Lactobacilli Modulate Hypoxia-Inducible Factor (HIF)-1 Regulatory Pathway in Triple Negative Breast Cancer Cell Line
Objective Hypoxia-Inducible Factor (HIF)-1 plays an essential role in the body’s response to low oxygen concentrations and regulates expression of several genes implicated in homeostasis, vascularization, anaerobic metabolism as well as immunological responses. Increased levels of HIF-1α are asso...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Royan Institute (ACECR), Tehran
2016-07-01
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| Series: | Cell Journal |
| Subjects: | |
| Online Access: | http://celljournal.org/web/journal/article/3690/download |
| _version_ | 1818850664837545984 |
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| author | Ali Esfandiary Zahra Taherian-Esfahani Atieh Abedin-Do, Reza Mirfakhraie Mahdieh Shirzad Soudeh Ghafouri-Fard Elahe Motevaseli |
| author_facet | Ali Esfandiary Zahra Taherian-Esfahani Atieh Abedin-Do, Reza Mirfakhraie Mahdieh Shirzad Soudeh Ghafouri-Fard Elahe Motevaseli |
| author_sort | Ali Esfandiary |
| collection | DOAJ |
| description | Objective
Hypoxia-Inducible Factor (HIF)-1 plays an essential role in the body’s response to low oxygen concentrations and regulates expression of several genes implicated in homeostasis, vascularization, anaerobic metabolism as well as immunological responses. Increased levels of HIF-1α are associated with increased proliferation and more aggressive breast tumor development. Lactobacilli have been shown to exert anti-cancer effects on several malignancies including breast cancer. However, the exact mechanism of such effect is not clear yet. The aim of this study was to analyze the expression of selected genes from HIF pathway in a triple negative breast cancer cell line (expressing no estrogen and progesterone receptors as well as HER-2/Neu), MDA-MB-231, following treatment with two lactobacilli culture supernatants.
Materials and Methods
In this experimental study, we analyzed the expression of HIF-1α, SLC2A1, VHL, HSP90, XBP1 and SHARP1 genes from HIF pathway in MDA-MB-231 cells, before and after treatment with Lactobacillus crispatus and Lactobacillus rhamnosus culture supernatants (LCS and LRS, respectively) by means of quantitative reverse-transcription polymerase chain reaction (qRT-PCR).
Results
Both LRS and LCS had cytotoxic effects on MDA-MB-231 cells, while the former type was more cytotoxic. LRS dramatically down-regulated expression levels of the HIF-1α, HSP90 and SLC2A1 in the MDA-MB-231 cells. LCS had similar effect on the expression of HSP90, to what was observed in the LRS treatment. The expression level of tumor suppressor genes VHL and SHARP1 were also decreased in LCS treated cells.
Conclusion
Although both LCS and LRS had cytotoxic effects on the MDA-MB-231 cells, it is proposed that LRS could be more appropriate for pathway directed treatment modalities, as it did not decrease expression of tumor suppressor genes involved in HIF pathway. Down-regulation of HIF pathway mediated oncogenes by LRS suggests that the cytotoxic effects of this Lactobacillus may at least be partly caused by this mechanism. As previous studies have shown that inhibition of HIF-1α and HSP90 expressions have therapeutic impact on cancer treatment, the inhibitory effect of LRS on expression of these genes implies that this Lactobacillus can be used in treatment strategies. |
| first_indexed | 2024-12-19T06:52:44Z |
| format | Article |
| id | doaj.art-df23e5a1667c4989a590c53248a98df8 |
| institution | Directory Open Access Journal |
| issn | 2228-5806 2228-5814 |
| language | English |
| last_indexed | 2024-12-19T06:52:44Z |
| publishDate | 2016-07-01 |
| publisher | Royan Institute (ACECR), Tehran |
| record_format | Article |
| series | Cell Journal |
| spelling | doaj.art-df23e5a1667c4989a590c53248a98df82022-12-21T20:31:39ZengRoyan Institute (ACECR), TehranCell Journal2228-58062228-58142016-07-01182237244Lactobacilli Modulate Hypoxia-Inducible Factor (HIF)-1 Regulatory Pathway in Triple Negative Breast Cancer Cell LineAli Esfandiary0Zahra Taherian-Esfahani1Atieh Abedin-Do, Reza Mirfakhraie2 Mahdieh Shirzad3 Soudeh Ghafouri-Fard4Elahe Motevaseli5Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, IranDepartment of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, IranDepartment of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, IranDepartment of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, IranDepartment of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, IranDepartment of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, IranObjective Hypoxia-Inducible Factor (HIF)-1 plays an essential role in the body’s response to low oxygen concentrations and regulates expression of several genes implicated in homeostasis, vascularization, anaerobic metabolism as well as immunological responses. Increased levels of HIF-1α are associated with increased proliferation and more aggressive breast tumor development. Lactobacilli have been shown to exert anti-cancer effects on several malignancies including breast cancer. However, the exact mechanism of such effect is not clear yet. The aim of this study was to analyze the expression of selected genes from HIF pathway in a triple negative breast cancer cell line (expressing no estrogen and progesterone receptors as well as HER-2/Neu), MDA-MB-231, following treatment with two lactobacilli culture supernatants. Materials and Methods In this experimental study, we analyzed the expression of HIF-1α, SLC2A1, VHL, HSP90, XBP1 and SHARP1 genes from HIF pathway in MDA-MB-231 cells, before and after treatment with Lactobacillus crispatus and Lactobacillus rhamnosus culture supernatants (LCS and LRS, respectively) by means of quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Results Both LRS and LCS had cytotoxic effects on MDA-MB-231 cells, while the former type was more cytotoxic. LRS dramatically down-regulated expression levels of the HIF-1α, HSP90 and SLC2A1 in the MDA-MB-231 cells. LCS had similar effect on the expression of HSP90, to what was observed in the LRS treatment. The expression level of tumor suppressor genes VHL and SHARP1 were also decreased in LCS treated cells. Conclusion Although both LCS and LRS had cytotoxic effects on the MDA-MB-231 cells, it is proposed that LRS could be more appropriate for pathway directed treatment modalities, as it did not decrease expression of tumor suppressor genes involved in HIF pathway. Down-regulation of HIF pathway mediated oncogenes by LRS suggests that the cytotoxic effects of this Lactobacillus may at least be partly caused by this mechanism. As previous studies have shown that inhibition of HIF-1α and HSP90 expressions have therapeutic impact on cancer treatment, the inhibitory effect of LRS on expression of these genes implies that this Lactobacillus can be used in treatment strategies.http://celljournal.org/web/journal/article/3690/downloadBreast CancerLactobacillusHIF |
| spellingShingle | Ali Esfandiary Zahra Taherian-Esfahani Atieh Abedin-Do, Reza Mirfakhraie Mahdieh Shirzad Soudeh Ghafouri-Fard Elahe Motevaseli Lactobacilli Modulate Hypoxia-Inducible Factor (HIF)-1 Regulatory Pathway in Triple Negative Breast Cancer Cell Line Cell Journal Breast Cancer Lactobacillus HIF |
| title | Lactobacilli Modulate Hypoxia-Inducible Factor (HIF)-1 Regulatory Pathway in Triple Negative Breast Cancer Cell Line |
| title_full | Lactobacilli Modulate Hypoxia-Inducible Factor (HIF)-1 Regulatory Pathway in Triple Negative Breast Cancer Cell Line |
| title_fullStr | Lactobacilli Modulate Hypoxia-Inducible Factor (HIF)-1 Regulatory Pathway in Triple Negative Breast Cancer Cell Line |
| title_full_unstemmed | Lactobacilli Modulate Hypoxia-Inducible Factor (HIF)-1 Regulatory Pathway in Triple Negative Breast Cancer Cell Line |
| title_short | Lactobacilli Modulate Hypoxia-Inducible Factor (HIF)-1 Regulatory Pathway in Triple Negative Breast Cancer Cell Line |
| title_sort | lactobacilli modulate hypoxia inducible factor hif 1 regulatory pathway in triple negative breast cancer cell line |
| topic | Breast Cancer Lactobacillus HIF |
| url | http://celljournal.org/web/journal/article/3690/download |
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