The Natural Pigment Violacein Potentially Suppresses the Proliferation and Stemness of Hepatocellular Carcinoma Cells In Vitro
Hepatocellular carcinoma (HCC) is a malignant type of primary liver cancer with high incidence and mortality, worldwide. A major challenge in the treatment of HCC is chemotherapeutic resistance. It is therefore necessary to develop novel anticancer drugs for suppressing the growth of HCC cells and o...
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MDPI AG
2021-10-01
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| author | Yu Jin Kim Nayeong Yuk Hee Jeong Shin Hye Jin Jung |
| author_facet | Yu Jin Kim Nayeong Yuk Hee Jeong Shin Hye Jin Jung |
| author_sort | Yu Jin Kim |
| collection | DOAJ |
| description | Hepatocellular carcinoma (HCC) is a malignant type of primary liver cancer with high incidence and mortality, worldwide. A major challenge in the treatment of HCC is chemotherapeutic resistance. It is therefore necessary to develop novel anticancer drugs for suppressing the growth of HCC cells and overcoming drug resistance for improving the treatment of HCC. Violacein is a deep violet-colored indole derivative that is produced by several bacterial strains, including <i>Chromobacterium violaceum</i>, and it possesses numerous pharmacological properties, including antitumor activity. However, the therapeutic effects of violacein and the mechanism underlying its antitumor effect against HCC remain to be elucidated. This study is the first to demonstrate that violacein inhibits the proliferation and stemness of Huh7 and Hep3B HCC cells. The antiproliferative effect of violacein was attributed to cell cycle arrest at the sub-G1 phase and the induction of apoptotic cell death. Violacein induced nuclear condensation, dissipated mitochondrial membrane potential (MMP), increased generation of reactive oxygen species (ROS), activated the caspase cascade, and upregulated p53 and p21. The anticancer effect of violacein on HCC cells was also associated with the downregulation of protein kinase B (AKT) and extracellular signal-regulated kinase (ERK)1/2 signaling. Violacein not only suppressed the proliferation and formation of tumorspheres of Huh7 and Hep3B cancer stem-like cells but also reduced the expression of key markers of cancer stemness, including CD133, Sox2, Oct4, and Nanog, by inhibiting the signal transducer and activator of transcription 3 (STAT3)/AKT/ERK pathways. These results suggest the therapeutic potential of violacein in effectively suppressing HCC by targeting the proliferation and stemness of HCC cells. |
| first_indexed | 2024-03-10T06:59:22Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T06:59:22Z |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e3bed64d3de248c69a1be395d86d558f2023-11-22T16:14:29ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-10-0122191073110.3390/ijms221910731The Natural Pigment Violacein Potentially Suppresses the Proliferation and Stemness of Hepatocellular Carcinoma Cells In VitroYu Jin Kim0Nayeong Yuk1Hee Jeong Shin2Hye Jin Jung3Department of Life Science and Biochemical Engineering, Sun Moon University, Asan 31460, KoreaDepartment of Pharmaceutical Engineering and Biotechnology, Sun Moon University, Asan 31460, KoreaDepartment of Life Science and Biochemical Engineering, Sun Moon University, Asan 31460, KoreaDepartment of Life Science and Biochemical Engineering, Sun Moon University, Asan 31460, KoreaHepatocellular carcinoma (HCC) is a malignant type of primary liver cancer with high incidence and mortality, worldwide. A major challenge in the treatment of HCC is chemotherapeutic resistance. It is therefore necessary to develop novel anticancer drugs for suppressing the growth of HCC cells and overcoming drug resistance for improving the treatment of HCC. Violacein is a deep violet-colored indole derivative that is produced by several bacterial strains, including <i>Chromobacterium violaceum</i>, and it possesses numerous pharmacological properties, including antitumor activity. However, the therapeutic effects of violacein and the mechanism underlying its antitumor effect against HCC remain to be elucidated. This study is the first to demonstrate that violacein inhibits the proliferation and stemness of Huh7 and Hep3B HCC cells. The antiproliferative effect of violacein was attributed to cell cycle arrest at the sub-G1 phase and the induction of apoptotic cell death. Violacein induced nuclear condensation, dissipated mitochondrial membrane potential (MMP), increased generation of reactive oxygen species (ROS), activated the caspase cascade, and upregulated p53 and p21. The anticancer effect of violacein on HCC cells was also associated with the downregulation of protein kinase B (AKT) and extracellular signal-regulated kinase (ERK)1/2 signaling. Violacein not only suppressed the proliferation and formation of tumorspheres of Huh7 and Hep3B cancer stem-like cells but also reduced the expression of key markers of cancer stemness, including CD133, Sox2, Oct4, and Nanog, by inhibiting the signal transducer and activator of transcription 3 (STAT3)/AKT/ERK pathways. These results suggest the therapeutic potential of violacein in effectively suppressing HCC by targeting the proliferation and stemness of HCC cells.https://www.mdpi.com/1422-0067/22/19/10731violaceinhepatocellular carcinomaproliferationapoptosisstemness |
| spellingShingle | Yu Jin Kim Nayeong Yuk Hee Jeong Shin Hye Jin Jung The Natural Pigment Violacein Potentially Suppresses the Proliferation and Stemness of Hepatocellular Carcinoma Cells In Vitro International Journal of Molecular Sciences violacein hepatocellular carcinoma proliferation apoptosis stemness |
| title | The Natural Pigment Violacein Potentially Suppresses the Proliferation and Stemness of Hepatocellular Carcinoma Cells In Vitro |
| title_full | The Natural Pigment Violacein Potentially Suppresses the Proliferation and Stemness of Hepatocellular Carcinoma Cells In Vitro |
| title_fullStr | The Natural Pigment Violacein Potentially Suppresses the Proliferation and Stemness of Hepatocellular Carcinoma Cells In Vitro |
| title_full_unstemmed | The Natural Pigment Violacein Potentially Suppresses the Proliferation and Stemness of Hepatocellular Carcinoma Cells In Vitro |
| title_short | The Natural Pigment Violacein Potentially Suppresses the Proliferation and Stemness of Hepatocellular Carcinoma Cells In Vitro |
| title_sort | natural pigment violacein potentially suppresses the proliferation and stemness of hepatocellular carcinoma cells in vitro |
| topic | violacein hepatocellular carcinoma proliferation apoptosis stemness |
| url | https://www.mdpi.com/1422-0067/22/19/10731 |
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