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Updated: Jun 6, 2026
A Three-dimensional Model of Spheroids to Study Colon Cancer Stem Cells
Published on: January 22, 2021
Secretome-based proteomics reveals sulindac-modulated proteins released from colon cancer cells
Hong Ji1, David W Greening, Eugene A Kapp
1Joint Proteomics Laboratory, Ludwig Institute for Cancer Research and the Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Abstract:
Although experiments in rodents and human population-based studies have demonstrated the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) such as sulindac in colorectal cancer (CRC) prevention, a detailed knowledge of the underlying mechanism of action of this drug is limited. To better understand the chemopreventitive effects of sulindac, especially early sulindac-induced apoptotic events, we used the CRC cell line LIM1215 as an experimental model, focusing on proteins secreted into the LIM1215 culture medium - i.e., the secretome. This subproteome comprises both soluble-secreted proteins and exosomes (30-100 nm diameter membrane vesicles released by several cell types). Selected secretome proteins whose expression levels were dysregulated by 1 mM sulindac treatment over 16 h were analyzed using 2-D DIGE, cytokine array, Western blotting, and MS. Overall, 150 secreted proteins were identified, many of which are implicated in molecular and cellular functions such as cell proliferation, differentiation, adhesion, invasion, angiogenesis, metastasis, and apoptosis. Our secretome-based proteomic studies have identified several secreted modulators of sulindac-induced apoptosis action (e.g., Mac-2 binding protein, Alix, 14-3-3 isoforms, profilin-1, calumenin/Cab45 precursors, and the angiogenic/tumor growth factors interleukin 8 (IL-8) and growth related oncogene (GRO-α)) that are likely to improve our understanding of the chemopreventitive action of this NSAID in CRC.
Insights
Nonsteroidal anti-inflammatory drugs (NSAIDs) like sulindac show promise for colorectal cancer (CRC) prevention. This study identified key secreted proteins involved in sulindac-induced apoptosis, advancing our understanding of its chemopreventive mechanisms.
Area of Science:
- Proteomics
- Cancer Biology
- Molecular Pharmacology
Background:
- Nonsteroidal anti-inflammatory drugs (NSAIDs) demonstrate efficacy in colorectal cancer (CRC) prevention.
- The precise mechanism of action for NSAIDs, particularly sulindac, in CRC chemoprevention remains incompletely understood.
- Early apoptotic events induced by sulindac are crucial for its chemopreventive effects.
Purpose of the Study:
- To elucidate the chemopreventive mechanism of sulindac in colorectal cancer (CRC).
- To investigate early sulindac-induced apoptotic events by analyzing the secretome of CRC cells.
- To identify specific secreted proteins modulated by sulindac treatment that influence apoptosis.
Main Methods:
- Utilized the LIM1215 colorectal cancer (CRC) cell line as an experimental model.
- Analyzed the secretome, including soluble proteins and exosomes, following sulindac treatment.
- Employed 2-D DIGE, cytokine array, Western blotting, and mass spectrometry (MS) for protein identification and analysis.
Main Results:
- Identified 150 secreted proteins dysregulated by sulindac treatment.
- These proteins are involved in critical cellular functions including proliferation, adhesion, angiogenesis, metastasis, and apoptosis.
- Key modulators of sulindac-induced apoptosis were identified, such as Mac-2 binding protein, Alix, 14-3-3 isoforms, profilin-1, calumenin/Cab45 precursors, IL-8, and GRO-α.
Conclusions:
- Secretome-based proteomic analysis provides novel insights into sulindac's chemopreventive action in CRC.
- Identified secreted proteins offer potential targets for understanding and enhancing sulindac's therapeutic effects.
- This research contributes to a deeper comprehension of how sulindac induces apoptosis and prevents colorectal cancer.
