Artonin E induces p53-independent G1 cell cycle arrest and apoptosis through ROS-mediated mitochondrial pathway and livin suppression in MCF-7 cells

Etti, Imaobong Christopher; Abdullah, Rasedee; Hashim, Najihah Mohd; Abdul, Ahmad Bustamam; Kadir, Arifah Abdul; Yeap, Swee Keong; Waziri, Peter; Malami, Ibrahim; Lim, Kean Pah; Etti, Christopher Joseph

doi:10.2147/dddt.s124324

Cited by 31 publications

(22 citation statements)

References 48 publications

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“…Mitochondrial membrane permeabilization is one of the important key features of mitochondrial apoptotic pathway [ 18 ]. To measure the mitochondrial membrane potential, U-2OS and MG-63 cell lines were treated with DK1 and exposed to JC-1 dye; a compound that emits red fluorescence when present as aggregates, but fluoresces green when existing as monomers [ 19 ].…”

Section: Resultsmentioning

confidence: 99%

Curcumin Analog DK1 Induces Apoptosis in Human Osteosarcoma Cells In Vitro through Mitochondria-Dependent Signaling Pathway

et al. 2018

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Osteosarcoma is one of the primary malignant bone tumors that confer low survival rates for patients even with intensive regime treatments. Therefore, discovery of novel anti-osteosarcoma drugs derived from natural products that are not harmful to the normal cells remains crucial. Curcumin is one of the natural substances that have been extensively studied due to its anti-cancer properties and is pharmacologically safe considering its ubiquitous consumption for centuries. However, curcumin suffers from a poor circulating bioavailability, which has led to the development of a chemically synthesized curcuminoid analog, namely (Z)-3-hydroxy-1-(2-hydroxyphenyl)-3-phenylprop-2-en-1-one (DK1). In this study, the cytotoxic effects of the curcumin analog DK1 was investigated in both U-2OS and MG-63 osteosarcoma cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and cell death was microscopically examined via acridine orange/propidium iodide (AO/PI) double staining. Flow cytometer analysis including Annexin V/Fluorescein isothiocyanate (FITC), cell cycle analysis and JC-1 were adapted to determine the mode of cell death. Subsequently in order to determine the mechanism of cell death, quantitative polymerase chain reaction (qPCR) and proteome profiling was carried out to measure the expression of several apoptotic-related genes and proteins. Results indicated that DK1 induced U-2 OS and MG-63 morphological changes and substantially reduced cell numbers through induction of apoptosis. Several apoptotic genes and proteins were steadily expressed after treatment with DK1; including caspase 3, caspase 9, and BAX, which indicated that apoptosis occurred through a mitochondria-dependent signaling pathway. In conclusion, DK1 could be considered as a potential candidate for an anti-osteosarcoma drug in the near future, contingent upon its ability to induce apoptosis in osteosarcoma cell lines.

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Section: Resultsmentioning

confidence: 99%

Curcumin Analog DK1 Induces Apoptosis in Human Osteosarcoma Cells In Vitro through Mitochondria-Dependent Signaling Pathway

et al. 2018

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“…The present study, thus, confirmed that ADP extract mediated cell cycle arrest at both S and G2/M phase in HCC cells followed by apoptosis through a TP53-independent pathway. Interestingly, in independent studies, Artonin E, a ruthenium- xanthoxylin complex and a novel analog of varacin C have been reported to induce apoptosis in target cancer cells via a TP53-independent pathway 47–49 . It would be our endeavor in future to evaluate and assess the anticancer activity of ADP-extract via alternative pathways of apoptosis induction in vitro and in vivo .…”

Section: Discussionmentioning

confidence: 99%

Cytostatic and Anti-tumor Potential of Ajwa Date Pulp against Human Hepatocellular Carcinoma HepG2 Cells

Siddiqui

Ahmad

Khan

et al. 2019

Sci Rep

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Ajwa dates (Phoenix dactylifera L.) are used by traditional therapeutic practitioners for several health benefits but most remain to be scientifically validated. In this study, we evaluated the apoptosis-inducing effect of ethanolic extract of Ajwa date pulp (ADP) on human hepatocellular carcinoma (HCC) HepG2 cells. High performance liquid chromatography analysis revealed the presence of polysaccharide β-D-glucan in ADP extract. Treated HCC cells revealed morphological characteristics of apoptosis under phase contrast microscopy. MTT assay demonstrated significant (p < 0.05) dose- and time-dependent inhibition of HCC cell growth. HCC cells were found to be in late apoptotic stage on treatment with higher doses of ADP extract as depicted by acridine orange/ethidium bromide and Annexin V-FITC/PI double stain. Importantly, ADP extract increased the reactive oxygen species level and decreased the mitochondrial membrane potential in treated HCC cells. Flow cytometry analysis demonstrated that ADP extract induced elevation of S and G2/M phases of cell cycle. Moreover, ADP extract induced apoptosis in HCC cells independent of tumor suppressor genes viz. CHEK2, ATM and TP53. Interestingly, ADP extract did not display any significant effect on normal cell line Vero. This study provides validation that ADP extract can be considered as a safe and natural potential drug candidate against human liver cancer.

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“…This may explain the high level of p53 in patients with CML compared to the control patients. Moreover, the mitochondrial p53 gene is able to activate a pro-apoptotic protein that stimulates the release of cytochrome C causing potential apoptosis [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

p53 Gene (NY-CO-13) Levels in Patients with Chronic Myeloid Leukemia: The Role of Imatinib and Nilotinib

2018

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The p53 gene is also known as tumor suppressor p53. The main functions of the p53 gene are an anticancer effect and cellular genomic stability via various pathways including activation of DNA repair, induction of apoptosis, and arresting of cell growth at the G1/S phase. Normally, the p53 gene is inactivated by mouse double minute 2 proteins (mdm2), but it is activated in chronic myeloid leukemia (CML). Tyrosine kinase inhibitors are effective chemotherapeutic agents in the management of CML. The purpose of the present study was to evaluate the differential effect of imatinib and nilotinib on p53 gene serum levels in patients with CML. A total number of 60 patients with chronic myeloid leukemia with ages ranging from 47 to 59 years were recruited from the Iraqi Hematology Center. They started with tyrosine kinase inhibitors as first-line chemotherapy. They were divided into two groups—Group A, 29 patients treated with imatinib and Group B, 31 patients treated with nilotinib—and compared with 28 healthy subjects for evaluation p53 serum levels regarding the selective effect of either imatinib or nilotinib. There were significantly (p < 0.01) high p53 gene serum levels in patients with CML (2.135 ± 1.44 ng/mL) compared to the control (0.142 ± 0.11 ng/mL). Patients with CML that were treated with either imatinib or nilotinib showed insignificant differences in most of the hematological profile (p > 0.05) whereas, p53 serum levels were high (3.22 ± 1.99 ng/mL) in nilotinib-treated patients and relatively low (1.18 ± 0.19 ng/mL) in imatinib-treated patients (p = 0.0001). Conclusions: Nilotinib is more effective than imatinib in raising p53 serum levels in patients with chronic myeloid leukemia.

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Artonin E induces p53-independent G1 cell cycle arrest and apoptosis through ROS-mediated mitochondrial pathway and livin suppression in MCF-7 cells

Cited by 31 publications

References 48 publications

Curcumin Analog DK1 Induces Apoptosis in Human Osteosarcoma Cells In Vitro through Mitochondria-Dependent Signaling Pathway

Curcumin Analog DK1 Induces Apoptosis in Human Osteosarcoma Cells In Vitro through Mitochondria-Dependent Signaling Pathway

Cytostatic and Anti-tumor Potential of Ajwa Date Pulp against Human Hepatocellular Carcinoma HepG2 Cells

p53 Gene (NY-CO-13) Levels in Patients with Chronic Myeloid Leukemia: The Role of Imatinib and Nilotinib

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