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Apoptotic Effect of Saccharomyces cerevisiae on Human Colon Cancer SW480 Cells by Regulation of Akt/NF-ĸB Signaling Pathway

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Abstract

Drug resistance is one of the major problems, which causes recurrence of cancers. Therefore, complementary treatments are needed to improve the impacts of chemotherapy agents. The effect of probiotics as cancer-preventing agents through involvement in the activation of apoptotic pathways has been established. The present study sought to investigate how the heat-killed form of Saccharomyces cerevisiae (as a probiotic) could affect the Akt/NF-kB-induced apoptosis in colon cancer cells, the SW480 cell line. The cytotoxic effects of heat-killed yeast (HKY) and 5-fluorouracil (5-FU, as a positive control drug) were assayed using the MTT method. Morphological changes followed by apoptosis were examined using DAPI staining. The transcription and translation level of apoptosis genes were explored with qRT-PCR and western blotting. The data were analyzed using GraphPad Prism V6.0 Software. The results showed that HKY could induce apoptosis in colon cancer cell line through downregulation of p-Akt1, Rel A, Bcl-XL, pro-caspase 3, and pro-caspase 9 expressions, and upregulation of BAX, cleaved caspase-3, and cleaved caspase-9. Besides, Akt protein expression was not affected. It is noticeable that HKY had a better modulating effect on BAX expression compared with 5-FU. It was able to modulate Akt/NF-kB signaling pathway followed by the apoptotic cascade.

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Funding

This study was financially supported by grant No: 977521 of the National Institute for Medical Research Development (NIMAD), Tehran, Iran.

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Authors and Affiliations

  1. Nutrition Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Sara Shamekhi, Alireza Ostadrahimi & Nosratollah Zarghami

  2. Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

    Sara Shamekhi, Seyyed Abolghasem Mohammadi, Abolfazl Barzegari, Hajie Lotfi & Nosratollah Zarghami

  3. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Sara Shamekhi, Jalal Abdolalizadeh & Hajie Lotfi

  4. Faculty of Pharmacy, Department of Pharmaceutical Biotechnology, Tabriz University of Medical Sciences, Tabriz, Iran

    Jalal Abdolalizadeh

  5. Department of Plant Breeding and Biotechnology, Faculty of Agriculture, University of Tabriz, Tabriz, Iran

    Seyyed Abolghasem Mohammadi

  6. Department of Medical Microbiology, Faculty of Medicine, Istanbul Aydin University, Istanbul, Turkey

    Esat Bonabi

  7. Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

    Nosratollah Zarghami

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  1. Sara Shamekhi
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Correspondence to Nosratollah Zarghami.

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Shamekhi, S., Abdolalizadeh, J., Ostadrahimi, A. et al. Apoptotic Effect of Saccharomyces cerevisiae on Human Colon Cancer SW480 Cells by Regulation of Akt/NF-ĸB Signaling Pathway. Probiotics & Antimicro. Prot. 12, 311–319 (2020). https://doi.org/10.1007/s12602-019-09528-7

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