Lin Weiting, Li Yizhen, Huang Hsinyi, Zhao Peiwen, Su Yining, Fang Chiung-Yao
Department of Stomatology, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi 600, Taiwan, R.O.C.
Department of Medical Research, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi 600, Taiwan, R.O.C.
Exp Ther Med. 2025 Apr 4;29(6):111. doi: 10.3892/etm.2025.12861. eCollection 2025 Jun.
Oral squamous cell carcinoma (OSCC) represents the most frequently occurring form of oral cancer. However, despite the availability of advanced treatment modalities, the global 5-year survival rate for patients with advanced OSCC remains at ~50-60%. Devising alternative therapeutic strategies for oral cancer has therefore become an urgent need. Harmine, a β-carboline alkaloid, has recently been shown to exhibit anticancer activity. Compared with harmine, harmine hydrochloride (HH), a derivative of harmine, has improved water solubility and stability, so can absorb into tissues more readily. Therefore, the present study aimed to investigate the anticancer activity of HH in OSCC cells. A Cell Counting Kit-8 assay was performed to assess the cytotoxic effects of HH on the OSCC cell lines, SCC-4 and SCC-25. Flow cytometric analysis was subsequently employed to examine both the cell cycle profile and the extent of apoptosis. Western blotting was used to assess the expression levels of the regulatory proteins involved in these biological activities, and treatment with a pan-caspase inhibitor (Z-VAD-FMK) confirmed the involvement of the apoptotic pathway. Furthermore, western blotting was used to investigate which signaling pathways were affected in the HH-treated cells. Taken together, the findings of the present study demonstrated that HH was cytotoxic in OSCC cells. HH treatment induced G0/G1 phase cell cycle arrest and apoptosis. Additionally, the MAPK pathway was shown to be involved in HH-induced apoptosis in SCC-4 cells. Therefore, HH exhibited anticancer activity, and may be a putative therapeutic agent for the treatment of OSCC in the future.
口腔鳞状细胞癌（OSCC）是口腔癌中最常见的形式。然而，尽管有先进的治疗方式，但晚期OSCC患者的全球5年生存率仍保持在约50%-60%。因此，为口腔癌设计替代治疗策略已成为迫切需求。哈尔明，一种β-咔啉生物碱，最近已被证明具有抗癌活性。与哈尔明相比，哈尔明盐酸盐（HH）作为哈尔明的衍生物，具有更好的水溶性和稳定性，因此能更易被组织吸收。因此，本研究旨在探究HH对OSCC细胞的抗癌活性。进行细胞计数试剂盒-8检测以评估HH对OSCC细胞系SCC-4和SCC-25的细胞毒性作用。随后采用流式细胞术分析来检测细胞周期分布和凋亡程度。蛋白质免疫印迹法用于评估参与这些生物学活性的调节蛋白的表达水平，并用泛半胱天冬酶抑制剂（Z-VAD-FMK）处理以证实凋亡途径的参与。此外，蛋白质免疫印迹法用于研究在HH处理的细胞中哪些信号通路受到影响。综上所述，本研究结果表明HH对OSCC细胞具有细胞毒性。HH处理诱导G0/G1期细胞周期阻滞和凋亡。此外，丝裂原活化蛋白激酶（MAPK）通路被证明参与了HH诱导的SCC-4细胞凋亡。因此，HH具有抗癌活性，可能是未来治疗OSCC的一种潜在治疗药物。
