Purpurin binding interacts with LHPP protein that inhibits PI3K/AKT phosphorylation and induces apoptosis in colon cancer cells HCT‐116

Abstract

Colorectal cancer (CRC) is the leading type of diagnosed cancer; globally, it resides in the fourth‐leading origin of cancer‐interrelated mortality in the globe. The treatment strategies were chemotherapy and potent radiotherapy. Although chemotherapy treatment can eliminate tumor cells, it remains with unnecessary toxic effects in cancer patients. Therefore, the identification of natural‐based compounds, which have selectively inhibiting target proteins with limited toxicity that can facilitate the therapeutic approaches against CRC. In this existing approach, which highlights the binding efficacy of our anthraquinone compound, purpurin against phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) protein restrains the CRC cell growth by inhibiting phosphatidylinositol‐3‐kinase/protein kinase B (PI3K/AKT), cell proliferation, and inducing apoptosis signaling. Primarily, purpurin (36 μM) exposed to HCT‐116 cells and incubated for 24 and 48 h could induce reactive oxygen species production, subsequently alter mitochondrion membrane, and increase the apoptotic cells in HCT‐116. LHPP, a kind of histidine phosphatase protein, has been considered as a tumor suppressor in numerous carcinomas. However, purpurin‐mediated LHPP proteins and its associated molecular events in CRC remain unclear. In our docking studies revealed that purpurin has been strongly interacts with LHPP via hydrophobic and hydrophilic binding interaction. Western blot results confirmed that purpurin enhances the expression of LHPP protein, thereby inhibits the expression of phosphorylated‐PI3K/AKT, EGFR, cyclin‐D1, PCNA in HCT‐116 cells. Moreover, purpurin induces messenger RNA expression of apoptotic genes (Bax, CASP‐9, and CASP‐3) in HCT‐116 cells. Thus, we conclude that purpurin could be a natural and useful compound, which inhibits the growth of CRC cells through the activation of LHPP proteins.

Exploring the Mechanism of Action of Canmei Formula Against Colorectal Adenoma Through Multi-Omics Technique

“…The phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) signaling pathway is one of the most classical pathways involved in tumorigenesis ( Xie et al, 2019 ). Previous results indicated that cell cycle was arrested in the G0/G1 phase after improved expression of Lhpp, while reduction of Lhpp displayed the opposite results ( Li Z. et al, 2021 ). Therefore, the role of Lhpp is similar to that of tumor suppressor gene, indicating that CMF may inhibit the occurrence of CRA by regulating the expression of Lhpp.…”

Long noncoding RNA DLGAP1-AS2 promotes tumorigenesis and metastasis by regulating the Trim21/ELOA/LHPP axis in colorectal cancer

“…We revealed that DLGAP1-AS1 regulated several key cancer-related pathways, including PI3K/AKT. Interestingly, recent studies have reported that LHPP inhibits the PI3K/AKT signaling pathway in CRC [ 17 , 18 ]. We found that LHPP was expressed at lower levels in CRC tissues compared with NCTs based on multiple public CRC cohorts (Fig.S 10 A).…”

The Protective Mechanism of Afuresertib against Esophageal Cancer

“…PI3K can directly cause phosphorylation of the downstream effector molecule Akt. When the PI3K/Akt pathway is activated, the Akt phosphorylation level increases, and when the PI3K/Akt pathway is inhibited, the Akt phosphorylation level decreases [ 30 – 32 ]. In this study, compared with the model group, the expression levels of PI3K, p-PI3K, Akt, and p-Akt proteins in the tumor tissues of the rats in each group were decreased in a dose-dependent manner after afuresertib intervention.…”