Kim Aeyung, Im Minju, Yim Nam-Hiu, Hwang Youn-Hwan, Yang Hye Jin, Ma Jin Yeul
Korean Medicine (KM)-Based Herbal Drug Development Group, Korea Institute of Oriental Medicine (KIOM), Daejeon 305-811, Republic of Korea.
Oncol Rep. 2015 Aug;34(2):900-12. doi: 10.3892/or.2015.4018. Epub 2015 May 29.
MA128, a novel herbal medicine, was previously identified and its effectiveness in the treatment of asthma and atopic dermatitis (AD) was demonstrated. In particular, post-inflammatory hyperpigmentation (PIH) in AD mice was improved by treatment with MA128. In addition, MA128 exhibited anti-melanogenic activity by inhibiting tyrosinase activity via the p38 MAPK and protein kinase A signaling pathways in B16F10 cells. In the present study, we examined whether oral administration of MA128 suppressed the in vivo tumor growth of HT1080 cells in athymic nude mice. The results showed that the daily oral administration of 75 and 150 mg/kg MA128 suppressed the tumorigenic growth of HT1080 cells efficiently. Since metastasis is a major cause of cancer-associated mortality and the greatest challenge during cancer treatment, we investigated the effect of non-toxic concentrations of MA128 on the metastatic potential of HT1080 cells. MA128 inhibited anchorage-independent colony formation, migration and invasion. Matrix metalloproteinase-9 (MMP-9) activity under resting and PMA-stimulated conditions was decreased in a dose-dependent manner by MA128 in HT1080 cells. In addition, the daily oral administration of MA128 at doses of 75 and 150 mg/kg efficiently blocked the lung metastasis of B16F10 cells that had been injected into the tail veins of C57BL/6 mice. In particular, none of the mice treated with MA128 exhibited systemic toxicity, such as body weight loss or liver and kidney dysfunction. MA128 also inhibited tumor‑induced angiogenesis. Taken together, the results suggest that MA128 is a potential therapeutic agent and a safe herbal medicine for controlling malignant and metastatic cancer.
新型草药MA128先前已被鉴定出来，并证实其对哮喘和特应性皮炎（AD）具有治疗效果。特别是，MA128治疗可改善AD小鼠的炎症后色素沉着（PIH）。此外，MA128通过在B16F10细胞中经由p38丝裂原活化蛋白激酶（MAPK）和蛋白激酶A信号通路抑制酪氨酸酶活性，从而表现出抗黑色素生成活性。在本研究中，我们检测了口服MA128是否能抑制无胸腺裸鼠体内HT1080细胞的肿瘤生长。结果显示，每日口服75和150 mg/kg的MA128能有效抑制HT1080细胞的致瘤性生长。由于转移是癌症相关死亡的主要原因以及癌症治疗期间最大的挑战，我们研究了无毒浓度的MA128对HT1080细胞转移潜能的影响。MA128抑制非锚定依赖性集落形成、迁移和侵袭。在HT1080细胞中，MA128以剂量依赖性方式降低了静息和佛波酯（PMA）刺激条件下基质金属蛋白酶-9（MMP-9）的活性。此外，每日口服75和150 mg/kg剂量的MA128能有效阻断已注射到C57BL/6小鼠尾静脉中的B16F10细胞的肺转移。特别是，接受MA128治疗的小鼠均未表现出全身毒性，如体重减轻或肝肾功能障碍。MA128还抑制肿瘤诱导的血管生成。综上所述，结果表明MA128是一种控制恶性和转移性癌症的潜在治疗药物和安全的草药。
