Bioassay-Guided Discovery of Potential Partial Extracts with Cytotoxic Effects on Liver Cancer Cells from Vietnamese Medicinal Herbs

Hepatocellular carcinoma (HCC) is the most frequent type of primary liver cancer and is the leading cause of cancer mortality in Vietnam. Our study aims to discover the partial extracts with the potential cytotoxic effects on HCC cells from the different parts of 24 Vietnamese medicinal plants traditionally used in liver cancer treatment. Out of 52 crude methanol extracts, we found that Luvunga scandens leaves, Hyptis suaveolens roots, and Solanum torvum leaves showed the notable cytotoxic effects against HCC cells. After that, we carried out partial extract of the three methanol extracts with ethyl acetate, water, n-hexane, and 90% methanol. The cytotoxic activity on Huh-7 HCC cells, antioxidant capacity, and total flavonoids content (TFC) of each partial extraction were determined. Methanol, ethyl acetate, and 90% methanol extracts showed moderate to strong cytotoxicity activity against Huh-7 HCC cells. Notably, the ethyl acetate and 90% methanol extract from H. suaveolens roots with high TFC values and strong antioxidant capacity could be promising sources of novel therapeutic modalities for HCC treatment. For the leaves of L. scandens and S. torvum, the ethyl acetate extract showed high TFC value and promising anti-HCC activity, therefore recommended further studies.

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Long non-coding RNA MALAT1 promotes angiogenesis and immunosuppressive properties of HCC cells by sponging miR-140

AJP Cell Physiology ◽

10.1152/ajpcell.00510.2018 ◽

2020 ◽

Vol 318 (3) ◽

pp. C649-C663 ◽

Cited By ~ 12

Author(s):

Zhou-Hua Hou ◽

Xu-Wen Xu ◽

Xiao-Yu Fu ◽

Le-Du Zhou ◽

Shui-Ping Liu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cancer ◽

Regulatory Network ◽

Primary Liver Cancer ◽

Underlying Mechanism ◽

In Vivo Studies ◽

Non Coding Rna ◽

Long Non Coding Rna ◽

Hcc Cells

Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer in adults. Previous studies in our laboratory found that long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was upregulated in HCC cells, which could affect the metastasis and invasion of HCC. However, the underlying mechanism remains unknown. Herein, we studied the interaction between MALAT1 and miR-140 on the regulation of angiogenesis and immunosuppressive properties. We revealed that the expression of MALAT1 and VEGF-A was significantly increased in HCC cells. Knockdown of MALAT1 in HCC cells suppressed the production of VEGF-A, impaired the angiogenesis of HUVECs, and facilitated the polarization of macrophage toward the M1 subset. Mechanistically, the interaction between MALAT1 and miR-140 or between miR-140 and VEGF-A was confirmed by multiple assays. Besides, a negative correlation between MALAT1 and miR-140 was found in HCC tissues. Furthermore, miR-140 inhibition significantly increased VEGF-A expression, promoted angiogenesis of HUVECs, and redirected the polarization of macrophages toward the M2 subset. In addition, in vivo studies also verified the regulatory network of the MALAT1/miR-140 axis on VEGF-A in HCC progression. In summary, this study revealed the mechanism that MALAT1 worked as a putative HCC promotor via inhibiting miR-140. Therefore, targeting MALAT1 or miR-140 might alleviate the progression of HCC in the future.

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TGF-β1 Induces Immune Escape by Enhancing PD-1 and CTLA-4 Expression on T Lymphocytes in Hepatocellular Carcinoma

Frontiers in Oncology ◽

10.3389/fonc.2021.694145 ◽

2021 ◽

Vol 11 ◽

Author(s):

Shixiang Bao ◽

Xiaopei Jiang ◽

Shuai Jin ◽

Peipei Tu ◽

Jingtao Lu

Keyword(s):

Hepatocellular Carcinoma ◽

T Cells ◽

T Lymphocytes ◽

Liver Cancer ◽

Transforming Growth Factor ◽

Immune Escape ◽

Primary Liver Cancer ◽

Activated T Cells ◽

Tgf Β1 ◽

Hcc Cells

Primary liver cancer (PLC) is one of the most common types of cancer worldwide. Hepatocellular carcinoma (HCC) accounts for approximately 90% of PLC cases. The HCC microenvironment plays an important role in the occurrence and development of HCC. Immunotherapy for the HCC microenvironment has become an effective treatment strategy. T lymphocytes are an important part of the HCC microenvironment, and programmed cell death 1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) are the main immunosuppressive molecules of T lymphocytes. Transforming growth factor β1 (TGF-β1) can inhibit the immune function of T lymphocytes and promote the occurrence and development of tumors. However, few studies have explored whether TGF-β1 can upregulate the expression of PD-1 and CTLA-4 on T cells. In this study, we showed that TGF-β1 upregulated the expression of PD-1 and CTLA-4 on T lymphocytes and attenuated the cytotoxicity of T lymphocytes for HCC cells in vitro and in vivo. In addition, TGF-β1 increased the apoptosis of T lymphocytes induced by HCC cells. Finally, we found that the mechanism by which TGF-β1 upregulates the expression of PD-1 and CTLA-4 on T lymphocytes may be related to the calcineurin-nuclear factor of activated T cells 1 (CaN/NFATc1) pathway. This study will provide some experimental basis for liver cancer immunotherapy based on the tumor microenvironment.

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