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Penicillin disrupts mitochondrial function and induces autophagy in colorectal cancer cell lines

  • Authors:
    • Fei Hu
    • Yu Wu
    • Cheng Liu
    • Yingchao Zhu
    • Shazhou Ye
    • Yang Xi
    • Wei Cui
    • Shizhong Bu
  • View Affiliations / Copyright

    Affiliations: Diabetes Research Center, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, P.R. China, Department of Colorectal Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang 315211, P.R. China
    Copyright: © Hu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 691
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    Published online on: August 1, 2021
       https://doi.org/10.3892/ol.2021.12952
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Abstract

Colorectal cancer is a common malignant tumor of the gastrointestinal tract. Currently, the main treatment is surgical resection, which can be combined with other treatments. However, treatment efficacy is poor, and colorectal cancer is prone to relapse and metastasis; thus, identifying an effective anti‑cancer drug is an urgent requirement. The present study examined the antagonistic effect of penicillin on cultured colorectal cancer cells and the related mechanism. A MTT assay was used to assess the growth of the colorectal cancer cells treated with penicillin and to determine the optimal drug concentration. The wound healing and Transwell invasion assays were performed to investigate the effect of penicillin on the migration and invasion of the colorectal cancer cells. Live cell mitochondrial energy metabolism analysis was performed to detect changes in mitochondrial energy metabolism of the colorectal cancer cells, while western blot analysis was used to measure the expression of cytochrome c and autophagy‑related protein, LC3. RFP‑GFP‑LC3 lentivirus was used to detect autophagic flux, and autophagosomes were observed using a transmission electron microscope, while flow cytometry was used to analyze the effect of penicillin on cell cycle progression and apoptosis of the colorectal cancer cells. After penicillin treatment, the growth, migration and invasion ability of the colorectal cancer cells were inhibited. The mitochondrial energy metabolism of the cell was impaired, and the basic respiratory capacity, maximum respiratory capacity, respiratory potential, and ATP production were all reduced. The protein expression levels of the autophagy‑related proteins, LC3‑II/LC3‑I increased in a dose‑ and time‑dependent manner. In addition, autophagy flux and the number of autophagosomes increased, and mitochondrial structural damage was observed. The cell cycle was arrested at the G1 phase, the number of early apoptotic cells increased and the protein expression level of cleaved caspase‑3 increased, while penicillin‑induced apoptosis was blocked by the autophagy inhibitor 3‑MA. In conclusion, penicillin disrupted mitochondrial function and energy metabolism in the colorectal cancer cells, which resulted in the induction of autophagic apoptosis and ultimately the inhibition of cancer cell growth and metastasis.
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Copy and paste a formatted citation
Spandidos Publications style
Hu F, Wu Y, Liu C, Zhu Y, Ye S, Xi Y, Cui W and Bu S: Penicillin disrupts mitochondrial function and induces autophagy in colorectal cancer cell lines. Oncol Lett 22: 691, 2021.
APA
Hu, F., Wu, Y., Liu, C., Zhu, Y., Ye, S., Xi, Y. ... Bu, S. (2021). Penicillin disrupts mitochondrial function and induces autophagy in colorectal cancer cell lines. Oncology Letters, 22, 691. https://doi.org/10.3892/ol.2021.12952
MLA
Hu, F., Wu, Y., Liu, C., Zhu, Y., Ye, S., Xi, Y., Cui, W., Bu, S."Penicillin disrupts mitochondrial function and induces autophagy in colorectal cancer cell lines". Oncology Letters 22.4 (2021): 691.
Chicago
Hu, F., Wu, Y., Liu, C., Zhu, Y., Ye, S., Xi, Y., Cui, W., Bu, S."Penicillin disrupts mitochondrial function and induces autophagy in colorectal cancer cell lines". Oncology Letters 22, no. 4 (2021): 691. https://doi.org/10.3892/ol.2021.12952
Copy and paste a formatted citation
x
Spandidos Publications style
Hu F, Wu Y, Liu C, Zhu Y, Ye S, Xi Y, Cui W and Bu S: Penicillin disrupts mitochondrial function and induces autophagy in colorectal cancer cell lines. Oncol Lett 22: 691, 2021.
APA
Hu, F., Wu, Y., Liu, C., Zhu, Y., Ye, S., Xi, Y. ... Bu, S. (2021). Penicillin disrupts mitochondrial function and induces autophagy in colorectal cancer cell lines. Oncology Letters, 22, 691. https://doi.org/10.3892/ol.2021.12952
MLA
Hu, F., Wu, Y., Liu, C., Zhu, Y., Ye, S., Xi, Y., Cui, W., Bu, S."Penicillin disrupts mitochondrial function and induces autophagy in colorectal cancer cell lines". Oncology Letters 22.4 (2021): 691.
Chicago
Hu, F., Wu, Y., Liu, C., Zhu, Y., Ye, S., Xi, Y., Cui, W., Bu, S."Penicillin disrupts mitochondrial function and induces autophagy in colorectal cancer cell lines". Oncology Letters 22, no. 4 (2021): 691. https://doi.org/10.3892/ol.2021.12952
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