In vitro antitumor effect of cucurbitacin E on human lung cancer cell line and its molecular mechanism

Jing, Siyuan; Wu, Zhimin; Zhang, Tiehua; Zhang, Jie; Wei, Zhengyi

doi:10.1016/s1875-5364(20)30058-3

Cited by 11 publications

(6 citation statements)

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“…The name and accordingly the activity of cucurbitacins vary depending on the position of the double bonds, ketone groups, and hydroxyl groups in the main skeleton of the compound (Chen et al, 2005). As cucurbitacins have a wide variety of biological activities, cucurbitacin derivatives have been demonstrated to have mainly antitumor (Jing et al, 2020;Wang et al, 2021), antiproliferative (Marostica et al, 2015), analgesic (Oridupa et al, 2013), antipyretic (Agil et al, 1995), anti-inflammatory (Peng et al, 2020) For this purpose, the present study attempted to report the effect of CuI on HepG2 cell viability using Sorafenib, which is used for the treatment of HCC, as a positive control (Figure 2). The IC 50 value obtained after 48 h of administration of Sorafenib to HepG2 cells was 1.08 μM.…”

Section: Discussionmentioning

confidence: 99%

“…The name and accordingly the activity of cucurbitacins vary depending on the position of the double bonds, ketone groups, and hydroxyl groups in the main skeleton of the compound (Chen et al, 2005). As cucurbitacins have a wide variety of biological activities, cucurbitacin derivatives have been demonstrated to have mainly antitumor (Jing et al, 2020; Wang et al, 2021), antiproliferative (Marostica et al, 2015), analgesic (Oridupa et al, 2013), antipyretic (Agil et al, 1995), anti‐inflammatory (Peng et al, 2020), and hepatoprotective (El Naggar et al, 2015) effects. The present study is the first to show that CuI extracted from the E. elaterium plant inhibits hepatocellular carcinoma cell proliferation by affecting cancer‐associated JAK/STAT3 pathway, PI3K/Akt/mTOR signaling, and p38/ERK/JNK pathways.…”

Section: Discussionmentioning

confidence: 99%

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Cucurbitacin I exhibits anticancer efficacy through induction of apoptosis and modulation of JAK / STAT3 , MAPK / ERK , and AKT / mTOR signaling pathways in HepG2 cell line

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et al. 2022

Journal of Food Biochemistry

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Hepatocellular carcinoma is a common cancer type, especially among men. Although cucurbitacin I (CuI), widely found in plants belonging to the Ecballium elaterium (E. L) plant family, has been shown to have antitumorigenic properties in many cancer types, its anticancer effect, molecular mechanism, and apoptotic effect mediated by signal pathways on hepatocellular carcinoma have not been fully clarified. In the present study, we investigated the anticancer effect of CuI treated at different doses on the HepG2 cell line and the underlying mechanism in vitro. High-purity CuI was obtained from the E. elaterium plant with the aid of HPLC. The effects of this substance on the viability of cells were studied by the MTT assay. The effects of CuI on cell cycle progression and apoptosis were studied with flow cytometry. DNA breaks were analyzed by the Comet assay method.The proteins and genes involved in the JAK/STAT3, MAPK/ERK, and AKT/mTOR signaling pathways were investigated using Western blot and qRT-PCR, respectively. The results of this study demonstrated that CuI significantly reduced HepG2 cell growth in vitro, induced antiproliferation, and G2/M phase of the cell cycle was interrupted. Practical applicationsCuI administration was shown to downregulate the levels of proteins in the PI3K/ AKT/mTOR, MAPK, and JAK2/STAT3 cascades in HepG2 cells. CuI also reduced the expression of MAPK, STAT3, mTOR, JAK2, and Akt genes in different concentrations.DNA breaks are formed as a result of this effect. CuI, by reducing cell proliferation and promoting apoptosis, was found to have potential as a chemotherapeutic agent of hepatocellular carcinoma.

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Section: Discussionmentioning

confidence: 99%

“…The name and accordingly the activity of cucurbitacins vary depending on the position of the double bonds, ketone groups, and hydroxyl groups in the main skeleton of the compound (Chen et al, 2005). As cucurbitacins have a wide variety of biological activities, cucurbitacin derivatives have been demonstrated to have mainly antitumor (Jing et al, 2020; Wang et al, 2021), antiproliferative (Marostica et al, 2015), analgesic (Oridupa et al, 2013), antipyretic (Agil et al, 1995), anti‐inflammatory (Peng et al, 2020), and hepatoprotective (El Naggar et al, 2015) effects. The present study is the first to show that CuI extracted from the E. elaterium plant inhibits hepatocellular carcinoma cell proliferation by affecting cancer‐associated JAK/STAT3 pathway, PI3K/Akt/mTOR signaling, and p38/ERK/JNK pathways.…”

Section: Discussionmentioning

confidence: 99%

Cucurbitacin I exhibits anticancer efficacy through induction of apoptosis and modulation of JAK / STAT3 , MAPK / ERK , and AKT / mTOR signaling pathways in HepG2 cell line

Üremiş

Uremis

Çiğremiş

et al. 2022

Journal of Food Biochemistry

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“…Previous reports have also shown that CuE has remarkable potential in suppressing the growth of multiple cancer cell types [ 18 , 30 , 31 ]. CuE can inhibit cell proliferation, induce cell cycle arrest and enhance apoptotic cell death by modulating the STAT3, MAPK, PI3K/AKT, Wnt/beta-catenin and mTOR signalling pathways [ 17 , 19 , 32 – 34 ]. CuE can also suppress angiogenesis by inhibiting the VEGFR2-mediated JAK2 − STAT3 signalling pathway and cancer cell metastasis by inhibiting depolymerization of actin filaments [ 35 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

Cucurbitacin E inhibits cellular proliferation and induces apoptosis in melanoma by suppressing HSDL2 expression

et al. 2022

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Background Melanoma is among the most aggressive types of skin malignancy and can have an unpredictable clinical course. Exploration of novel therapeutic targets and their regulators remains essential for the prevention and treatment of melanoma. Methods HSDL2 protein levels were examined by immunohistochemistry. The roles of HSDL2 in cell proliferation and apoptosis were identified by CCK-8 and colony formation assays. The function of HSDL2 in cell apoptosis was analysed by flow cytometry. Western blotting, cell proliferation and apoptosis and a xenograft tumour model were utilized to explore the inhibitory functions and mechanisms of CuE in melanoma. Results HSDL2 is overexpressed in melanoma and promotes melanoma progression by activating the ERK and AKT pathways. CuE could inhibit the ERK and AKT pathways by decreasing HSDL2 expression; therefore, CuE could inhibit melanoma growth in vitro and in vivo. Conclusion HSDL2 may be a promising therapeutic target against melanoma, and CuE can inhibit melanoma by downregulating HSDL2 expression.

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“…Cucurbitacin E reduced cyclin A2, cyclin B1 and cyclin E1 levels, resulting in an accumulation of cells at the G1/G0 phase of the cell cycle. Finally, the article showed that the derivative increased the phosphorylation of EGFR, altering the phosphorylation levels of the downstream members ERK1/2 and MEK1/2, found upregulated and downregulated, respectively [ 74 ].…”

Section: Cucurbitacins In Anticancer Pharmacological Research: Molecu...mentioning

confidence: 99%

Cucurbitacins as potential anticancer agents: new insights on molecular mechanisms

et al. 2022

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Since ancient times, plants have been an extensive reservoir of bioactive compounds with therapeutic interest for new drug development and clinical application. Cucurbitacins are a compelling example of these drug leads, primarily present in the plant kingdom, especially in the Cucurbitaceae family. However, these natural compounds are also known in several genera within other plant families. Beyond the Cucurbitaceae family, they are also present in other plant families, as well as in some fungi and one shell-less marine mollusc. Despite the natural abundance of cucurbitacins in different natural species, their obtaining and isolation is limited, as a result, an increase in their chemical synthesis has been developed by researchers. Data on cucurbitacins and their anticancer activities were collected from databases such as PubMed/MedLine, TRIP database, Web of Science, Google Scholar, and ScienceDirect and the information was arranged sequentially for a better understanding of the antitumor potential. The results of the studies showed that cucurbitacins have significant biological activities, such as anti-inflammatory, antioxidant, antimalarial, antimicrobial, hepatoprotective and antitumor potential. In conclusion, there are several studies, both in vitro and in vivo reporting this important anticancer/chemopreventive potential; hence a comprehensive review on this topic is recommended for future clinical research.

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In vitro antitumor effect of cucurbitacin E on human lung cancer cell line and its molecular mechanism

Cited by 11 publications

References 36 publications

Cucurbitacin I exhibits anticancer efficacy through induction of apoptosis and modulation of JAK / STAT3 , MAPK / ERK , and AKT / mTOR signaling pathways in HepG2 cell line

Cucurbitacin I exhibits anticancer efficacy through induction of apoptosis and modulation of JAK / STAT3 , MAPK / ERK , and AKT / mTOR signaling pathways in HepG2 cell line

Cucurbitacin E inhibits cellular proliferation and induces apoptosis in melanoma by suppressing HSDL2 expression

Cucurbitacins as potential anticancer agents: new insights on molecular mechanisms

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