School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China.
Int J Mol Sci. 2019 Apr 18;20(8):1917. doi: 10.3390/ijms20081917.
Natural products, explicitly medicinal plants, are an important source of inspiration of antitumor drugs, because they contain astounding amounts of small molecules that possess diversifying chemical entities. For instance, (formerly ), a genus of the Lamiaceae (formerly Labiatae) family, has been reported as a rich source of natural diterpenes. In the current study, we evaluated the in vitro anti-proliferative property of flexicaulin A (FA), an diterpenoid with an -kaurane structure, in human carcinoma cells, by means of cell viability assay, flow cytometric assessment, quantitative polymerase chain reaction array, Western blotting analysis, and staining experiments. Subsequently, we validated the in vivo antitumor efficacy of FA in a xenograft mouse model of colorectal carcinoma. From our experimental results, FA appears to be a potent antitumor molecule, since it significantly attenuated the proliferation of human colorectal carcinoma cells in vitro and restricted the growth of corresponsive xenograft tumors in vivo without causing any adverse effects. Regarding its molecular mechanism, FA considerably elevated the expression level of p21 and induced cell cycle arrest in the human colorectal carcinoma cells. While executing a non-apoptotic mechanism, we believe the antitumor potential of FA opens up new horizons for the therapy of colorectal malignancy.
天然产物，特别是药用植物，是抗肿瘤药物的重要灵感来源，因为它们含有数量惊人的具有多样化化学结构的小分子。例如，唇形科（以前称为唇形科）的筋骨草属已被报道为天然二萜的丰富来源。在本研究中，我们通过细胞活力测定、流式细胞术评估、定量聚合酶链反应阵列、Western blotting 分析和染色实验，评估了具有 -kaurane 结构的二萜 flexicaulin A（FA）在人类癌细胞中的体外抗增殖特性。随后，我们在结直肠癌的异种移植小鼠模型中验证了 FA 的体内抗肿瘤功效。根据我们的实验结果，FA 似乎是一种有效的抗肿瘤分子，因为它显著抑制了人结直肠癌细胞的体外增殖，并限制了相应异种移植肿瘤的生长，而没有引起任何不良反应。关于其分子机制，FA 显著提高了 p21 的表达水平，并诱导人结直肠癌细胞的细胞周期停滞。虽然执行非凋亡机制，但我们认为 FA 的抗肿瘤潜力为结直肠恶性肿瘤的治疗开辟了新的前景。
