Abstract
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Cancer stem cells (CSCs) are a rare population with self-renewal and multipotent differentiation capacity, and reside among the more differentiated cancer cells. CSCs are associated with tumor recurrence, drug resistance and poor prognosis. The aim of this study was to determine the efficacy of napabucasin against HCC and elucidate the underlying molecular mechanisms. Napabucasin significantly decreased the viability of HCC cells in vitro by inducing apoptosis and cell cycle arrest. In addition, it suppressed CSC-related gene expression and spheroid formation in vitro, indicating depletion of CSCs. The anti-neoplastic effects of napabucasin was also evident in homograft tumor-bearing mouse models. Our findings provide the scientific basis of conducting clinical trials on napabucasin as a new therapeutic agent against HCC.
Highlights
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, and chronic liver diseases and cirrhosis are its underlying pathologies
The potential cytotoxic effect of napabucasin on HCC cells was evaluated in terms of the proliferation ability of multiple human and murine HCC cell lines, and compared to that of oxaliplatin and the plant-derived Signal transducer and activator of transcription 3 (STAT3) inhibitor cryptotanshinone (Liu et al, 2017; Qin et al, 2017; Ji et al, 2019; Zhu et al, 2019)
The apoptosis rates in Huh7 cells increased to 11.11%, 14.38% and 62.99% respectively within 12 h of exposure to 1, 2 and 5 μM napabucasin (Figure 2C), and similar results were obtained with Hepa1-6 cells as well
Summary
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, and chronic liver diseases and cirrhosis are its underlying pathologies. The annual mortality rate of liver cancer is 700,000 worldwide, and the number of newly diagnosed HCC is estimated to increase further in the coming decades (Balogh et al, 2016; Rawla et al, 2018; Asrani et al, 2019). Since it is asymptomatic in the early stages, HCC is usually diagnosed in its advanced stage, which precludes the possibility of surgical resection (Daher et al, 2018). Cancer stem cells (CSCs) are a rare subpopulation of tumor cells that have the capacity to selfrenew and differentiate into multiple lineages. Preventing liver CSCs formation is a viable therapeutic strategy against HCC
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