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Introduction
Colon carcinoma is one of the most common and aggressive malignant tumors worldwide (1). Currently, treatments for colon carcinoma are mainly surgery and chemotherapy, but the curative effect of existing chemotherapeutic drugs is not good, and they have numerous side-effects, including myelosuppression, neutropenia and thrombocytopenia (2). Therefore, the exploration of a new approach, such as novel drugs with specific effects on colon carcinoma treatment is urgently needed.
Harmine, a β-carboline alkaloid isolated from the seeds of Peganum harmala (Fig. 1), has been traditionally used for ritual and medicinal preparations in the Middle East, Central Asia and South America (3). Previous research has shown that harmine plays roles in anticancer treatments (4–6) and possesses anti-leishmanial properties (7) and antiviral effects (8) via inhibition of DYRK1A substrate phosphorylation. This compound was also found to interfere with neuritogenesis in cultured hippocampal neurons (9) and inhibit angiogenesis (10), telomerase activity (5) and mitochondrial signaling pathways (6,11), in addition to inducing DNA single- or double-strand breaks (12). It has been reported that harmine activates both the intrinsic and extrinsic pathways of apoptosis and regulates various transcription factors and pro-inflammatory cytokines in B16F-10 cells (6). Furthermore, the in vivo anti-angiogenic activity of harmine was studied using B16F-10 melanoma cells in C57BL/6 mice. The results showed that harmine decreased tumor capillary formation and inhibited angiogenesis (4). Harmine was also shown to induce apoptosis and suppress tumor cell proliferation through the downregulation of cyclooxygenase-2 expression in gastric cancer (13). Additionally, harmine can upregulate p21 and p27, enhance the formation of complexes with the G1-S phase CDKs and cyclins, and induce G1 arrest to stall cancer progression in human breast cancer MCF7 (p53 wild-type), MCF7 (p53 knockdown) and MDA-MB-468 (p53 mutant) cells (14). In cytotoxicity assays, harmine exhibited a strong inhibitory effect on the growth and proliferation of carcinoma cells, whereas it had no significant effects on quiescent fibroblasts (15). However, no detailed data are available in regards to the growth inhibition of human colon carcinoma cells. In the present study, we investigated the effect of harmine on the growth of human SW620 cells.
Materials and methods
Materials
Harmine was purchased from the Xi'an Feida Bio-Tech Co., Ltd. (Xi'an, China). Fetal bovine serum (FBS), RPMI-1640 medium, trypsin and EDTA were purchased from Gibco-BRL...