Journal
IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL
Volume 58, Issue 8, Pages 679-692Publisher
SPRINGER
DOI: 10.1007/s11626-022-00714-6
Keywords
Tadpole blastema; Tissue regeneration; Embryonal rhabdomyosarcoma; Cytotoxicity; Programmed cell death
Categories
Funding
- South Africa Medical Research Council (SA MRC)
- South Africa National Research Foundation (SA NRF)
- Cancer Association of South Africa (CANSA)
- University of Cape Town
- NRF
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This study shows that tadpole tail blastema extracts (TAD) from the stream frog have anti-cancer potential against embryonal rhabdomyosarcoma (ERMS) cells. TAD inhibits cell viability, induces senescence and apoptosis, and activates DNA damage and stress signaling pathways. Furthermore, TAD inhibits tumor promoters and proteins required for cancer cell survival.
Amphibians have regenerative capacity and are resistant to developing cancer. This suggests that the developing blastema, located at the tissue regeneration site, may secrete anti-cancer factors. Here, we investigate the anti-cancer potential of tadpole tail blastema extracts (TAD) from the stream frog, Strongylopus grayii, in embryonal rhabdomyosarcoma (ERMS) cells. ERMS originates in skeletal muscle tissue and is a common pediatric soft tissue sarcoma. We show using MTT assays that TAD inhibited ERMS cell viability in a concentration-dependent manner, and phase contrast/fluorescent microscopy revealed that it induced morphological markers of senescence and apoptosis. Western blotting showed that this was associated with DNA damage (gamma H2AX) and activation of the p38/MAPK stress signaling pathway as well as molecular markers of senescence (p16(INK4a)), apoptosis (cleaved PARP), and inhibition of cell cycle promoters (cyclin A, CDK2, and cyclin B1). Furthermore, proteomics followed by gene ontology analyses showed that TAD treatment inhibited known tumor promoters and proteins required for cancer cell survival. Lastly, using the LINCS drug perturbation library, we show that there is an overlap between the proteomics signature induced by TAD and common anti-cancer drugs. Taken together, this study provides novel evidence that TAD exhibits cytotoxicity in ERMS cells.
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