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Transfer of healthy fibroblast-derived mitochondria to HeLa ρ0 and SAS ρ0 cells recovers the proliferation capabilities of these cancer cells under conventional culture medium, but increase their sensitivity to cisplatin-induced apoptotic death

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Abstract

Mitochondrial dysfunction is known to contribute to cancer initiation, progression, and chemo-and radio-resistance. However, the precise role of mitochondria in cancer is controversial. Hence, here we tried to further clarify the role of mitochondria in cancer by transferring healthy mitochondria to cancer cells, and also to cells with depleted mitochondrial DNA (ρ0). Healthy mitochondria were isolated from WI-38 cells and were transferred to HeLa, SAS, HeLa ρ0, and SAS ρ0 cells. Then, cell proliferation was verified. In addition, the cells were treated by different concentrations of cisplatin and assessed for apoptosis induction and quantifying the mRNA expression of apoptosis-related genes. Results revealed that incubation of the HeLa, SAS and HeLa ρ0 cells with 5 µg/ml of the isolated mitochondria for 24 h significantly (p < 0.001) increased cell proliferation compared to non-treated controls. Interestingly, the mitochondria transfer rescued the ρ0 cells and made them capable of growing under conventional culture medium. However, the number of apoptotic cells was significantly higher in the HeLa ρ0 cells that received the mitochondria (HeLa-Fibro-Mit) compared to the HeLa ρ0. Furthermore, the expression level of BCL-2 anti-apoptotic gene was down-regulated in both HeLa-Fibro-Mit and SAS-Fibro-Mit cell lines while the expression levels of the BAX, caspase8, caspase9, and AIF pro-apoptotic genes were upregulated. Our findings indicated that although the response of cancer cells to the mitochondria transfer is cancer-type dependent, but the introduction of normal exogenous mitochondria to some cancer cells might be considered as a potential novel therapeutic strategy.

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Acknowledgements

Part of this study was supported by Guilan University of Medical Sciences (Grant No: IR.GUMS.REC.1397.35) and JSPS KAKENHI (Grant-in Aid for Scientific Research C: No. 19K10318 to K.T).

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Author notes

  1. Amaneh Mohammadi Roushandeh and  Kazuo Tomita have equally contributed to this work.

Authors and Affiliations

  1. Medical Biotechnology Department, Paramedicine faculty, Guilan University of Medical Sciences, Rasht, Iran

    Amaneh Mohammadi Roushandeh & Mehryar Habibi Roudkenar

  2. Department of Applied Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan

    Amaneh Mohammadi Roushandeh, Kazuo Tomita, Kento Igarashi, Mehryar Habibi Roudkenar & Tomoaki Sato

  3. Division of Radiation Biology and Medicine, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai, Japan

    Yoshikazu Kuwahara

  4. Department of Pharmaceutical Biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

    Ali Jahanian-Najafabadi

  5. Cardiovascular Diseases Research Center, Department of Cardiology, Heshmat Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran

    Mehryar Habibi Roudkenar

Authors
  1. Amaneh Mohammadi Roushandeh
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Correspondence to Mehryar Habibi Roudkenar.

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Roushandeh, A.M., Tomita, K., Kuwahara, Y. et al. Transfer of healthy fibroblast-derived mitochondria to HeLa ρ0 and SAS ρ0 cells recovers the proliferation capabilities of these cancer cells under conventional culture medium, but increase their sensitivity to cisplatin-induced apoptotic death. Mol Biol Rep 47, 4401–4411 (2020). https://doi.org/10.1007/s11033-020-05493-5

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  • DOI: https://doi.org/10.1007/s11033-020-05493-5

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