Role of Episamarcandin in Promoting the Apoptosis of Human Colon Cancer HCT116 Cells through the PI3K-Akt Signaling Pathway

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.

The potential mechanism of Bletilla striata in the treatment of ulcerative colitis determined through network pharmacology, molecular docking, and in vivo experimental verification

“…EGFR signalling is also an important marker of colitis-related colorectal carcinogenesis (Ko et al 2019 ; Singh et al 2018 ). PI3K/AKT is a key downstream signalling pathway of EGFR, and abnormal activation of the PI3K/AKT signalling pathway is associated with the development of UC, as well as promoting colon cancer cell proliferation, prolonging cell survival, inhibiting cell apoptosis, and participating in angiogenesis, leading to invasion and metastasis of colon cancer (Jiang et al 2019a , b ; Zhang et al 2021 ). In addition, the PI3K-AKT pathway is closely related to the regulation of the inflammatory response during UC progression.…”

Changing the Landscape of Solid Tumor Therapy from Apoptosis-Promoting to Apoptosis-Inhibiting Strategies

“…Such a discrepancy in IC50 values for inhibition of cell proliferation and induction of apoptosis has been observed for various solid tumor-derived cell lines after exposure to cisplatin or other chemotherapeutic drugs (e.g., oxaliplatin, paclitaxel, and doxorubicin) (for details, see [108][109][110]). apoptosis [111], and ~100 µM cisplatin induced ~30% [112] and ~60% [113] apoptosis in this cell line.…”

“…Since then, other groups have used different assays and confirmed that very high concentrations of cisplatin are required to engage apoptosis in a significant proportion of cells within HCT116 cultures. For example, 60 µM cisplatin induced ~20% apoptosis [ 111 ], and ~100 µM cisplatin induced ~30% [ 112 ] and ~60% [ 113 ] apoptosis in this cell line. In our own work [ 110 ], we observed higher levels of apoptosis compared to other groups, but, consistent with other groups, we also observed marginal levels of apoptosis at the MTD (~10 µM).…”

Changing the Landscape of Solid Tumor Therapy From Apoptosis-Promoting to Apoptosis-Inhibiting Strategies

“…Since then, other groups have used different assays and confirmed that very high concentrations of cisplatin is required to engage apoptosis in a significant proportion of cells within HCT116 cultures. For example, 60 µM cisplatin induced ~20% apoptosis [111], and ~100 µM cisplatin induced ~30% [112] and ~60% [113] apoptosis in this cell line.…”

“…Since then, other groups have used different assays and confirmed that very high concentrations of cisplatin is required to engage apoptosis in a significant proportion of cells within HCT116 cultures. For example, 60 µM cisplatin induced ~20% apoptosis[111], and ~100 µM cisplatin induced ~30%[112] and ~60%[113] apoptosis in this cell line. In our own work[110], we observed higher levels of apoptosis compared to other groups but, consistent with other groups, we also observed marginal levels of apoptosis at the MTD (~10 µM).…”