Cytotoxic components from the leaves of Erythrophleum fordii induce human acute leukemia cell apoptosis through caspase 3 activation and PARP cleavage

Vo, Phuong Luu; Nguyen, Thuy Duong; Trần, Hương Thanh; Nguyen, Yen Nhi; Doan, Minh Thu; Nguyen, Phi Hung; Liên, Giang Thị Kim; Cuong, To Dao; Tran, Manh Hung

doi:10.1016/j.bmcl.2020.127673

Cited by 18 publications

(12 citation statements)

References 26 publications

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“…Stress-induced DNA damage results in rapid phosphorylation of Ser139 of H2AX by PI3K-like kinases such as DNA-PK, ATM, and ATR [ 35 ]. Olaparib treatment has also been reported to significantly increase the level of p-H2AX [ 36 , 37 ]. Treatment of MCF7 and MDA-MB-231 cells with compound 5u or 5s or Olaparib produced equivalent increases in the level of p-H2AX in both cell lines ( Figure 4 ).…”

Section: Resultsmentioning

confidence: 99%

Design and Activity of Novel Oxadiazole Based Compounds That Target Poly(ADP-ribose) Polymerase

et al. 2022

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Novel PARP inhibitors with selective mode-of-action have been approved for clinical use. Herein, oxadiazole based ligands that are predicted to target PARP-1 have been synthesized and screened for the loss of cell viability in mammary carcinoma cells, wherein seven compounds were observed to possess significant IC50 values in the range of 1.4 to 25 µM. Furthermore, compound 5u, inhibited the viability of MCF-7 cells with an IC50 value of 1.4µM, when compared to Olaparib (IC50 = 3.2 µM). Compound 5s also decreased cell viability in MCF-7 and MDA-MB-231 cells with IC50 values of 15.3 and 19.2 µM, respectively. Treatment of MCF-7 cells with compounds 5u and 5s produced PARP cleavage, H2AX phosphorylation and CASPASE-3 activation comparable to that observed with Olaparib. Compounds 5u and 5s also decreased foci-formation and 3D Matrigel growth of MCF-7 cells equivalent to or greater than that observed with Olaparib. Finally, in silico analysis demonstrated binding of compound 5s towardsthe catalytic site of PARP-1, indicating that these novel oxadiazoles synthesized herein may serve as exemplars for the development of new therapeutics in cancer.

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Section: Resultsmentioning

confidence: 99%

Design and Activity of Novel Oxadiazole Based Compounds That Target Poly(ADP-ribose) Polymerase

et al. 2022

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“…Erythrofordin B isolated from the leaves of Vietnamese Erythrophleum fordii Oliver was tested for cytotoxic activity against human leukemia cancer cells (HL‐60 and KG). It was reported with IC 50 values ranging from 15.2 ± 1.5 to 42.2 ± 3.6 µM and showed apoptotic activity due to the activation of caspase‐3 and caspase‐9 in a dose‐dependent manner for (0–30 µM) for 48 h treatment 54 . Qu et al studied the apoptogenic effect of EFLDO (ent‐3α‐formylabieta‐8(14), 13(15)‐dien‐16,12β‐olide), extracted from the Euphorbia lunulata Bge, in the HepG2 cell line.…”

Section: Role Of Phytochemicals As Caspase Inducers: Natural Semisynt...mentioning

confidence: 98%

Caspase‐driven cancer therapies: Navigating the bridge between lab discoveries and clinical applications

Allani,

Akhilesh,

Tiwari

2024

Cell Biochemistry & Function

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Apoptosis is the cell's natural intrinsic regulatory mechanism of normal cells for programmed cell death, which plays an important role in cancer as a classical mechanism of tumor cell death causing minimal inflammation without causing damage to other cells in the vicinity. Induction of apoptosis by activation of caspases is one of the primary targets for cancer treatment. Over the years, a diverse range of natural, synthetic, and semisynthetic compounds and their derivatives have been investigated for their caspase‐mediated apoptosis‐induced anticancer activities. The review aims to compile the preclinical evidence and highlight the critical mechanistic pathways related to caspase‐induced cell apoptosis in cancer treatment. The focus is placed on the key components of the mechanisms, including their chemical nature, and specific attention is given to phytochemicals derived from natural sources and synthetic and semisynthetic compounds. 180+ compounds from the past two decades with potential as anticancer agents are discussed in this review article. By summarizing the current knowledge and advancements in this field, this review provides a comprehensive overview of potential therapeutic strategies targeting apoptosis in cancer cells. The findings presented herein contribute to the ongoing efforts to combat cancer and stimulate further research into the development of effective and targeted anticancer therapies.

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“…Virtual screening of the bioactive compounds on α-glucosidase [PDB 2ZE0] was carried out using AutoDock Vina software. 14,15 A grid box covering the active protein site was generated using the following parameters: center_x = 8.24; center_y = 26.90; center_z = 23.69; size_x = 25; size_y = 25; and size_z = 25. The docking scores are reported in kcal/mol, and the compounds were ranked by their docking scores.…”

Section: Molecular Dockingmentioning

confidence: 99%

α-Glucosidase Inhibitory Activity and Quantitative Contribution of Phenolic Compounds From Vietnamese Aquilaria crassna Leaves

Nguyen

et al. 2022

Natural Product Communications

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Aquilaria crassna Pierre ex Lecomte, Thymelaeaceae, is cultivated for producing resinous heartwood, also called agarwood. Its leaves are a source of herbal tea in Vietnam due to its rich content of polyphenols. However, the α-glucosidase inhibition activity and the contents of phenolic compounds in leaves of different ages have not yet been determined. In the current study, 7 polyphenols [iriflophenone 3,5-C- β-D-diglucoside (1), iriflophenone 3-C- β-D-glucoside (2), mangiferin (3), iriflophenone 2- O- α-rhamnoside (4), genkwanin 5- O- β-primeveroside (5), genkwanin 4′-methyl ether 5- O- β-primeveroside (6), and genkwanin (7)] were isolated from the leaves of A crassna. Among them, genkwanin (7), an O-methylated flavone, was the most active compound that inhibited α-glucosidase activity, with an IC50 value of 24.0 μM. Molecular docking studies were performed to understand the binding interactions of the active compounds. In addition, a reliable and straightforward reversed-phase HPLC method was developed to determine the content of compounds in different leaves of A crassna. Mangiferin (3) showed the highest content. The contents of 1-4 contributed to the total polyphenolic contents and significantly decreased from the youngest to the oldest leaf. The contents of 5-7 fluctuated through various ages of leaves. Compounds 5 and 6 showed a low accumulation in the first and second leaves, then obtained high contents among middle leaves and declined in the oldest. These results suggested that A crassna and its polyphenols may prevent the development and progression of diabetes through α-glucosidase inhibition. Also, the analysis of the polyphenol content in A crassna may be helpful for tea product manufacture.

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Cytotoxic components from the leaves of Erythrophleum fordii induce human acute leukemia cell apoptosis through caspase 3 activation and PARP cleavage

Cited by 18 publications

References 26 publications

Design and Activity of Novel Oxadiazole Based Compounds That Target Poly(ADP-ribose) Polymerase

Design and Activity of Novel Oxadiazole Based Compounds That Target Poly(ADP-ribose) Polymerase

Caspase‐driven cancer therapies: Navigating the bridge between lab discoveries and clinical applications

α-Glucosidase Inhibitory Activity and Quantitative Contribution of Phenolic Compounds From Vietnamese Aquilaria crassna Leaves

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