Inhibition of Growth of Colon Tumors and Proliferation of HT‐29 Cells by Warburgia ugandensis Extract through Mediating G0/G1 Cell Cycle Arrest, Cell Apoptosis, and Intracellular ROS Generation

Zhang, Yongli; Chen, Guilin; Zhuang, Xiao-Cui

doi:10.1155/2021/8807676

Cited by 35 publications

(8 citation statements)

References 43 publications

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“…This suggests that, besides target-binding initiated signal-transductions, redox-based mechanisms might prominently contribute to an antiproliferative effect on this cell line. This assumption could be supported by recent studies demonstrating that ROS is extensively implicated in drug-induced antiproliferative effects on HT-29 and other colon cancer cells [ 43 , 44 , 53 , 54 , 55 ].…”

Section: Discussionmentioning

confidence: 79%

Synthesis and SAR Analysis of Novel 4-Hydroxytamoxifen Analogues Based on Their Cytotoxic Activity and Electron-Donor Character

et al. 2022

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Utilizing McMurry reactions of 4,4′-dihydroxybenzophenone with appropriate carbonyl compounds, a series of 4-Hydroxytamoxifen analogues were synthesized. Their cytotoxic activity was evaluated in vitro on four human malignant cell lines (MCF-7, MDA-MB 231, A2058, HT-29). It was found that some of these novel Tamoxifen analogues show marked cytotoxicity in a dose-dependent manner. The relative ROS-generating capability of the synthetized analogues was evaluated by cyclic voltammetry (CV) and DFT modeling studies. The results of cell-viability assays, CV measurements and DFT calculations suggest that the cytotoxicity of the majority of the novel compounds is mainly elicited by their interactions with cellular targets including estrogen receptors rather than triggered by redox processes. However, three novel compounds could be involved in ROS-production and subsequent formation of quinone-methide preventing proliferation and disrupting the redox balance of the treated cells. Among the cell lines studied, HT-29 proved to be the most susceptible to the treatment with compounds having ROS-generating potency.

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Section: Discussionmentioning

confidence: 79%

Synthesis and SAR Analysis of Novel 4-Hydroxytamoxifen Analogues Based on Their Cytotoxic Activity and Electron-Donor Character

et al. 2022

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“…Interestingly, the antiproliferative effects of 64 and 73 can be terminated by the addition of the antioxidant N-acetyl cysteine (NAC), suggesting that ROS play a critical role in the mode of action of drimanes by inducing DNA damage. Increased ROS and γH2AX levels were also observed in HT-29 and HCT116 and A549 cells after incubation with extracts of W. ugandensis [130,131]. In addition to that, extracts of W. ugandensis lead to an increase in c-PARP1 concentrations.…”

Section: Ros Generation and Dna Damagementioning

confidence: 80%

Anticancer Activity of Natural and Semi-Synthetic Drimane and Coloratane Sesquiterpenoids

et al. 2022

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Drimane and coloratane sesquiterpenoids are present in several plants, microorganisms, and marine life. Because of their cytotoxic activity, these sesquiterpenoids have received increasing attention as a source for new anticancer drugs and pharmacophores. Natural drimanes and coloratanes, as well as their semi-synthetic derivatives, showed promising results against cancer cell lines with in vitro activities in the low micro- and nanomolar range. Despite their high potential as novel anticancer agents, the mode of action and structure–activity relationships of drimanes and coloratanes have not been completely enlightened nor systematically reviewed. Our review aims to give an overview of known structures and derivatizations of this class of sesquiterpenoids, as well as their activity against cancer cells and potential modes-of-action. The cytotoxic activities of about 40 natural and 25 semi-synthetic drimanes and coloratanes are discussed. In addition to that, we give a summary about the clinical significance of drimane and coloratane sesquiterpenoids.

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“…It is well-known that various molecular pathways in cancer progression in HT-29 cells are activated/suppressed by proteins and various cellular enzymes [ 83 , 84 , 85 ]. The promising results observed in terms of AGE inhibition and the high antioxidant capacities of P. auriculata extracts led us to expose the roles of these extracts in ROS-related and AGE-induced protein pathways in HT-29 cells.…”

Section: Resultsmentioning

confidence: 99%

An In-Depth Study on the Metabolite Profile and Biological Properties of Primula auriculata Extracts: A Fascinating Sparkle on the Way from Nature to Functional Applications

et al. 2022

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The biological activity of the aerial part and rhizomes of Primula auriculata were assessed for the first time. The biological activities (antioxidant properties, enzyme inhibition, and AGE inhibition) as well as the phenolic and flavonoid contents of the ethyl acetate, ethanol, hydro-ethanol and water extracts of P. auriculata aerial parts and rhizomes were determined. Cell viability assays and gelatin zymography were also performed for MMP-2/-9 to determine the molecular mechanisms of action. The gene expression for MMPs was described with RT-PCR. The levels of various proteins, including phospho-Nf-κB, BCL-2, BAX, p-53, and cyclin D1 as well as RAGE were measured using Western blot analysis. The hydro-ethanol extract of the aerial part possessed the highest phenolic (56.81 mg GAE/g) and flavonoid (63.92 mg RE/g) contents. In-depth profiling of the specialized metabolites by ultra-high-performance liquid chromatography—high-resolution mass spectrometry (UHPLC-HRMS) allowed for the identification and annotation of 65 compounds, including phenolic acids and glycosides, flavones, flavonols, chalcones, dihydrochalcones, and saponins. The hydro-ethanol extract of the aerial parts (132.65, 180.87, 172.46, and 108.37 mg TE/g, for the DPPH, ABTS, CUPRAC, and FRAP assays, respectively) and the ethanol extract of the rhizomes (415.06, 638.30, 477.77, and 301.02 mg TE/g, for the DPPH, ABTS, CUPRAC, and FRAP assays, respectively) exhibited the highest free radical scavenging and reducing activities. The ethanol and hydro-ethanol extracts of both the P. auriculata aerial part and rhizomes exhibited higher inhibitory activity against acetylcholinesterase, while the hydro-ethanol extracts (1.16 mmol ACAE/g, for both the aerial part and rhizomes extracts) were more active in the inhibition of α-glucosidase. After the treatment of an HT-29 colorectal cancer cell line with the extracts, the apoptosis mechanism was initiated, the integrity of the ECM was remodeled, and cell proliferation was also taken under control. In this way, Primula extracts were shown to be potential drug sources in the treatment of colorectal cancer. They were also detected as natural MMP inhibitors. The findings presented in the present study appraise the bioactivity of P. auriculata, an understudied species. Additional assessment is required to evaluate the cytotoxicity of P. auriculata as well as its activity in ex vivo systems.

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Inhibition of Growth of Colon Tumors and Proliferation of HT‐29 Cells by Warburgia ugandensis Extract through Mediating G₀/G₁ Cell Cycle Arrest, Cell Apoptosis, and Intracellular ROS Generation

Cited by 35 publications

References 43 publications

Synthesis and SAR Analysis of Novel 4-Hydroxytamoxifen Analogues Based on Their Cytotoxic Activity and Electron-Donor Character

Synthesis and SAR Analysis of Novel 4-Hydroxytamoxifen Analogues Based on Their Cytotoxic Activity and Electron-Donor Character

Anticancer Activity of Natural and Semi-Synthetic Drimane and Coloratane Sesquiterpenoids

An In-Depth Study on the Metabolite Profile and Biological Properties of Primula auriculata Extracts: A Fascinating Sparkle on the Way from Nature to Functional Applications

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