Abstract
This study identifies the active ingredients of Ferula sinkiangensis and investigates the role and mechanism of episamarcandin in colon cancer cells. The silica gel column chromatography was utilized to separate the chemical components of Ferula sinkiangensis. Sephadex LH-20 and semipreparative HPLC were adopted for further separation and purification. The compound episamarcandin showed good anticolon cancer activity among the 13 monomeric compounds obtained. Its effects on the apoptosis, cell cycle, and invasion and migration of colon cancer HCT 116 cells and PI3K-Akt signaling pathway were further investigated. The results showed that, similar to positive control cisplatin, episamarcandin inhibited the proliferation, promoted the apoptosis, arrested cells at G0/G1 phase, and suppressed migration and invasion of HCT 116 cells. A large number of apoptotic HCT 116 cells were observed under a transmission electron microscope. Fluorescence real-time quantitative PCR and western blot analysis showed that episamarcandin increased the expression of PTEN, p53, and Bax and decreased the expression of P-Akt, Akt, mTOR, Bcl-xl, and Bcl-2. Conclusively, episamarcandin may inhibit cell proliferation, migration, and invasion and promote the apoptosis of human colon cancer HCT 116 cells possibly through the PI3K-Akt signaling pathway.
Highlights
Ferula belongs to Peucedaneae of Apiaceae, mainly distributed in Central Asia, such as Iran, Pakistan, Turkey, and the former Soviet Union. ere are 31 species in China [1]. e Chinese Pharmacopoeia (2015 edition) includes the resin of Ferula sinkiangensis or Ferula fukanensis [2]
Studies have reported that plants of Ferula can inhibit proliferation and induce apoptosis and cell cycle arrest in human colon cancer HCT 116 cells, human glioma U87 cells, Raji lymphoma cells, cervical adenocarcinoma HeLa cells, and breast cancer MCF-7 cells as well as reducing the metastasis of breast cancer to lungs, livers and kidneys in animal models [4,5,6]
MTT and SRB methods were used to verify the inhibitory effect of the 13 obtained monomer compounds on the proliferation of human colon cancer HCT 116 cells, which showed that the sesquiterpene coumarin compound episamarcandin had a significant inhibitory effect on HCT 116 cells. en, we evaluated the role and mechanism of episamarcandin in colon cancer cells
Summary
Ferula (about 150 species) belongs to Peucedaneae of Apiaceae, mainly distributed in Central Asia, such as Iran, Pakistan, Turkey, and the former Soviet Union. ere are 31 species in China [1]. e Chinese Pharmacopoeia (2015 edition) includes the resin of Ferula sinkiangensis or Ferula fukanensis [2]. Ferula (about 150 species) belongs to Peucedaneae of Apiaceae, mainly distributed in Central Asia, such as Iran, Pakistan, Turkey, and the former Soviet Union. Ferula sinkiangensis is mainly distributed in Yining County of Xinjiang and is endemic to China. Studies have reported that plants of Ferula can inhibit proliferation and induce apoptosis and cell cycle arrest in human colon cancer HCT 116 cells, human glioma U87 cells, Raji lymphoma cells, cervical adenocarcinoma HeLa cells, and breast cancer MCF-7 cells as well as reducing the metastasis of breast cancer to lungs, livers and kidneys in animal models [4,5,6]. Our research group has reported the antitumor and antioxidant activities of Ferula sinkiangensis [7,8,9,10]. The specific antitumor active ingredients and mechanism of action remain unclear
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