Ono Motoki, Miyamoto Tsutomu, Fuseya Chiho, Asaka Ryoichi, Ando Hirofumi, Tanaka Yasuhiro, Shinagawa Manaka, Yokokawa Yusuke, Takeuchi Hodaka, Horiuchi Akiko, Shiozawa Tanri
Department of Obstetrics and Gynecology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan.
Horiuchi Ladies Clinic, 1-16-3 Tsukama, Matsumoto, 390-0821, Japan.
Discov Oncol. 2023 Jan 23;14(1):9. doi: 10.1007/s12672-023-00617-2.
Wasabi is a traditional plant seasoning with an anti-septic function. Recent studies revealed several functions of Wasabi, such as anti-inflammation; however, the anti-tumor effect against endometrial carcinoma (EMC) cells has not been examined. In the present study, we investigated the anti-tumor effect of 6-(methylsulfinyl) hexyl isothiocyanate (6-MITC), a major chemical compound of Wasabi, against various EMC cell lines in vitro and in vivo.
The effect of 6-MITC on cell viability was measured by the WST-1 assay in EMC and HUVEC cells. The impact of 6-MITC oral administration in nude mice was measured to assess the growth of the EMC xenograft and natural killer (NK) cell activity in the spleen.
The addition of 6-MITC suppressed the proliferation of EMC cells (Ishikawa, HEC265, HEC108, KLE, and HEC1B) dose-dependently, but not HUVEC cells. 6-MITC (5 µM) enhanced the cisplatin sensitivity of EMC cells. 6-MITC induced apoptosis in a dose-dependent fashion in EMC cells other than HEC1B cells and was associated with increased expression of cleaved-caspase3 and decreased expression of BCL2. Oral administration of 6-MITC (2 and 4 µmol/kg) to Ishikawa and HEC1B xenografting mice resulted in a reduced tumor volume compared with the control (P < 0.05, 4 µmol/kg). Immunohistochemical staining of resected tumors revealed increased expression of Ki-67 and reduced cleaved-caspase3. Furthermore, 6-MITC treatment enhanced NK cell activity, especially when administered before tumor xenografting.
These results indicate that 6-MITC has a marked anti-tumor effect against EMC cells and a novel effect to enhance NK cell activity. These effects suggest the therapeutic potential of 6-MITC.
山葵是一种具有抗菌功能的传统植物调味料。最近的研究揭示了山葵的几种功能，如抗炎作用；然而，其对子宫内膜癌（EMC）细胞的抗肿瘤作用尚未得到研究。在本研究中，我们调查了山葵的主要化学成分异硫氰酸6-（甲基亚磺酰基）己酯（6-MITC）对多种EMC细胞系在体外和体内的抗肿瘤作用。
采用WST-1法检测6-MITC对EMC细胞和人脐静脉内皮细胞（HUVEC）活力的影响。通过测量6-MITC口服给药对裸鼠EMC异种移植物生长和脾脏自然杀伤（NK）细胞活性的影响来评估其作用。
添加6-MITC可剂量依赖性地抑制EMC细胞（石川细胞、HEC265、HEC108、KLE和HEC1B）的增殖，但对HUVEC细胞无此作用。6-MITC（5 μM）可增强EMC细胞对顺铂的敏感性。6-MITC以剂量依赖性方式诱导除HEC1B细胞外的EMC细胞凋亡，并与裂解型半胱天冬酶3表达增加和BCL2表达降低有关。对石川细胞和HEC1B异种移植小鼠口服6-MITC（2和4 μmol/kg），与对照组相比，肿瘤体积减小（P < 0.05，4 μmol/kg）。对切除肿瘤的免疫组织化学染色显示，Ki-67表达增加，裂解型半胱天冬酶3表达减少。此外，6-MITC治疗可增强NK细胞活性，尤其是在肿瘤异种移植前给药时。
这些结果表明，6-MITC对EMC细胞具有显著的抗肿瘤作用，并具有增强NK细胞活性的新作用。这些作用提示了6-MITC的治疗潜力。
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