Dataset Information

A preclinical evaluation of antimycin a as a potential antilung cancer stem cell agent.

ABSTRACT: Drug resistance and tumor recurrence are major obstacles in treating lung cancer patients. Accumulating evidence considers lung cancer stem cells (CSCs) as the major contributor to these clinical challenges. Agents that can target lung CSCs could potentially provide a more effective treatment than traditional chemotherapy. Here, we utilized the side-population (SP) method to isolate lung CSCs from A549 and PC-9 cell lines. Subsequently, a high throughput platform, connectivity maps (CMAPs), was used to identify potential anti-CSC agents. An antibiotic, antimycin A (AMA), was identified as a top candidate. SP A549 cells exhibited an elevated stemness profile, including Nanog, ? -catenin, Sox2, and CD133, and increased self-renewal ability. AMA treatment was found to suppress ? -catenin signaling components and tumor sphere formation. Furthermore, AMA treatment decreased the proliferation of gefitinib-resistant PC-9/GR cells and percentage of SP population. AMA demonstrated synergistic suppression of PC-9/GR cell viability when combined with gefitinib. Finally, AMA treatment suppressed tumorigenesis in mice inoculated with A549 SP cells. Collectively, we have identified AMA using CMAP as a novel antilung CSC agent, which acts to downregulate ? -catenin signaling. The combination of AMA and targeted therapeutic agents could be considered for overcoming drug resistance and relapse in lung cancer patients.

SUBMITTER: Yeh CT

PROVIDER: S-EPMC3693105 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A preclinical evaluation of antimycin a as a potential antilung cancer stem cell agent.

Yeh Chi-Tai CT Su Chun-Li CL Huang Chi-Ying F CY Lin Justin Kung-Yi JK Lee Wei-Hwa WH Chang Peter M-H PM Kuo Yu-Lun YL Liu Yu-Wen YW Wang Liang-Shun LS Wu Chih-Hsiung CH Shieh Yi-Shing YS Jan Yi-Hua YH Chuang Yung-Jen YJ Hsiao Michael M Wu Alexander T H AT

Evidence-based complementary and alternative medicine : eCAM 20130611

Drug resistance and tumor recurrence are major obstacles in treating lung cancer patients. Accumulating evidence considers lung cancer stem cells (CSCs) as the major contributor to these clinical challenges. Agents that can target lung CSCs could potentially provide a more effective treatment than traditional chemotherapy. Here, we utilized the side-population (SP) method to isolate lung CSCs from A549 and PC-9 cell lines. Subsequently, a high throughput platform, connectivity maps (CMAPs), was ...[more]

PMID: 23840269

Similar Datasets

Project description:Cell therapy is a key technology to prevent sacrificing normal skin. Although some studies have shown the promise of human epidermal stem cells (EpiSCs), the efficacy, biosafety and quality control of EpiSC therapy have not been systematically reported. The biosafety, stemness maintenance and wound repair of EpiSC were systematically verified by in vitro and in vivo experiments. EpiSC were prepared from the foreskin using a collagen type IV rapid adherence method. The EpiSCs were identified by flow cytometry, immunofluorescence staining and cell morphology. The well-growing passage 1 (P1) EpiSCs were used to determine the proliferation curve (counting method). EpiSC clone formation assay was performed by Giemsa staining. Nude mice were used to prepare a full-thickness skin defect wound model to detect the repair effect of EpiSCs. The biosafety of EpiSCs was double tested in vitro and in vivo. The results showed that the expression of specific markers and clone formation efficiency was stable when passage 1 (P1) to P8 cells were cultured, and the stemness rate of P8 cells was close to 85.1%. EpiSCs were expanded in vitro for 25 days, the number of cells reached 2.5 × 108, and the transplantable area was approximately 75% of the total body surface area (TBSA). At 45 days, the total number of cells was approximately 30 billion, and the transplantable area was approximately the size of a volleyball court. A nude mouse wound model indicated that EpiSCs could rapidly close a wound. On postinjury day 7, the wound epithelialization rate in the cell transplantation group was significantly higher than that in the NaCl group (P < 0.05). In vitro, cell senescence increased, and telomerase activity decreased in P1 to P8 EpiSCs. In vivo, there were no solid tumors or metastatic tumors after EpiSC (P8) transplantation. In addition, the quality control of cultured cells met the clinical application criteria for cell therapy. This preclinical study showed the stability and biosafety of human EpiSC therapy for wound repair.

Dataset Information

A preclinical evaluation of antimycin a as a potential antilung cancer stem cell agent.

Publications

A preclinical evaluation of antimycin a as a potential antilung cancer stem cell agent.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets