496P Alterations of cellular proliferation, apoptosis and autophagy by cucurbitacin B treatment in colon cancer cells

Promkan, Moltira; Dakeng, Sumana; Suebsakwong, Parichat; Suksamrarn, Apichart; Patmasiriwat, Pimpicha

doi:10.1093/annonc/mdv533.15

Cited by 2 publications

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“…18−20 Our previous phytochemical study on T. cucumerina revealed that cucurbitacin B (CuB, Figure 1), the major constituent of the plant, shows potent inhibitory activities on human breast cancer cells (MCF-7, MDA-MB-231, and SKBR-3) 16,21 and colon cancer cells (Caco-2 and SW620). 22 Unfortunately, CuB is also highly toxic against normal cells. This disadvantage hampers the possibility of developing this compound into an anticancer drug.…”

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“…The spectroscopic (IR, 1 H NMR, 13 C NMR, and mass spectra) data of CuB are consistent with those reported. 25−27 CuB showed significant cytotoxic activities against various cancer cells, such as breast cancer, 16,21 colon cancer, 22 human nasopharynx carcinoma cells, 28 nonsmall cell lung cancer, human hepatocellular cells, 29 HeLa cells, and HepG2 cells. 30 CuB upregulated DNA methyltransferase 1 and heavy methylation in the promoters of c-Myc, cyclin D1, and survivin, which consequently downregulated the expression of all these oncogenes, were observed.…”

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confidence: 99%

“…Trichosanthes cucumerina L. (Cucurbitaceae), distributed in many countries of Asia and well-known for its bitter taste, is a Thai medicinal herb. Cucurbitacins, the main components of T. cucumerina , − exhibit a variety of pharmacological effects in vitro and in vivo , such as anticancer, hepatoprotective, cardiovascular, purgative, antiinflammatory, antimicrobial, anthelmintic, CNS effects, and antifertility activities. − Our previous phytochemical study on T. cucumerina revealed that cucurbitacin B (CuB, Figure ), the major constituent of the plant, shows potent inhibitory activities on human breast cancer cells (MCF-7, MDA-MB-231, and SKBR-3) , and colon cancer cells (Caco-2 and SW620) . Unfortunately, CuB is also highly toxic against normal cells.…”

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A Bioreductive Prodrug of Cucurbitacin B Significantly Inhibits Tumor Growth in the 4T1 Xenograft Mice Model

Suebsakwong

Wang

Khetkam

et al. 2019

ACS Med. Chem. Lett.

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Cucurbitacin B (CuB), a highly cytotoxic constituent of the Cucurbitaceae plant, was identified to exhibit potent inhibitory activity against human cancer cells as well as normal cells. This disadvantage hampers the possibility of developing this compound into an anticancer drug candidate. In this work, several bioreductive prodrugs of CuB were designed to reduce toxicity to normal cells while maintaining the cytotoxic effect to cancer cells. Embedded with a bioreductive delivery and cleavable system in cancer tissues, cucurbitacin B-based prodrugs 1, 2, and 3 were synthesized and evaluated by in vitro and in vivo experiments. Compared with the parent CuB, prodrug 1 was found to significantly reduce the toxicity down to 310-fold lower against noncancerous cells. LC-MS analyses show that prodrug 1 efficiently releases the parent compound in the reductase-overexpressed MCF-7 cells. In addition, prodrug 1 shows satisfactory and comparable effectiveness in controlling tumor growth as that by tamoxifen in the 4T1 xenograft mice model.

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A Bioreductive Prodrug of Cucurbitacin B Significantly Inhibits Tumor Growth in the 4T1 Xenograft Mice Model

Suebsakwong

Wang

Khetkam

et al. 2019

ACS Med. Chem. Lett.

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“…It has been reported that CuB can target the Notch signalling pathway to induce apoptosis in CRC HCT116 and SW480 cells ( 11 ). Promkan et al ( 12 ) also reported that CuB induced apoptosis in colon cancer Caco-2 and SW620 cells while triggering autophagy. In addition, CuB may regulate the polarization of tumour-associated M2-type macrophages to inhibit the metastasis and invasion of colon cancer cells through suppression of JAK2/STAT3 signalling ( 13 ).…”

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Cucurbitacin B induces apoptosis in colorectal cells through reactive oxygen species generation and endoplasmic reticulum stress pathways

Huang,

Liang,

Xie

et al. 2023

Exp Ther Med

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Cucurbitacin B (CuB) is a member of the cucurbitacin family, which has shown potent anticancer pharmacological activity. Prolonged or severe endoplasmic reticulum stress (ERS) induces apoptosis; therefore, the present study investigated whether CuB may activate the ERS pathway to induce apoptosis. HT-29 and SW620 colorectal cancer (CRC) cells were treated with a range of concentrations of CuB for 48 h, and the viability and proliferation of cells were determined using Cell Counting Kit 8 (CCK8) and colony formation assays. Subsequently, the appropriate CuB concentration (5 µM) was selected for treatment of CRC cells for 48 h. Western blot analysis was used to measure the expression levels of ERS-related proteins, flow cytometry was used to evaluate apoptosis, the dichlorodihydrofluorescein diacetate fluorescent probe was used to detect reactive oxygen species (ROS) production, and the relationship between ROS and ERS was determined by western blot analysis. Furthermore, flow cytometry was used to evaluate apoptosis after treatment with the ERS inhibitor 4-phenylbutyric acid, the ROS inhibitor N-acetylcysteine and following knockdown of CHOP expression. In addition, western blot analysis was performed to measure Bax and Bcl2 protein expression levels, and a CCK8 assay was performed to evaluate the viability of cells following knockdown of CHOP. Notably, CuB treatment increased apoptosis and inhibited cell proliferation in CRC cell lines, and these effects were mediated by ROS and ROS-regulated activation of the PERK and XBP1 ERS pathways. In conclusion, CuB may induce apoptosis in HT-29 and SW620 CRC cells via ROS and ERS.

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496P Alterations of cellular proliferation, apoptosis and autophagy by cucurbitacin B treatment in colon cancer cells

Cited by 2 publications

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A Bioreductive Prodrug of Cucurbitacin B Significantly Inhibits Tumor Growth in the 4T1 Xenograft Mice Model

A Bioreductive Prodrug of Cucurbitacin B Significantly Inhibits Tumor Growth in the 4T1 Xenograft Mice Model

Cucurbitacin B induces apoptosis in colorectal cells through reactive oxygen species generation and endoplasmic reticulum stress pathways

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