Antiproliferative, Cytotoxic, and Apoptotic Activity of Steroidal Oximes in Cervicouterine Cell Lines

Sánchez-Sánchez, Luis; Hernández-Linares, María Guadalupe; Escobar, María Luisa; López-Muñoz, Hugo; Zenteno, Edgar; Fernández-Herrera, María A.; Guerrero‐Luna, Gabriel; Carrasco-Carballo, Alan; Sandoval‐Ramírez, Jesús

doi:10.3390/molecules21111533

Cited by 23 publications

(21 citation statements)

References 64 publications

(66 reference statements)

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“…In a recent report, using diosgenin as the parent molecule, the authors synthesized two novel steroidal oxime compounds that showed significant antiproliferative activity on cervical cancer cells and human lymphocytes. These compounds induced apoptosis and activated caspase 3 [ 85 ]. In another study Mohammad et al, reported on the anti-proliferative activity of diosgenin and its semi-synthetic derivatives against breast (HBL-100), colon (HCT-116 and HT-19) and lung (A549) cancer cells.…”

Section: Semisynthetic Derivatives Of Diosgenin That Exhibit Anti-mentioning

confidence: 99%

Pro-Apoptotic and Anti-Cancer Properties of Diosgenin: A Comprehensive and Critical Review

et al. 2018

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Novel and alternative options are being adopted to combat the initiation and progression of human cancers. One of the approaches is the use of molecules isolated from traditional medicinal herbs, edible dietary plants and seeds that play a pivotal role in the prevention/treatment of cancer, either alone or in combination with existing chemotherapeutic agents. Compounds that modulate these oncogenic processes are potential candidates for cancer therapy and may eventually make it to clinical applications. Diosgenin is a naturally occurring steroidal sapogenin and is one of the major bioactive compounds found in dietary fenugreek (Trigonella foenum-graecum) seeds. In addition to being a lactation aid, diosgenin has been shown to be hypocholesterolemic, gastro- and hepato-protective, anti-oxidant, anti-inflammatory, anti-diabetic, and anti-cancer. Diosgenin has a unique structural similarity to estrogen. Several preclinical studies have reported on the pro-apoptotic and anti-cancer properties of diosgenin against a variety of cancers, both in in vitro and in vivo. Diosgenin has also been reported to reverse multi-drug resistance in cancer cells and sensitize cancer cells to standard chemotherapy. Remarkably, diosgenin has also been reported to be used by pharmaceutical companies to synthesize steroidal drugs. Several novel diosgenin analogs and nano-formulations have been synthesized with improved anti-cancer efficacy and pharmacokinetic profile. In this review we discuss in detail the multifaceted anti-cancer properties of diosgenin that have found application in pharmaceutical, functional food, and cosmetic industries; and the various intracellular molecular targets modulated by diosgenin that abrogate the oncogenic process.

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Section: Semisynthetic Derivatives Of Diosgenin That Exhibit Anti-mentioning

confidence: 99%

Pro-Apoptotic and Anti-Cancer Properties of Diosgenin: A Comprehensive and Critical Review

et al. 2018

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“…Regarding the effect of compound 2 on the Hep-aRG cell cycle, we also decided to study HepaRG cell proliferation after 72 h using an adapted protocol with carboxyfluorescein succinimidyl ester, a dye that labels cell cytoplasm and is diluted on cell division [53]. HepaRG cells treated with compound 2 had a higher intensity signal than control cells (Figure 7), meaning that they accumulated a lower number of cell divisions and therefore are less proliferative.…”

Section: Cell Survival and Cell Cycle Distribution Evaluationmentioning

confidence: 99%

Δ 9,11 -Estrone derivatives as potential antiproliferative agents: synthesis, in vitro biological evaluation and docking studies

Canário¹,

Matias²,

Brito³

et al. 2020

Comptes Rendus. Chimie

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A series of ∆ 9,11 -estrone derivatives with A-and D-ring modifications has been synthesized and evaluated as antiproliferative agents. The cytotoxicity was assessed in six cell lines (MCF-7, T47-D, LNCaP, HepaRG, Caco-2 and NHDF) by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and a cell cycle distribution analysis was performed by flow cytometry. Some compounds exhibited relevant cytotoxicity, particularly ∆ 9,11 -estrone, which was the most active against HepaRG cells (IC 50 = 6.67 µM). Besides the relevance of the double bond in the C-ring, the presence of a 16E-benzylidene group increased the antiproliferative effect on MCF-7 and T47-D cells. Moreover, the introduction of iodine in positions 2 and 4 of estrone seemed to induce a selective cytotoxicity for HepaRG cells. Flow cytometry experiments evidenced a 34% reduction of HepaRG cell viability after treatment with ∆ 9,11 -estrone and a cell cycle arrest at the G 0 /G 1 phase. Estrogenic activity was also observed for this compound at 0.1 µM in T47-D cells, and molecular docking studies estimated a marked interaction between this compound and the estrogen receptor α.

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“…The arrest of cell cycle progression is one of the strategies used to stop cancer proliferation [ 39 ]. In this context, some studies previously published showed the effect of steroidal and non-steroidal oximes in cell cycle [ 26 , 40 ]. As example, it was evidenced that E1-16-oxime ethers promoted the apoptotic HeLa cell death and modulated the cell cycle progression (arrest at G 1 ), leading to an increase in cellular shrinkage, nuclear condensation, membrane permeability, sub-diploid population and caspase-3 activity [ 15 ].…”

Section: Resultsmentioning

confidence: 99%

“…Of these, among other compounds, interesting results were observed for 3-benzyloxy-16-propionyloximino-13α-methylestrone and 3-(4-methoxybenzyloxy)-16-methoximinoestrone as well as for the unsubstituted oximes 16-oximinoestrone and 3-sulfamoyloxy-16-oximinoestrone [ 15 ]. Sánchez-Sánchez et al [ 26 ] also evidenced the antitumor effects of steroidal sapogenin oximes on HeLa cell lines and showed that the antiproliferative activity was 2.3–2.8 times higher than the observed with diosgenin. More recently, C20 oxime ester derivatives were prepared from 16-dehydropregnenolone acetate and showed cytotoxicity against leukemia (NB4), prostate (PC-3) and HeLa cancer cells [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

New Estrone Oxime Derivatives: Synthesis, Cytotoxic Evaluation and Docking Studies

et al. 2021

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The interest in the introduction of the oxime group in molecules aiming to improve their biological effects is increasing. This work aimed to develop new steroidal oximes of the estrane series with potential antitumor interest. For this, several oximes were synthesized by reaction of hydroxylamine with the 17-ketone of estrone derivatives. Then, their cytotoxicity was evaluated in six cell lines. An estrogenicity assay, a cell cycle distribution analysis and a fluorescence microscopy study with Hoechst 3358 staining were performed with the most promising compound. In addition, molecular docking studies against estrogen receptor α, steroid sulfatase, 17β-hydroxysteroid dehydrogenase type 1 and β-tubulin were also accomplished. The 2-nitroestrone oxime showed higher cytotoxicity than the parent compound on MCF-7 cancer cells. Furthermore, the oximes bearing halogen groups in A-ring evidenced selectivity for HepaRG cells. Remarkably, the Δ9,11-estrone oxime was the most cytotoxic and arrested LNCaP cells in the G2/M phase. Fluorescence microscopy studies showed the presence of condensed DNA typical of prophase and condensed and fragmented nuclei characteristic of apoptosis. However, this oxime promoted the proliferation of T47-D cells. Interestingly, molecular docking studies estimated a strong interaction between Δ9,11-estrone oxime and estrogen receptor α and β-tubulin, which may account for the described effects.

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Antiproliferative, Cytotoxic, and Apoptotic Activity of Steroidal Oximes in Cervicouterine Cell Lines

Cited by 23 publications

References 64 publications

Pro-Apoptotic and Anti-Cancer Properties of Diosgenin: A Comprehensive and Critical Review

Pro-Apoptotic and Anti-Cancer Properties of Diosgenin: A Comprehensive and Critical Review

Δ 9,11 -Estrone derivatives as potential antiproliferative agents: synthesis, in vitro biological evaluation and docking studies

New Estrone Oxime Derivatives: Synthesis, Cytotoxic Evaluation and Docking Studies

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