP+/+ murine embryonic fibroblast (MEF) cell line exhibited enhanced cytotoxicity and upregulation of CHOP and its transcriptional targets with a combination of BZ and one of the macrolides. In contrast, CHOP-/- MEF cells exhibited resistance against BZ and almost completely canceled enhanced cytotoxicity with a combination of BZ and a macrolide. These data suggest that ER stress-mediated CHOP induction is involved in pronounced cytotoxicity. Simultaneously targeting two major intracellular protein degradation systems such as the ubiquitin-proteasome system by BZ and the autophagy-lysosome system by a macrolide antibiotic enhances ER stress-mediated apoptosis in MM cells. This result suggests the therapeutic possibility of using a macrolide antibiotic with a proteasome inhibitor for MM therapy.
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