Cucurbitacins: elucidation of their interactions with the cytoskeleton

Wang, Xiaojuan; Tanaka, Mine; Peixoto, Herbenya

doi:10.7717/peerj.3357

Cited by 26 publications

(34 citation statements)

References 44 publications

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“…In recent years, many studies have reported that CuB can inhibit cell proliferation and induce apoptosis of different types of cancer cells, and it has become a potentially safe anticancer drug (Chen et al, 2012;Promkan, Dakeng, Chakrabarty, Bogler, & Patmasiriwat, 2013;Shukla et al, 2015;Zhang, Gao, & Yang, 2017). Previous studies have shown that CuB interacts with the cytoskeleton by affecting actin filaments and the microtubule, and the cytoskeleton appears to be an early target (Wang, Tanaka, Peixoto, & Wink, 2017;Zhang et al, 2014). However, the effect of CuB on the mechanical properties of breast cancer cells, which could influence the migration and invasion, has very rarely been reported.…”

mentioning

confidence: 99%

Cucurbitacin B inhibits the migration and invasion of breast cancer cells by altering the biomechanical properties of cells

Liang

Zhang

Yuan

et al. 2018

Phytotherapy Research

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Changes in cellular biomechanical properties affect cell migration and invasion. The natural compound Cucurbitacin B (CuB) has potent anticancer activity; however, the mechanism underlying its inhibitory effect on breast cancer metastasis needs further study. Here, we showed that low‐dose CuB inhibited adhesion and altered the viscoelasticity of breast cancer cells, thereby, reducing cell deformability. In vitro and in vivo experiments proved that CuB effectively inhibited the migration and invasion of breast cancer cells. Further studies have found that CuB downregulated the expression of F‐actin/vimentin/FAK/vinculin in breast cancer cells, altering the distribution and reorganization of cytoskeletal proteins in the cells. CuB inhibited signaling by the Rho family GTPases RAC1/CDC42/RhoA downstream of integrin. These findings indicate that CuB has been proven to mediate the reorganization and distribution of cytoskeletal proteins of breast cancer cells through RAC1/CDC42/RhoA signaling, which improves the mechanical properties of cell adhesion and deformation and consequently inhibits cell migration and invasion.

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mentioning

confidence: 99%

Cucurbitacin B inhibits the migration and invasion of breast cancer cells by altering the biomechanical properties of cells

Liang

Zhang

Yuan

et al. 2018

Phytotherapy Research

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“…The cytotoxic effect of CuB was tested on HeLa and U2OS cells, and the IC 50 values were 12.2 and 17.07 μM, respectively. The inhibition of tubulin polymerization in vitro was observed with an IC 50 > 1 mM [13]. CuB from the leaves of Tunisian E. elaterium exhibited an anticancer effect and displayed anti-integrin activity in human glioblastoma U87 cells, with no cytotoxicity observed at concentrations up to 500 nM.…”

Section: Cucurbitacin B (1′)mentioning

confidence: 93%

“…The cytotoxic effect of CuE was tested on HeLa and U2OS cells, and the IC 50 values were 6.43 and 15.07 nM, respectively. The inhibition of tubulin polymerization in vitro had an IC 50 of 566.91 nM [13].…”

Section: Cucurbitacin E (4′)mentioning

confidence: 99%

“…The cytotoxicity of CuI was tested in HeLa and U2OS cells, and the IC 50 values were 44.77 and 23.47 nM, respectively. The inhibition of tubulin polymerization in vitro had an IC 50 > 1 mM [13]. The effects of CuI purified from E. elaterium fruit on the expression of the BAX, caspase-3, LC3, and VEGF and c-MYC genes in the AGS cell line were investigated.…”

Section: Cucurbitacin I (6′)mentioning

confidence: 99%

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Cytotoxic and Antitumoral Activities of Compounds Isolated from Cucurbitaceae Plants

Méndez-Cuesta¹,

Campos²,

Sánchez³

et al. 2019

Pharmacognosy - Medicinal Plants

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The WHO says that annual cases of cancer will increase from 14 million in 2012 to 22 million in the next two decades. Cancer is the second cause of death in the world; in 2015, it caused 8.8 million deaths. On the other hand, it is necessary to consider that 70% of the total deaths due to this disease occur in developing countries, who have the least resources to acquire the drugs of choice for the treatment of this disease. Although there are treatments and these are effective, there are currently cases of resistance to drugs used to treat this disease, which has led to the search for new sources of drugs or compounds effective against the cancer being active; plants are the possible sources to achieve this. Cucurbitaceae is a family of plants widely distributed on the planet which has been used traditionally for the treatment of this disease and from they have been isolated different cucurbitanes. These compounds possess a wide biological activity, antidiabetic, anti-inflammatory, hepatoprotective, or cytotoxic and antitumoral effects. The aim of this review is to present 51 cucurbitacin compounds and 2 with different structures isolated from Cucurbitaceae plants with cytotoxic or antitumoral activity.

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“…Previous studies indicated that CuE could significantly inhibit the growth of breast cancer cells and HL-60 cells by inducing G2/M cell cycle arrest 14,22,23. Moreover, CuE could induce cell cycle arrest at the G2/M phase by altering mitotic spindles in U2OS, MCF7 and HeLa cancer cells 24. According to the current study, accumulation of CuE in GBM8401 and U-87-MG cells is the major cause leading to both the inhibition of cell proliferation and G2/M phase arrest.…”

mentioning

confidence: 97%

The effects of cucurbitacin E on GADD45β‐trigger G2/M arrest and JNK‐independent pathway in brain cancer cells

Cheng

Hsu

Tsai

2019

J Cellular Molecular Medi

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Cucurbitacin E (CuE), an active compound of the cucurbitacin family, possesses a variety of pharmacological functions and chemotherapy potential. Cucurbitacin E exhibits inhibitory effects in several types of cancer; however, its anticancer effects on brain cancer remain obscure and require further interpretation. In this study, efforts were initiated to inspect whether CuE can contribute to anti‐proliferation in human brain malignant glioma GBM 8401 cells and glioblastoma‐astrocytoma U‐87‐MG cells. An MTT assay measured CuE's inhibitory effect on the growth of glioblastomas (GBMs). A flow cytometry approach was used for the assessment of DNA content and cell cycle analysis. DNA damage 45β (GADD45β) gene expression and CDC2/cyclin‐B1 disassociation were investigated by quantitative real‐time PCR and Western blot analysis. Based on our results, CuE showed growth‐inhibiting effects on GBM 8401 and U‐87‐MG cells. Moreover, GADD45β caused the accumulation of CuE‐treated G2/M‐phase cells. The disassociation of the CDC2/cyclin‐B1 complex demonstrated the known effects of CuE against GBM 8401 and U‐87‐MG cancer cells. Additionally, CuE may also exert antitumour activities in established brain cancer cells. In conclusion, CuE inhibited cell proliferation and induced mitosis delay in cancer cells, suggesting its potential applicability as an antitumour agent.

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Cucurbitacins: elucidation of their interactions with the cytoskeleton

Cited by 26 publications

References 44 publications

Cucurbitacin B inhibits the migration and invasion of breast cancer cells by altering the biomechanical properties of cells

Cucurbitacin B inhibits the migration and invasion of breast cancer cells by altering the biomechanical properties of cells

Cytotoxic and Antitumoral Activities of Compounds Isolated from Cucurbitaceae Plants

The effects of cucurbitacin E on GADD45β‐trigger G2/M arrest and JNK‐independent pathway in brain cancer cells

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