Abstract
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, Isodon (formerly Rabdosia), 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 Isodon diterpenoid with an ent-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.
Highlights
Abnormal cell growth gives rise to the formation of tumors, which become either benign or malignant
The human colorectal carcinoma HT-29 cells were less sensitive to flexicaulin A (FA) when compared to the HCT-116 cells; we suggest that p53 may play a role in the molecular action of FA
The ent-kaurane diterpenoid FA was purchased from Gihon Biotech, Hong Kong, and dissolved in dimethylsulfoxide (DMSO) to a stock solution at 1 mM, which was kept at –20 ◦C until use
Summary
Abnormal cell growth gives rise to the formation of tumors, which become either benign or malignant. Malignant tumors, commonly known as cancers, can cause serious illness and death. Tumor cells are defined as highly proliferative because they continue to divide, evading the normal growth inhibitory controls. Apoptosis is one of the major mechanisms that restricts cellular proliferation in response to DNA damage, oncogenic stimuli, and physiological stresses [2,3]. It is not surprising that the vast majority of anticancer drugs currently used in clinical oncology are apoptotic inducers. The rate of cellular proliferation is governed by the cell cycle process and rhythm.
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