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Anticancer effects of Poncirus fructus on hepatocellular carcinoma through regulation of apoptosis, migration, and invasion

  • Authors:
    • Suvesh Munakarmi
    • Lokendra Chand
    • Hyun Beak Shin
    • Usama Khamis Hussein
    • Bong‑Sik Yun
    • Hae Ryong Park
    • Yeon Jun Jeong
  • View Affiliations / Copyright

    Affiliations: Laboratory of Liver Regeneration, Biomedical Research Institute, Chonbuk National University Medical School, Jeonju 54907, Republic of Korea, Research Institute of Clinical Medicine of Jeonbuk National University, Biomedical Research Institute of Chonbuk National University, Jeonju 54907, Republic of Korea, Division of Biotechnology, College of Environmental and BioSource Sciences, Chonbuk National University, Jeonju 54907, Republic of Korea, Department of Food Science and Biotechnology, Kyungnam University, Masanhappo‑gu, Changwon‑si 631‑701, Republic of Korea
    Copyright: © Munakarmi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2537-2546
    |
    Published online on: October 5, 2020
       https://doi.org/10.3892/or.2020.7790
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Abstract

Poncirus fructus (PF) is a phytochemical compound extracted from the dry, immature fruits of Poncirus trifoliate. PF is traditionally used to treat gastrointestinal disorders, allergies, and inflammatory disease. In East Asia, PF is also known for its anticancer properties. There are numerous reports on the anticancer and anti‑inflammatory effects of PF in a wide range of cancers and gastrointestinal diseases, respectively. However, the role of PF in inducing apoptosis and suppressing the invasiveness of hepatocellular carcinoma (HCC) remains unclear. This study investigated the ability of PF to induce apoptosis and inhibit the invasiveness and migratory ability of HCC cell lines (Hep3B and Huh7). Wound healing, Transwell migration and invasion, and colony‑formation assays, as well as flow cytometry, were used to analyze cell proliferation, migration, invasion, and apoptosis. Epithelial‑mesenchymal transition (EMT)‑related and apoptotic proteins were assessed by western blotting. The mitochondrial membrane potential of the Hep3B and Huh7 cells was observed with tetramethylrhodamine ethyl ester. The reactive oxygen species (ROS) level was determined by dihydroethidium (DHE) staining. PF treatment significantly decreased the proliferation of Hep3B and Huh7 cells in a dose‑dependent manner, reduced the mitochondrial membrane potential, increased ROS levels, decreased the protein levels of Bcl‑2, and increased the protein levels of Bax and cleaved caspase‑3 and 9, suggesting that PF mediated HCC apoptosis via a mitochondrial pathway. Our findings showed that PF prevented HCC cell migration and invasion by inhibiting the EMT process and downregulating MMP‑2 and MMP‑9 activities. The results suggest the potential anticancer effects of PF by inhibiting proliferation, inducing apoptosis, and reducing the invasion and migration of HCC cells.
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Copy and paste a formatted citation
Spandidos Publications style
Munakarmi S, Chand L, Shin HB, Hussein UK, Yun BS, Park HR and Jeong YJ: Anticancer effects of Poncirus fructus on hepatocellular carcinoma through regulation of apoptosis, migration, and invasion. Oncol Rep 44: 2537-2546, 2020.
APA
Munakarmi, S., Chand, L., Shin, H.B., Hussein, U.K., Yun, B., Park, H.R., & Jeong, Y.J. (2020). Anticancer effects of Poncirus fructus on hepatocellular carcinoma through regulation of apoptosis, migration, and invasion. Oncology Reports, 44, 2537-2546. https://doi.org/10.3892/or.2020.7790
MLA
Munakarmi, S., Chand, L., Shin, H. B., Hussein, U. K., Yun, B., Park, H. R., Jeong, Y. J."Anticancer effects of Poncirus fructus on hepatocellular carcinoma through regulation of apoptosis, migration, and invasion". Oncology Reports 44.6 (2020): 2537-2546.
Chicago
Munakarmi, S., Chand, L., Shin, H. B., Hussein, U. K., Yun, B., Park, H. R., Jeong, Y. J."Anticancer effects of Poncirus fructus on hepatocellular carcinoma through regulation of apoptosis, migration, and invasion". Oncology Reports 44, no. 6 (2020): 2537-2546. https://doi.org/10.3892/or.2020.7790
Copy and paste a formatted citation
x
Spandidos Publications style
Munakarmi S, Chand L, Shin HB, Hussein UK, Yun BS, Park HR and Jeong YJ: Anticancer effects of Poncirus fructus on hepatocellular carcinoma through regulation of apoptosis, migration, and invasion. Oncol Rep 44: 2537-2546, 2020.
APA
Munakarmi, S., Chand, L., Shin, H.B., Hussein, U.K., Yun, B., Park, H.R., & Jeong, Y.J. (2020). Anticancer effects of Poncirus fructus on hepatocellular carcinoma through regulation of apoptosis, migration, and invasion. Oncology Reports, 44, 2537-2546. https://doi.org/10.3892/or.2020.7790
MLA
Munakarmi, S., Chand, L., Shin, H. B., Hussein, U. K., Yun, B., Park, H. R., Jeong, Y. J."Anticancer effects of Poncirus fructus on hepatocellular carcinoma through regulation of apoptosis, migration, and invasion". Oncology Reports 44.6 (2020): 2537-2546.
Chicago
Munakarmi, S., Chand, L., Shin, H. B., Hussein, U. K., Yun, B., Park, H. R., Jeong, Y. J."Anticancer effects of Poncirus fructus on hepatocellular carcinoma through regulation of apoptosis, migration, and invasion". Oncology Reports 44, no. 6 (2020): 2537-2546. https://doi.org/10.3892/or.2020.7790
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