1. Academic Validation
  2. β,β-Dimethylacrylalkannin, a Natural Naphthoquinone, Inhibits the Growth of Hepatocellular Carcinoma Cells by Modulating Tumor-Associated Macrophages

β,β-Dimethylacrylalkannin, a Natural Naphthoquinone, Inhibits the Growth of Hepatocellular Carcinoma Cells by Modulating Tumor-Associated Macrophages

  • Molecules. 2024 Aug 20;29(16):3919. doi: 10.3390/molecules29163919.
Li-Sha Shen 1 2 Zesi Lin 3 Rui-Hong Gong 4 Yu-Shan Lin 5 Xing-Fang Qiao 1 2 Qian-Mei Hu 1 2 Wei-Han Qin 1 2 Sibao Chen 4 5 6 Yong Yang 1 2 Guo-Qing Chen 4 5 6
Affiliations

Affiliations

  • 1 Chongqing Academy of Chinese Materia Medica, Chongqing 400065, China.
  • 2 Sichuan-Chongqing Joint Key Laboratory of Innovation of New Drugs of Traditional Chinese Medicine, Chongqing 400065, China.
  • 3 Southern Medical University of Hospital of Integrated Traditional Chinese Medicine and Western Medicine, Southern Medical University, Guangzhou 510515, China.
  • 4 Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Hung Hom, Hong Kong 999077, China.
  • 5 State Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen 518057, China.
  • 6 Research Centre for Chinese Medicine Innovation, The Hong Kong Polytechnic University, Hung Hom, Hong Kong 999077, China.
Abstract

Tumor-associated macrophages (TAMs) are pivotal in the tumor microenvironment (TME) of hepatocellular carcinoma (HCC), influencing various stages from initiation to metastasis. Understanding the role of TAMs in HCC is crucial for developing novel therapeutic strategies. Macrophages exhibit plasticity, resulting in M1 and M2 phenotypes, with M1 macrophages displaying antitumor properties and M2 macrophages promoting tumor progression. Targeting TAMs to alter their polarization could offer new avenues for HCC treatment. β,β-dimethylacrylalkannin (DMAKN), a natural naphthoquinone, has gained attention for its antitumor properties. However, its impact on TAMs modulation remains unclear. This study investigates DMAKN's modulation of TAMs and its anti-HCC activity. Using an in vitro model with THP-1 cells, we induced M1 macrophages with LPS/IFN-γ and M2 macrophages with IL-4/IL-13, confirming polarization with specific markers. Co-culturing these macrophages with HCC cells showed that M1 cells inhibited HCC growth, while M2 cells promoted it. Screening for non-toxic DMAKN concentrations revealed its ability to induce M1 polarization and enhance LPS/IFN-γ-induced M1 macrophages, both showing anti-HCC effects. Conversely, DMAKN suppressed IL-4/IL-13-induced M2 polarization, inhibiting M2 macrophages' promotion of HCC cell viability. In summary, DMAKN induces and enhances M1 polarization while inhibiting M2 polarization of macrophages, thereby inhibiting HCC cell growth. These findings suggest that DMAKN has the potential to regulate TAMs in HCC, offering promise for future therapeutic development.

Keywords

THP-1; co-culture; hepatocellular carcinoma; macrophage polarization; β,β-dimethylacrylalkannin.

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