Qi Wang1, Sheng Zhong1, Hua Wu1, Qingquan Wu2. 1. Department of Thoracic Surgery, The Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University, No. 1 Huanghe West Road, Huan'an, 223000, China. 2. Department of Thoracic Surgery, The Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University, No. 1 Huanghe West Road, Huan'an, 223000, China. wuqingquan8888@163.com.
Abstract
BACKGROUND: Marmesin, an important coumarin isolated from Broussonetia kazinoki, has been proposed to possess many pharmacological activities including anti-tumor activity. However, the anti-cancer effect of marmesin on esophageal cancer (EC) has not been characterized. The study aimed to explore the anti-cancer role of marmesin using EC cell lines in vitro. METHODS AND RESULTS: Cell proliferation was evaluated by CCK-8 and Edu cell proliferation assays and apoptosis was detected by TUNEL assay. Western blot analysis was used to determine the expression of Ki67, proliferating cell nuclear antigen (PCNA), Bcl-2, Bax, phosphatidylinositol 3-kinase (PI3K), phosphoryrated-PI3K (p-PI3K), protein kinase B (Akt), and phosphoryrated-Akt (p-Akt). The mechanism of action of marmesin was analyzed using network pharmacology approach. Marmesin exhibited anti-proliferative effect against EC cells, which was further confirmed by the reduced expression of Ki67 and PCNA. Marmesin exerted pro-apoptotic activity on EC cells by downregulating Bcl-2 and upregulating Bax. According to the results from network pharmacology approach, we speculated that PI3K/Akt pathway may participate in the effect of marmesin on EC cells. Additionally, the PI3K/Akt pathway was suppressed by marmesin in EC cells. Moreover, forced expression of Akt reversed the inhibition of cell proliferation and induction of apoptosis induced by marmesin in EC cells. CONCLUSIONS: Marmesin exerted anti-cancer activity in EC cells by inhibiting the PI3K/Akt pathway.
BACKGROUND: Marmesin, an important coumarin isolated from Broussonetia kazinoki, has been proposed to possess many pharmacological activities including anti-tumor activity. However, the anti-cancer effect of marmesin on esophageal cancer (EC) has not been characterized. The study aimed to explore the anti-cancer role of marmesin using EC cell lines in vitro. METHODS AND RESULTS: Cell proliferation was evaluated by CCK-8 and Edu cell proliferation assays and apoptosis was detected by TUNEL assay. Western blot analysis was used to determine the expression of Ki67, proliferating cell nuclear antigen (PCNA), Bcl-2, Bax, phosphatidylinositol 3-kinase (PI3K), phosphoryrated-PI3K (p-PI3K), protein kinase B (Akt), and phosphoryrated-Akt (p-Akt). The mechanism of action of marmesin was analyzed using network pharmacology approach. Marmesin exhibited anti-proliferative effect against EC cells, which was further confirmed by the reduced expression of Ki67 and PCNA. Marmesin exerted pro-apoptotic activity on EC cells by downregulating Bcl-2 and upregulating Bax. According to the results from network pharmacology approach, we speculated that PI3K/Akt pathway may participate in the effect of marmesin on EC cells. Additionally, the PI3K/Akt pathway was suppressed by marmesin in EC cells. Moreover, forced expression of Akt reversed the inhibition of cell proliferation and induction of apoptosis induced by marmesin in EC cells. CONCLUSIONS: Marmesin exerted anti-cancer activity in EC cells by inhibiting the PI3K/Akt pathway.