Induction of G0/G1 Phase Cell Cycle Arrest and Apoptosis by <i>Aegiceras corniculatum</i> in Human Colorectal Cancer via Activation of FoxO Signalling

Abstract

Background: Aegiceras corniculatum (Linn.) Blanco, commonly known as black mangrove, river mangrove, kacang-kacang, and Narikandam, is a mangrove plant, found from India through Southeast Asia to southern China and Australia. Aegiceras corniculatum is known to exhibit anticancer effects against different types of cancer; however, the anticancer activity and underlying mechanisms of action of A. corniculatum leaf extract on colorectal cancer (CRC) have not been elucidated. Methods: In the present study, a colony-forming assay, western blot, flow cytometry and a xenografts model were applied to investigate the effects of n-butanol extract of A. corniculatum leaves (NACL) on CRC in vitro and in vivo. Findings: The results showed that NACL inhibits the viability and proliferation of CRC cells in a dose-dependent manner. Besides, NACL also induces cell apoptosis and cell cycle arrest by activating Forkhead box proteins and controlling the cell cycle checkpoint pathways, which are associated with the caspase-dependent mitochondrial apoptotic cascades and Bcl-2 family proteins. More importantly, the tumour sizes in HT-29 xenograft nude mice decreased after treatment with NACL in vivo. Significance: These findings demonstrate that A. corniculatum leaf extracts have potent anti-cancer activities across different colorectal and other solid tumor cell lines, via regulating cell cycle and apoptosis pathway, thus it has the potential to be developed as an anticancer therapy to enhance other standard of cares in the clinic for patients with CRC. Funding Statement: The work was supported by Guangxi scientific research and technology development plan project (No. GKH15104001-11), Guangxi Science and Technology Plan Projects (No. GKAD17195025), and Guangxi Key Laboratory Construction Project (No.17-259-20). Declaration of Interests: All authors state there are no conflicts of interest to disclose. Ethics Approval Statement: Experimental conditions and procedures involving animals were approved by the Institutional Animal Ethics Committee (IAEC) of Guangxi Medical University (Nanning, Guangxi, China). The experiments were carried out in accordance with the Laboratory Animal Use Guidelines of IAEC. Animal handling followed the National Animal Welfare Law of China.