Low-dose phthalates promote breast cancer stem cell properties via the oncogene ΔNp63α and the Sonic hedgehog pathway
Background: The omnipresence of human phthalate (PAE) exposure is linked to various adverse health issues, including breast cancer. However, the effects of low-dose PAE exposure on breast cancer stem cells (BCSCs) and the underlying mechanism remain unexplored. Methods: BCSCs from breast cancer cell...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-03-01
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| Series: | Ecotoxicology and Environmental Safety |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651323001094 |
| _version_ | 1797902955330928640 |
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| author | Wan-shuang Cao Meng-jiu Zhao Yue Chen Jian-yun Zhu Chun-feng Xie Xiao-ting Li Shan-shan Geng Cai-yun Zhong Jin-yan Fu Jie-shu Wu |
| author_facet | Wan-shuang Cao Meng-jiu Zhao Yue Chen Jian-yun Zhu Chun-feng Xie Xiao-ting Li Shan-shan Geng Cai-yun Zhong Jin-yan Fu Jie-shu Wu |
| author_sort | Wan-shuang Cao |
| collection | DOAJ |
| description | Background: The omnipresence of human phthalate (PAE) exposure is linked to various adverse health issues, including breast cancer. However, the effects of low-dose PAE exposure on breast cancer stem cells (BCSCs) and the underlying mechanism remain unexplored. Methods: BCSCs from breast cancer cell lines (MDA-MB-231 and MCF-7) were enriched using a tumorsphere formation assay. Gene and protein expression was detected by measurement of quantitative real-time reverse transcription PCR, western blot, and immunofluorescence assays. Transient transfection assays were used to evaluate the involvement of Gli1, a signaling pathway molecule and ΔNp63α, an oncogene in influencing the PAE-induced characteristics of BCSCs. Results: PAE (butylbenzyl phthalate, BBP; di-butyl phthalate, DBP; di-2-ethylhexyl phthalate, DEHP) exposure of 10−9 M significantly promoted the tumorsphere formation ability in BCSCs. Breast cancer spheroids with a 10−9 M PAE exposure had higher levels of BCSC marker mRNA and protein expression, activated sonic hedgehog (SHH) pathway, and increased mRNA and protein levels of an oncogene, ΔNp63α. Furthermore, suppression of the SHH pathway attenuated the effects of PAEs on BCSCs. And the overexpression of ΔNp63α enhanced PAE-induced characteristics of BCSCs, while low expression of ΔNp63α inhibited the promotion effects of PAEs on BCSCs and the SHH pathway. Conclusion: Low-dose PAE exposure promoted the stem cell properties of BCSCs in a ΔNp63α- and SHH-dependent manner. The influence of low-dose exposure of PAEs and its relevance for the lowest observed effect concentrations requires further investigation, and the precise underlying mechanism needs to be further explored. |
| first_indexed | 2024-04-10T09:25:22Z |
| format | Article |
| id | doaj.art-5908883045034626aa1bab50db25636e |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-04-10T09:25:22Z |
| publishDate | 2023-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-5908883045034626aa1bab50db25636e2023-02-20T04:08:40ZengElsevierEcotoxicology and Environmental Safety0147-65132023-03-01252114605Low-dose phthalates promote breast cancer stem cell properties via the oncogene ΔNp63α and the Sonic hedgehog pathwayWan-shuang Cao0Meng-jiu Zhao1Yue Chen2Jian-yun Zhu3Chun-feng Xie4Xiao-ting Li5Shan-shan Geng6Cai-yun Zhong7Jin-yan Fu8Jie-shu Wu9Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing 211166, ChinaDepartment of Maternal, Child and Adolescent Health, School of Public Health, Nanjing Medical University, Nanjing 211166, ChinaDepartment of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing 211166, ChinaDepartment of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing 211166, ChinaDepartment of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing 211166, ChinaDepartment of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing 211166, ChinaDepartment of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing 211166, ChinaDepartment of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Cancer Research Division, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, ChinaDepartment of Nutrition, Wuxi Maternal and Child Health Care Hospital, Wuxi 214002, China; Corresponding authors.Department of Maternal, Child and Adolescent Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Corresponding authors.Background: The omnipresence of human phthalate (PAE) exposure is linked to various adverse health issues, including breast cancer. However, the effects of low-dose PAE exposure on breast cancer stem cells (BCSCs) and the underlying mechanism remain unexplored. Methods: BCSCs from breast cancer cell lines (MDA-MB-231 and MCF-7) were enriched using a tumorsphere formation assay. Gene and protein expression was detected by measurement of quantitative real-time reverse transcription PCR, western blot, and immunofluorescence assays. Transient transfection assays were used to evaluate the involvement of Gli1, a signaling pathway molecule and ΔNp63α, an oncogene in influencing the PAE-induced characteristics of BCSCs. Results: PAE (butylbenzyl phthalate, BBP; di-butyl phthalate, DBP; di-2-ethylhexyl phthalate, DEHP) exposure of 10−9 M significantly promoted the tumorsphere formation ability in BCSCs. Breast cancer spheroids with a 10−9 M PAE exposure had higher levels of BCSC marker mRNA and protein expression, activated sonic hedgehog (SHH) pathway, and increased mRNA and protein levels of an oncogene, ΔNp63α. Furthermore, suppression of the SHH pathway attenuated the effects of PAEs on BCSCs. And the overexpression of ΔNp63α enhanced PAE-induced characteristics of BCSCs, while low expression of ΔNp63α inhibited the promotion effects of PAEs on BCSCs and the SHH pathway. Conclusion: Low-dose PAE exposure promoted the stem cell properties of BCSCs in a ΔNp63α- and SHH-dependent manner. The influence of low-dose exposure of PAEs and its relevance for the lowest observed effect concentrations requires further investigation, and the precise underlying mechanism needs to be further explored.http://www.sciencedirect.com/science/article/pii/S0147651323001094Breast cancer stem cellsPhthalatesSonic hedgehog pathwayΔNp63αLow dose |
| spellingShingle | Wan-shuang Cao Meng-jiu Zhao Yue Chen Jian-yun Zhu Chun-feng Xie Xiao-ting Li Shan-shan Geng Cai-yun Zhong Jin-yan Fu Jie-shu Wu Low-dose phthalates promote breast cancer stem cell properties via the oncogene ΔNp63α and the Sonic hedgehog pathway Ecotoxicology and Environmental Safety Breast cancer stem cells Phthalates Sonic hedgehog pathway ΔNp63α Low dose |
| title | Low-dose phthalates promote breast cancer stem cell properties via the oncogene ΔNp63α and the Sonic hedgehog pathway |
| title_full | Low-dose phthalates promote breast cancer stem cell properties via the oncogene ΔNp63α and the Sonic hedgehog pathway |
| title_fullStr | Low-dose phthalates promote breast cancer stem cell properties via the oncogene ΔNp63α and the Sonic hedgehog pathway |
| title_full_unstemmed | Low-dose phthalates promote breast cancer stem cell properties via the oncogene ΔNp63α and the Sonic hedgehog pathway |
| title_short | Low-dose phthalates promote breast cancer stem cell properties via the oncogene ΔNp63α and the Sonic hedgehog pathway |
| title_sort | low dose phthalates promote breast cancer stem cell properties via the oncogene δnp63α and the sonic hedgehog pathway |
| topic | Breast cancer stem cells Phthalates Sonic hedgehog pathway ΔNp63α Low dose |
| url | http://www.sciencedirect.com/science/article/pii/S0147651323001094 |
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