Open Access

Differential regulation of mitochondrial complex I and oxidative stress based on metastatic potential of colorectal cancer cells

  • Authors:
    • Neeraj Kumar Rai
    • Shashank Mathur
    • Suraj Kumar Singh
    • Meenakshi Tiwari
    • Vijay Kumar Singh
    • Rizwanul Haque
    • Swasti Tiwari
    • Lokendra Kumar Sharma
  • View Affiliations

  • Published online on: September 30, 2020     https://doi.org/10.3892/ol.2020.12176
  • Article Number: 313
  • Copyright: © Rai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Mitochondria serve a vital role in cellular homeostasis as they regulate cell proliferation and death pathways, which are attributed to mitochondrial bioenergetics, free radicals and metabolism. Alterations in mitochondrial functions have been reported in various diseases, including cancer. Colorectal cancer (CRC) is one of the most common metastatic cancer types with high mortality rates. Although mitochondrial oxidative stress has been associated with CRC, its specific mechanism and contribution to metastatic progression remain poorly understood. Therefore, the aims of the present study were to investigate the role of mitochondria in CRC cells with low and high metastatic potential and to evaluate the contribution of mitochondrial respiratory chain (RC) complexes in oncogenic signaling pathways. The present results demonstrated that cell lines with low metastatic potential were resistant to mitochondrial complex I (C‑I)‑mediated oxidative stress, and had C‑I inhibition with impaired mitochondrial functions. These adaptations enabled cells to cope with higher oxidative stress. Conversely, cells with high metastatic potential demonstrated functional C‑I with improved mitochondrial function due to coordinated upregulation of mitochondrial biogenesis and metabolic reprogramming. Pharmacological inhibition of C‑I in high metastatic cells resulted in increased sensitivity to cell death and decreased metastatic signaling. The present findings identified the differential regulation of mitochondrial functions in CRC cells, based on CRC metastatic potential. Specifically, it was suggested that a functional C‑I is required for high metastatic features of cancer cells, and the role of C‑I could be further examined as a potential target in the development of novel therapies for diagnosing high metastatic cancer types.
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December-2020
Volume 20 Issue 6

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Rai NK, Mathur S, Singh SK, Tiwari M, Singh VK, Haque R, Tiwari S and Sharma LK: Differential regulation of mitochondrial complex I and oxidative stress based on metastatic potential of colorectal cancer cells. Oncol Lett 20: 313, 2020
APA
Rai, N.K., Mathur, S., Singh, S.K., Tiwari, M., Singh, V.K., Haque, R. ... Sharma, L.K. (2020). Differential regulation of mitochondrial complex I and oxidative stress based on metastatic potential of colorectal cancer cells. Oncology Letters, 20, 313. https://doi.org/10.3892/ol.2020.12176
MLA
Rai, N. K., Mathur, S., Singh, S. K., Tiwari, M., Singh, V. K., Haque, R., Tiwari, S., Sharma, L. K."Differential regulation of mitochondrial complex I and oxidative stress based on metastatic potential of colorectal cancer cells". Oncology Letters 20.6 (2020): 313.
Chicago
Rai, N. K., Mathur, S., Singh, S. K., Tiwari, M., Singh, V. K., Haque, R., Tiwari, S., Sharma, L. K."Differential regulation of mitochondrial complex I and oxidative stress based on metastatic potential of colorectal cancer cells". Oncology Letters 20, no. 6 (2020): 313. https://doi.org/10.3892/ol.2020.12176