Shikonin inhibits the proliferation of cervical cancer cells via FAK/AKT/GSK3β signalling

Abstract

Cervical cancer is one of the most lethal malignancies of the female reproductive system. Shikonin, a naphthoquinone pigment extracted from the traditional medicinal herb, Lithospermum erythrorhizon, has been demonstrated to exert significant inhibitory effects on a variety of tumours in vitro and in vivo. In the present study, the effects of shikonin on cervical cancer and the underlying mechanisms were investigated. The effects of shikonin on the viability on HeLa and SiHa cervical cancer cells was examined using cell counting kit (CCK-8) and colony formation assays. Immunofluorescence assay was performed to detect the levels of the proliferation-related protein, Ki67. Western blot analysis was utilized to measure the phosphorylated and total expression levels of proteins, including focal adhesion kinase (FAK), AKT, and glycogen synthase kinase 3β (GSK3β). Cell migration was determined by using wound healing assay. Metastasis-associated 1 (MTA1), TGFβ1 and VEGF mRNA expression levels were determined using reverse transcription-quantitative PCR. It was demonstrated that, shikonin inhibited cervical cancer cell proliferation and migration. The data of the present study revealed that shikonin inhibited the proliferation of HeLa and SiHa cells in a concentration-and time-dependent manner. Mechanistically, shikonin blocked the proliferation of cervical cancer cells by downregulating the phosphorylation of FAK, AKT and GSK3β induced by EGF. In addition, shikonin significantly suppressed cell migration and reduced the expression of migration-related proteins, including MTA1, TGFβ1 and VEGF. On the whole, the present study demonstrates that shikonin may exert an inhibitory effect on the cervical cancer cell proliferation and migration through the FAK/AKT/GSK3β signaling pathway. These findings suggest that shikonin may function as a potential therapeutic drug for the treatment of cervical cancer.

USP14 promotes the proliferation of cervical cancer via upregulating β‐catenin

“…Studies have confirmed that many tumors, such as gastric and colorectal cancer, have a high expression of GSK3β 47 . In addition, a large number of studies have shown that in CC, GSK3β is involved in the regulation of the PI3K/Akt signaling pathway and the promotion of the malignant progression of CC cells 48,49 . This suggests that the regulatory role of USP14 in CC progression may be due to interactions with different key signaling pathways.…”

“…47 In addition, a large number of studies have shown that in CC, GSK3β is involved in the regulation of the PI3K/Akt signaling pathway and the promotion of the malignant progression of CC cells. 48,49 This suggests that the regulatory role of USP14 in CC progression may be due to interactions with different key signaling pathways. The pathway of USP14 action in CC may be a type of network rather than a single upstream and downstream pathway.…”

Deoxyshikonin triggers apoptosis in cervical cancer cells through p38 MAPK‐mediated caspase activation

“…Among the phytochemicals, the biological activities of shikonin and its natural derivatives have been widely explored in the past decade. Shikonin exhibits a variety of biological activities through different targets and molecular pathways, including inhibition of Epstein-Barr virus reactivation through NLRP3 downregulation, 29 suppression of cervical cancer cell proliferation through FAK signaling pathway, 30 and induction of necroptosis in NPC cells through ROS and RIPK1/ RIPK3/MLKL upregulation. 31 Recently, functional activities and targets of novel synthetic shikonin derivatives for colorectal cancer treatment are also evaluated.…”

Research progress in mechanism of anticancer action of shikonin targeting reactive oxygen species

“…The therapeutic potential of Shikonin against a range of systemic malignancies has been thoroughly investigated, encompassing lung cancer, lymphoma, leukemia, gastric cancer, colorectal cancer, hepatocellular carcinoma, pancreatic cancer, and breast cancer ( Tang et al, 2018 ; Guo et al, 2019b ; Ji et al, 2022 ; Li et al, 2022 ; Xu et al, 2022 ; Dong et al, 2023 ; Király et al, 2023 ; Qian et al, 2023 ; Zhang et al, 2023 ). Shikonin is rich in various chemical constituents, including naphthoquinones, flavonoids, phenolic acids, terpenes, and polysaccharides.…”