Scaphium affine Ethanol Extract Induces Anoikis by Regulating the EGFR/Akt Pathway in HCT116 Colorectal Cancer Cells

Abstract

Scaphium affine ethanol extracts (SAE) is a species that has been shown to contain various physiological effects; however, its anticancer effects have yet to be revealed. We qualitatively evaluated β-sitosterol in SAE through high-performance liquid chromatography (HPLC). The cytotoxicity in HCT116 and HT29 colorectal cancer cells and CCD841 normal colon cells was confirmed through WST-1 assays. Selective cytotoxicity was observed in colorectal cancer cells, with greater cytotoxicity demonstrated in the HCT116 cell line. As such, the HCT116 colorectal cell line was selected for subsequent experiments. After HCT116 cells were treated with SAE, it was confirmed that the apoptosis rate was increased in a SAE dose-dependent manner through Annexin V assay. SAE further showed dose-dependent suppression of invasion through invasion assays. Anoikis induction through the EGFR/Akt pathway in HCT116 colorectal cancer cells was confirmed by Western blotting. The tumor suppressive effects of SAE was assessed in vivo using a xenograft model of human HCT116 colorectal cancer cells. As a result, we confirmed that SAE decreased tumor size in a dose-dependent manner and that p-EGFR and cleaved-caspase 3 in tumors were also regulated in a dose-dependent manner. This study showed that SAE, by containing β-sitosterol with proven anticancer effects, induces anoikis through the EGFR/Akt pathway in HCT116 colorectal cancer cells both in vitro and in vivo.

The p53-Driven Anticancer Effect of Ribes fasciculatum Extract on AGS Gastric Cancer Cells

“…Although p53 is not involved in direct inhibition of EGFR, it is known to increase sensitivity to EGFR-Tyrosin kinase inhibition. Therefore, the activity of p53 enhances the inhibition of EGFR activity by RFE, and thereby EGFR and Src activity are regulated [57][58][59]. Since increasing the sensitivity to inhibition of EGFR is one of the methods to reduce resistance to EGFR-targeted anticancer drugs, RFE has shown the potential to help overcome anticancer drug resistance.…”

β-Sitosterol as a Promising Anticancer Agent for Chemoprevention and Chemotherapy: Mechanisms of Action and Future Prospects

“…A plethora of scientific studies are available pointing to the role of SIT in activating the intrinsic apoptosis pathway in a variety of cancers, such as liver cancer [ [31] , [32] , [33] , [34] ], cervical cancer [ 35 , 36 ], colon cancer [ [37] , [38] , [39] , [40] , [41] ], stomach cancer [ 42 , 43 ], breast cancer [ 44 , 45 ], leukemia [ 46 , 47 ], multiple myeloma [ 48 ], lung cancer [ 49 , 50 ], melanoma [ 51 ], fibrosarcoma [ 52 ], pancreatic cancer [ 53 ], and prostate cancer [ 54 ] ( Table 1 ). In these cultured cancer cell lines, SIT treatment causes posttranslational activation of caspases, release of cytochrome c, and proteolytic cleavage of PARP and genomic DNA.…”

“…It represents a particular mode of apoptosis, namely a wide range of cellular responses to loss of adhesion that use diverse signaling and apoptotic pathways [ 77 ]. SIT, which has been shown to have anticancer effects in colorectal cancer, induced anoikis by inhibiting the EGFR/AKT signaling pathway [ 40 ]. This provides a basis for the potential use of SIT as an alternative anticancer agent for anoikis resistance–related invasion and metastasis of colorectal cancer.…”

Research progress of ginseng in the treatment of gastrointestinal cancers

“…In human colon cancer cells HT116, β-sitosterol reduced the expression of Bcl-2 and inhibited the apoptosis of protein-1 (cIAP1) while inducing the activation of BAX and cytochrome C. It also reduced tumor size in a dose-dependent manner and induced apoptosis in HCT116 colorectal cancer cells both in vitro and in vivo through the EGFR/Akt pathway ( Kawk et al, 2021 ). β-sitosterol also induces apoptosis through a cystathionine-dependent pathway ( Raj et al, 2022 ).…”