Cucurbitacin B Inhibits the Hippo-YAP Signaling Pathway and Exerts Anticancer Activity in Colorectal Cancer Cells

Chai, Yanting; Xiang, Ke; Wu, Yezi; Zhang, Te; Liu, Ying; Li, Xuewen; Zhen, Weiguo; Su, Yuan

doi:10.12659/msm.911594

Cited by 33 publications

(19 citation statements)

References 31 publications

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“…These compounds have a broad spectrum of pharmacological activities including antioxidant, anticancer, and antidiabetic. Chai et al reported Cucurbitacin B exerts anticancer activities in colorectal cancer cells by inhibiting YAP protein [146].…”

Section: Function Of Hippo Pathway In Cancersmentioning

confidence: 99%

Analysis of the role of the Hippo pathway in cancer

2019

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Cancer is a serious health issue in the world due to a large body of cancer-related human deaths, and there is no current treatment available to efficiently treat the disease as the tumor is often diagnosed at a serious stage. Moreover, Cancer cells are often resistant to chemotherapy, radiotherapy, and molecular-targeted therapy. Upon further knowledge of mechanisms of tumorigenesis, aggressiveness, metastasis, and resistance to treatments, it is necessary to detect the disease at an earlier stage and for a better response to therapy. The hippo pathway possesses the unique capacity to lead to tumorigenesis. Mutations and altered expression of its core components (MST1/2, LATS1/2, YAP and TAZ) promote the migration, invasion, malignancy of cancer cells. The biological significance and deregulation of it have received a large body of interests in the past few years. Further understanding of hippo pathway will be responsible for cancer treatment. In this review, we try to discover the function of hippo pathway in different diversity of cancers, and discuss how Hippo pathway contributes to other cellular signaling pathways. Also, we try to describe how microRNAs, circRNAs, and ZNFs regulate hippo pathway in the process of cancer. It is necessary to find new therapy strategies for cancer.

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Section: Function Of Hippo Pathway In Cancersmentioning

confidence: 99%

Analysis of the role of the Hippo pathway in cancer

2019

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“…Two studies demonstrated that CuE inhibits the EGFR/MAPK/ERK signaling pathway in cancer cells (33,34). Recently, CuB was shown to inhibit the Hippo/YAP pathway in human colorectal cancer cell lines (35). These findings lead us to believe that CuE inhibits YAP indirectly through the EGFR/MAPK/ERK and Hippo/YAP signaling pathways in human NSCLC.…”

Section: Discussionmentioning

confidence: 98%

“…Our study is the first to show that CuE suppresses brain metastasis of human NSCLC in a murine model. A recent study showed that cucurbitacin B (another tetracyclic cucurbitane) inhibits the Hippo-YAP signaling pathway in colorectal cancer cells, but included no in vivo data (35). Another study demonstrated that CuE inhibited breast cancer in a mouse model of metastasis by suppressing cell migration and invasion, but the anti-cancer mechanism of CuE was not investigated (18).…”

Section: Discussionmentioning

confidence: 99%

Cucurbitacin E inhibits the Yes‑associated protein signaling pathway and suppresses brain metastasis of human non‑small cell lung cancer in a murine model

et al. 2019

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Human non-small cell lung cancer (NSCLC) is associated with an extremely poor prognosis especially for the 40% of patients who develop brain metastasis, and few treatment strategies exist. Cucurbitacin E (CuE), an oxygenated tetracyclic triterpenoid isolated from plants particularly of the family Cucurbitaceae, has shown anti-tumorigenic properties in several types of cancer, yet the mechanism remains unclear. Yes-associated protein (YAP), a main mediator of the Hippo signaling pathway, promotes tumorigenesis, drug resistance and metastasis in human NSCLC. The present study was designed to ascertain whether CuE inhibits YAP and its downstream gene expression in the human NSCLC cell lines H2030-BrM3 (K-ras G12C mutation) and PC9-BrM3 (EGFR Δexon19 mutation), which have high potential for brain metastasis. The efficacy of CuE in suppressing brain metastasis of H2030-BrM3 cells in a murine model was also investigated. It was found that after CuE treatment in H2030-BrM3 and PC9-BrM3 cells, YAP protein expression was decreased, and YAP signaling GTIIC reporter activity and expression of the downstream genes CTGF and CYR61 were significantly (P<0.01) decreased. CuE treatment also reduced the migration and invasion abilities of the H2030-BrM3 and PC9-BrM3 cells. Finally, our in vivo study showed that CuE treatment (0.2 mg/kg) suppressed H2030-BrM3 cell brain metastasis and that mice treated with CuE survived longer than the control mice treated with 10% DMSO (P=0.02). The present study is the first to demonstrate that CuE treatment inhibits YAP and the signaling downstream gene expression in human NSCLC in vitro, and suppresses brain metastasis of NSCLC in a murine model. More studies to verify the promising efficacy of CuE in inhibiting brain metastasis of NSCLC and various other cancers may be warranted.

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“…27,28 Among various signaling pathways, the Hippo-YAP signaling pathway has been identified to be involved in the regulation of multiple tumors. 29,30 These analyses indicated that the interaction between LATS2 and the Hippo-YAP signaling pathway might underlie the regulatory function of miR-224-3p in the progression of retinoblastoma. Accumulating evidence has suggested that activation of the Hippo-YAP signaling pathway plays an antitumor role in different types of cancer, including gastric cancer, breast cancer, and prostate cancer.…”

Section: Yap/taz Figurementioning

confidence: 97%