A radiosensitizer, gallotannin-rich extract from Bouea macrophylla seeds, inhibits radiation-induced epithelial-mesenchymal transition in breast cancer cells

BMC Complementary Medicine and Therapies

Wipob Suttana¹  Padchanee Sangthong²  Sittiruk Roytrakul³  Aphidet Duangya⁴  Jiraporn Kantapan⁵  Siwaphon Paksee⁵  Nathupakorn Dechsupa⁵  Sucheewin Krobthong⁶ 

[1]Department of Biomedical Science, School of Health Science, Mae Fah Luang University, 57100, Chiang Rai, Thailand

[2]Department of Chemistry, Faculty of Science, Chiang Mai University, 50200, Chiang Mai, Thailand

[3]Research Center on Chemistry for Development of Health Promoting Products from Northern Resources, Chiang Mai University, 50200, Chiang Mai, Thailand

[4]Functional Ingredients and Food Innovation Research Group, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), 12120, Pathum Thani, Thailand

[5]Interdisciplinary Program of Biotechnology, Graduate School, Chiang Mai University, 50200, Chiang Mai, Thailand

[6]Molecular Imaging and Therapy Research Unit, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, 50200, Chiang Mai, Thailand

[7]National Omics Center (NOC), National Science and Technology Development Agency (NSTDA), 12120, Pathum Thani, Thailand

关键词: Radiosensitizer;    EMT;    Cancer stem cells;    Breast cancer;    Senescence;    Apoptosis;    Maprang seed extract;    Radiotherapy;    Proteomics;   

DOI  :  10.1186/s12906-021-03363-6

来源: Springer

【 摘 要 】

BackgroundRadioresistance can pose a significant obstacle to the effective treatment of breast cancers. Epithelial–mesenchymal transition (EMT) is a critical step in the acquisition of stem cell traits and radioresistance. Here, we investigated whether Maprang seed extract (MPSE), a gallotannin-rich extract of seed from Bouea macrophylla Griffith, could inhibit the radiation-induced EMT process and enhance the radiosensitivity of breast cancer cells.MethodsBreast cancer cells were pre-treated with MPSE before irradiation (IR), the radiosensitizing activity of MPSE was assessed using the colony formation assay. Radiation-induced EMT and stemness phenotype were identified using breast cancer stem cells (CSCs) marker (CD24−/low/CD44+) and mammosphere formation assay. Cell motility was determined via the wound healing assay and transwell migration. Radiation-induced cell death was assessed via the apoptosis assay and SA-β-galactosidase staining for cellular senescence. CSCs- and EMT-related genes were confirmed by real-time PCR (qPCR) and Western blotting.ResultsPre-treated with MPSE before irradiation could reduce the clonogenic activity and enhance radiosensitivity of breast cancer cell lines with sensitization enhancement ratios (SERs) of 2.33 and 1.35 for MCF7 and MDA-MB231cells, respectively. Pretreatment of breast cancer cells followed by IR resulted in an increased level of DNA damage maker (γ-H2A histone family member) and enhanced radiation-induced cell death. Irradiation induced EMT process, which displayed a significant EMT phenotype with a down-regulated epithelial marker E-cadherin and up-regulated mesenchymal marker vimentin in comparison with untreated breast cancer cells. Notably, we observed that pretreatment with MPSE attenuated the radiation-induced EMT process and decrease some stemness-like properties characterized by mammosphere formation and the CSC marker. Furthermore, pretreatment with MPSE attenuated the radiation-induced activation of the pro-survival pathway by decrease the expression of phosphorylation of ERK and AKT and sensitized breast cancer cells to radiation.ConclusionMPSE enhanced the radiosensitivity of breast cancer cells by enhancing IR-induced DNA damage and cell death, and attenuating the IR-induced EMT process and stemness phenotype via targeting survival pathways PI3K/AKT and MAPK in irradiated breast cancer cells. Our findings describe a novel strategy for increasing the efficacy of radiotherapy for breast cancer patients using a safer and low-cost natural product, MPSE.

【 授权许可】

CC BY