The Antitumor Natural Compound Falcarindiol Disrupts Neural Stem Cell Homeostasis by Suppressing Notch Pathway

Kim, Taejun; Kwon, Hyunji; Kang, Mingyu; Leem, Hyun Hee; Lee, Kyung-Ha; Kim, Do-Yeon

doi:10.3390/ijms19113432

Cited by 14 publications

(13 citation statements)

References 35 publications

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“…To determine the anticancer activity of finasteride, we tested the effect of finasteride on glioblastoma stem-like cells, which has not been demonstrated so far. Previously, we showed that cancer stem-like cell populations were enriched by maintaining cells with serum-free culture media supplemented with epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) [ 14 ]. Under this sphere-forming condition, we treated two different glioblastoma cells, U373 and T98G, with finasteride and temozolomide.…”

Section: Resultsmentioning

confidence: 99%

Antioxidant and Antiproliferative Activity of Finasteride against Glioblastoma Cells

Kim

et al. 2021

Pharmaceutics

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Glioblastoma is an actively growing and aggressive brain tumor with a high propensity of recurrence. Although the surgical removal of tumor mass is the primary therapeutic option against glioblastoma, supportive pharmacotherapy is highly essential due to incredibly infiltrative characteristic of glioblastoma. Temozolomide, an FDA-approved alkylating agent, has been used as a first-line standard pharmacological approach, but several evident limitations were repeatedly reported. Despite additional therapeutic options suggested, there are no medications that successfully prevent a recurrence of glioblastoma and increase the five-year survival rate. In this study, we tested the possibility that finasteride has the potential to be developed as an anti-glioblastoma drug. Finasteride, an FDA-approved medication for the treatment of benign prostate hyperplasia and androgenic alopecia, is already known to pass through the blood–brain barrier and possess antiproliferative activity of prostate epithelial cells. We showed that finasteride inhibited the maintenance of glioma stem-like cells and repressed the proliferation of glioblastoma. Mechanistically, finasteride lowered intracellular ROS level by upregulating antioxidant genes, which contributed to inefficient β-catenin accumulation. Downregulated β-catenin resulted in the reduction in stemness and cell growth in glioblastoma.

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Section: Resultsmentioning

confidence: 99%

Antioxidant and Antiproliferative Activity of Finasteride against Glioblastoma Cells

Kim

et al. 2021

Pharmaceutics

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“…. Falcarinol and falcarindiol have also shown in other studies that they can lead to cell cycle arrest and apoptosis of cancer cells, which may be linked to their alkylating properties as described in the introduction [94,[142][143][144]. For example, it has been demonstrated that falcarindiol is able to induce ER stress in breast cancer cells (MDA-MB-231, MDA-MB-468 and SKBR3) leading to caspase-dependent cell death (apoptosis).…”

Section: Cytotoxic C 17 and C 18 Acetylenic Oxylipins From Other Planmentioning

confidence: 90%

“…In addition, falcarindiol contributed to autophagy-dependent cell death in these breast cancer cells and had synergistic effect with approved cancer drugs 5-fluorouracil and bortezomib in killing breast cancer cells [143]. Finally, it has been shown that falcarindiol may inhibit the growth of cancer stem cells by suppressing the Notch pathway, as demonstrated in neural stem cells [144]. The Notch pathway is vital to tumorigenicity of cancer stem cells, which are the driving force of tumor development [145].…”

Section: Cytotoxic C 17 and C 18 Acetylenic Oxylipins From Other Planmentioning

confidence: 99%

Bioactive C17 and C18 Acetylenic Oxylipins from Terrestrial Plants as Potential Lead Compounds for Anticancer Drug Development

Christensen

2020

Molecules

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Bioactive C17 and C18 acetylenic oxylipins have shown to contribute to the cytotoxic, anti-inflammatory, and potential anticancer properties of terrestrial plants. These acetylenic oxylipins are widely distributed in plants belonging to the families Apiaceae, Araliaceae, and Asteraceae, and have shown to induce cell cycle arrest and/or apoptosis of cancer cells in vitro and to exert a chemopreventive effect on cancer development in vivo. The triple bond functionality of these oxylipins transform them into highly alkylating compounds being reactive to proteins and other biomolecules. This enables them to induce the formation of anti-inflammatory and cytoprotective phase 2 enzymes via activation of the Keap1–Nrf2 signaling pathway, inhibition of proinflammatory peptides and proteins, and/or induction of endoplasmic reticulum stress, which, to some extent, may explain their chemopreventive effects. In addition, these acetylenic oxylipins have shown to act as ligands for the nuclear receptor PPARγ, which play a central role in growth, differentiation, and apoptosis of cancer cells. Bioactive C17 and C18 acetylenic oxylipins appear, therefore, to constitute a group of promising lead compounds for the development of anticancer drugs. In this review, the cytotoxic, anti-inflammatory and anticancer effects of C17 and C18 acetylenic oxylipins from terrestrial plants are presented and their possible mechanisms of action and structural requirements for optimal cytotoxicity are discussed.

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“…Interestingly, falcarindiol (3) has been shown to affect cell proliferation in a biphasic manner (hormesis) thus implying that benefits were achieved at non-toxic concentrations [38]. Recent pharmacological studies confirmed the anticancer activity of 3 against some selected cancer cells such as colonrectal cancer [39], breast cancer [40], and glioblastoma cells [41]. Based on the literature data, we decided to investigate the effects on the cell proliferation of new falcarindiol-derived compounds 4 and 5 compared with falcarindiol (3) and acetyl derivatives 1 and 2.…”

Section: Resultsmentioning

confidence: 99%

Oxygenated C17 polyacetylene metabolites from Algerian Eryngium tricuspidatum L. roots: Structure and biological activity

et al. 2019

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The secondary metabolite pattern of Eryngium tricuspidatum has been found to be dominated by C 17 acetylene oxylipins, according to the chemistry reported in the literature for the genus Eryngium. Two new oxylipins, 11acetoxy-falcarindiol (4) and 1,2-dihydro-11-acetoxy-falcarindiol (5) have been isolated, along with main related polyacetylenes 1-3 and the already known monoterpene aldehydes 6-10, from the petroleum ether extract of roots. The structure and the absolute configuration of compounds 4 and 5 have been determined by spectroscopic methods as well as by comparison with related known compounds. Polyacetylenes 1-4 inhibited significantly the in vitro growth of a series of cancer cell lines, ranging from 0.3 to 29 μM, whereas 5 was inactive.

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The Antitumor Natural Compound Falcarindiol Disrupts Neural Stem Cell Homeostasis by Suppressing Notch Pathway

Cited by 14 publications

References 35 publications

Antioxidant and Antiproliferative Activity of Finasteride against Glioblastoma Cells

Antioxidant and Antiproliferative Activity of Finasteride against Glioblastoma Cells

Bioactive C17 and C18 Acetylenic Oxylipins from Terrestrial Plants as Potential Lead Compounds for Anticancer Drug Development

Oxygenated C17 polyacetylene metabolites from Algerian Eryngium tricuspidatum L. roots: Structure and biological activity

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