Proapoptotic Effect and Molecular Docking Analysis of Curcumin–Resveratrol Hybrids in Colorectal Cancer Chemoprevention

Moreno-Quintero, Gustavo; Herrera-R, Angie; Yepes, Andrés; Naranjo, Tonny W.; Cardona‐G, Wilson

doi:10.3390/molecules27113486

Cited by 7 publications

(4 citation statements)

References 64 publications

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“…Cells with positive staining for PI were considered dead cells, late apoptotic cells, necroptotic cells or secondary necrotic cells. All assays were repeated twice [ 56 ].…”

Section: Methodsmentioning

confidence: 99%

Synthesis and Chemopreventive Potential of 5-FU/Genistein Hybrids on Colorectal Cancer Cells

et al. 2022

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A series of 5-FU-Genistein hybrids were synthesized and their structures were elucidated by spectroscopic analysis. The chemopreventive potential of these compounds was evaluated in human colon adenocarcinoma cells (SW480 and SW620) and non-malignant cell lines (HaCaT and CHO-K1). Hybrid 4a displayed cytotoxicity against SW480 and SW620 cells with IC50 values of 62.73 ± 7.26 µM and 50.58 ± 1.33 µM, respectively; compound 4g induced cytotoxicity in SW620 cells with an IC50 value of 36.84 ± 0.71 µM. These compounds were even more selective than genistein alone, the reference drug (5-FU) and the equimolar mixture of genistein plus 5-FU. In addition, hybrids 4a and 4g induced time- and concentration-dependent antiproliferative activity and cell cycle arrest at the S-phase and G2/M. It was also observed that hybrid 4a induced apoptosis in SW620 cells probably triggered by the extrinsic pathway in response to the activation of p53, as evidenced by the increase in the levels of caspases 3/8 and the tumor suppressor protein (Tp53). Molecular docking studies suggest that the most active compound 4a would bind efficiently to proapoptotic human caspases 3/8 and human Tp53, which in turn could provide valuable information on the biochemical mechanism for the in vitro cytotoxic response of this compound in SW620 colon carcinoma cell lines. On the other hand, molecular dynamics (MD) studies provided strong evidence of the conformational stability of the complex between caspase-3 and hybrid 4a obtained throughout 100 ns all-atom MD simulation. Molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) analyses of the complex with caspase-3 showed that the interaction between the ligand and the target protein is stable. Altogether, the results suggest that the active hybrids, mainly compound 4a, might act by modulating caspase-3 activity in a colorectal cancer model, making it a privileged scaffold that could be used in future investigations.

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“…Cells with positive staining for PI were considered dead cells, late apoptotic cells, necroptotic cells or secondary necrotic cells. All assays were repeated twice [ 56 ].…”

Section: Methodsmentioning

confidence: 99%

Synthesis and Chemopreventive Potential of 5-FU/Genistein Hybrids on Colorectal Cancer Cells

et al. 2022

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“…For this method, 250,000 cells/well were initially seeded in 6-well culture plates during a 24 h adherence period at 37 • C in a 5% CO 2 atmosphere. After this time, the cells were treated with the respective IC 50 of the hybrid compound and vehicle control for 48 h. After treatment, cells were obtained by mechanical disaggregation, resuspended in a solution with Annexin-V-FLUOS and PI, and incubated for 20 min in the dark before flow cytometry analysis [25].…”

Section: Cell Death Induction By 5-fu/curcumin Hybridsmentioning

confidence: 99%

New Hybrid Scaffolds Based on 5-FU/Curcumin: Synthesis, Cytotoxic, Antiproliferative and Pro-Apoptotic Effect

et al. 2023

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A series of 5-FU-Curcumin hybrids were synthesized, and their structures were elucidated by spectroscopic analysis. The synthesized hybrid compounds were evaluated in different colorectal cancer cell lines (SW480 and SW620) and in non-malignant cells (HaCaT and CHO-K1), to determine their chemopreventive potential. Hybrids 6a and 6d presented the best IC50 value against the SW480 cell line with results of 17.37 ± 1.16 µM and 2.43 ± 0.33 µM, respectively. Similarly, compounds 6d and 6e presented IC50 results of 7.51 ± 1.47 µM and 14.52 ± 1.31 µM, respectively, against the SW620 cell line. These compounds were more cytotoxic and selective than curcumin alone, the reference drug 5-fluorouracil (5-FU), and the equimolar mixture of curcumin and 5-FU. In addition, hybrids 6a and 6d (in SW480) and compounds 6d and 6e (in SW620) induced cell cycle arrest in S-phase, and, compounds 6d and 6e caused a significant increase in the sub-G0/G1 phase population in both cell lines. Hybrid 6e was also observed to induce apoptosis of SW620 cells with a respective increase in executioner caspases 3 and 7. Taken together, these results suggest that the hybrids could actively act on a colorectal cancer model, making them a privileged scaffold that could be used in future research.

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“…The PI fluorescence signal was analyzed with excitation at 488 nm (using a Sapphire laser), and detection at 610 nm. The cell cycle model was fixed with FlowJo 7.6.2 (Ashland, OR, USA), applying the Dean-Jett-Fox model [43].…”

Section: Cell Cycle Analysismentioning

confidence: 99%

“…Cells with double-positive staining for Annexin-V and PI were considered late apoptotic or dead cells, while the single staining with Annexin-V/FITC (Annexin-V/FITC positive) or propidium iodide (PI positive) was considered for early apoptotic or necrotic cells, respectively. Assays were performed twice [43].…”

Section: Cell Death Induction By Resveratrol/hydrazone Hybridsmentioning

confidence: 99%

Resveratrol/Hydrazone Hybrids: Synthesis and Chemopreventive Activity against Colorectal Cancer Cells

et al. 2022

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A series of resveratrol/hydrazone hybrids were obtained and elucidated by spectroscopic analysis. All compounds were evaluated against colorectal cancer cells (SW480 and Sw620) and nonmalignant cell lines (HaCaT and CHO-K1) to establish the selectivity index. Among the hybrids evaluated, compounds 6e and 7 displayed the highest cytotoxic activity with IC50 values of = 6.5 ± 1.9 µM and 19.0 ± 1.4 µM, respectively, on SW480 cells. In addition, hybrid 7 also exhibited activity on SW620 cells with an IC50 value of 38.41 ± 3.3 µM. Both compounds were even more toxic against these malignant cells in comparison to the nonmalignant ones, as evidenced by higher selectivity indices 48 h after treatment. These compounds displayed better activity and selectivity than parental compounds (PIH and Resveratrol) and the reference drug (5-FU). In addition, it was observed that both compounds caused antiproliferative activity probably exerted by cell cycle arrest at the G2/M or G0/G1 phases, with the formation of cells in the subG0/G1 phase. Furthermore, it was noticed that compound 7 induced mitochondrial depolarization in SW480 cells and positive staining for propidium iodide in both cancer cell lines, suggesting cell membrane damage involving either apoptosis or other processes of death.

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Proapoptotic Effect and Molecular Docking Analysis of Curcumin–Resveratrol Hybrids in Colorectal Cancer Chemoprevention

Cited by 7 publications

References 64 publications

Synthesis and Chemopreventive Potential of 5-FU/Genistein Hybrids on Colorectal Cancer Cells

Synthesis and Chemopreventive Potential of 5-FU/Genistein Hybrids on Colorectal Cancer Cells

New Hybrid Scaffolds Based on 5-FU/Curcumin: Synthesis, Cytotoxic, Antiproliferative and Pro-Apoptotic Effect

Resveratrol/Hydrazone Hybrids: Synthesis and Chemopreventive Activity against Colorectal Cancer Cells

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