A Novel mTOR Inhibitor; Anthracimycin for the Treatment of Human Hepatocellular Carcinoma

作者：Hayashi Tomoyuki; Yamashita Taro; Okada Hikari; Oishi Naoki; Sunagozaka Hajime; Nio Kouki; Hayashi Takehiro; Hara Yasumasa; Asahina Yoshiro; Yoshida Mariko; Hashiba Tomomi; Suda Tsuyoshi; Shirasaki Takayoshi; Igarashi Yasuhiro; Miyanouchi Koji; Yamashita Tatsuya; Honda Masao; Kaneko Shuichi

来源：Anticancer Research, 2017, 37(7): 3397-3403.

DOI：10.21873/anticanres.11706

• Anthracimycin
• cancer stem cells
• hepatocellular carcinoma
• mammalian target of rapamycin

Background/Aim: Anthracimycin, a secondary metabolite of Streptomyces, has been shown to inhibit the invasion of certain cancer cell lines. Materials and Methods: In this study we evaluated the effect of anthracimycin on cell growth and signaling pathways in hepatocellular carcinoma (HCC). Results: Anthracimycin suppressed cell proliferation and motility and induced apoptosis in human HCC cell lines. Furthermore, anthracimycin had no effect on the enrichment of EpCAM-high liver cancer stem cells (CSCs), while fluorouracil dramatically enriched the CSCs with activation of the stemness-related genes EPCAM and SOX9 in HuH7 cells. Mechanistically, anthracimycin suppressed mammalian target of rapamycin (mTOR) signaling, and was most effective at inhibiting HCC cell proliferation with mTOR activation. Conclusion: Anthracimycin is a novel mTOR inhibitor capable of suppressing the proliferation of CSCs and non-CSCs equally well in HCC, and it is suggested that anthracimycin could be effective in the eradication of HCC associated with mTOR-signaling activation.

• 出版日期2017-7