Open Access

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

  • Published online on: October 5, 2020     https://doi.org/10.3892/or.2020.7790
  • Pages: 2537-2546
  • Copyright: © Munakarmi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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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December-2020
Volume 44 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

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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