The anti-liver cancer effect of water extract of the aerial part of G. divaricata (GD extract) was evaluated. A moderate cytotoxicity of GD extract in liver cancer cells was observed. GD extract sensitized Huh7 cells to cisplatin and 5-fluorouracil. Interestingly, GD extract inhibited cancer sphere formation and reduced the expression of cancer stem cell (CSC) markers. Importantly, GD extract suppressed Huh7 tumor growth and prolong the anti-liver cancer effect of cisplatin in vivo. Treatment of GD extract resulted in reductions of Wnt reporter activity and the expression of Wnt target genes.

Liver cancer is the sixth common cancer and the second leading cause of cancer death worldwide. Despite the available treatment options, liver cancer remains the second leading cause of cancer death globally and the treatment outcome for patients have not been satisfactory. Gynura divaricata (L.) DC. ssp. formosana is widely used folk herbal medicine for treating diabetes and hepatitis. The anti-liver cancer effect of water extract of the aerial part of G. divaricata (GD extract) was evaluated. A moderate cytotoxicity of GD extract in liver cancer cells was observed. GD extract sensitized Huh7 cells to cisplatin and 5-fluorouracil. Interestingly, GD extract inhibited cancer sphere formation and reduced the expression of cancer stem cell (CSC) markers. Importantly, GD extract suppressed Huh7 tumor growth and prolong the anti-liver cancer effect of cisplatin in vivo. Treatment of GD extract resulted in reductions of Wnt reporter activity and the expression of Wnt target genes. Moreover, suppression of β-catenin were observed in both GD extract treated Huh7 spheres and xenograft tumors. Surprisingly, the body weight loss was recovered faster in the cis and GD extract combination group than cis only group. Accordingly, our findings suggested that G. divaricata could target liver CSC via suppressing Wnt pathway and be a functional food with therapeutic benefit for HCC patients.

肝癌是全世界第六常見的癌症，卻是全球癌症死因的第三名，全球每年約70萬人被新診斷罹患肝癌，美國約有4萬人為新增病例，而中國更是全球肝癌發病率最高和死亡數最多的國家。肝癌藥物全球市場的年複合成長率（CAGR）達7到15%，屬於未被滿足的醫療需求（Unmet Medical Need）領域，具有高度開發價值