A Novel Potent Anticancer Compound Optimized from a Natural Oridonin Scaffold Induces Apoptosis and Cell Cycle Arrest through the Mitochondrial Pathway

Lung cancer is the most common type of cancer which the mortality rate increases year by year. Therapeutic drugs could not control the progression of cancer and it contributes to the side effects in normal cells. Thus, an alternative strategy using natural product becomes a focus today. Punica granatum, known as pomegranate has demonstrated the anti-proliferative effect in A549 cells. To further confirm its efficacy, this study aimed to investigate the type of cell death and its pathway in A549 cells. Propium Iodide staining was applied to determine the cell cycle profile changes induced by this juice. The determination of type of cell death was done using Annex in-V staining and later will be analyzed using flow cytometer. The pathway to apoptosis was investigated by determining the caspase- 3, 8 and 9 activities. The findings were supported by mitochondrial membrane permeability assay and cytochrome c release detection which were later analyzed using flow cytometer. This study revealed that pomegranate juice induced cell cycle arrest at G0/G1 phase and apoptosis through intrinsic pathway following 24 h treatment. Pomegranate juice caused loss of mitochondrial membrane permeability after 48 h (p<0.05) exposure and a release of cytochrome c in cytosol after 24 h (p<0.05) and 48 h (p<0.01) exposure in treated A549 cells. In caspases analysis, it was showed that there was activation of caspase-3 following 72 h (p<0.01) treatment and caspase-9 after 48 (p<0.01) and 72 h (p<0.05) exposure in treated A549 cells. It can be concluded that pomegranate juice able to cause A549 cell growth inhibition by inducing cell cycle arrest and apoptosis through mitochondrial pathway.

Download Full-text

Paris Saponin VII Induces Apoptosis and Cell Cycle Arrest in Erythroleukemia Cells by a Mitochondrial Membrane Signaling Pathway

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200615134039 ◽

2020 ◽

Vol 20 ◽

Author(s):

Xin Lin ◽

Babu Gajendran ◽

Krishnapriya M. Varier ◽

Wuling Liu ◽

Jingrui Song ◽

...

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

Mtt Assay ◽

Mitochondrial Membrane ◽

Antimicrobial Activities ◽

Mitochondrial Pathway ◽

S Phase ◽

Phase Cell ◽

Cycle Arrest ◽

Hel Cells

Background and Purpose: Leukemia considered a top-listed ailment, according to WHO, which contributes to the death of a major population of the world every year. Paris Saponin VII (PS), a saponin which was isolated from the roots of Trillium kamtschaticum, from our group, was reported to provide hemostatic, cytotoxic and antimicrobial activities. However, its molecular mechanism underlying the anti-proliferative effects remains unclear. Thus, this study hypothesized to assess that mechanism in PS treated HEL cells. Methods: The MTT assay used to analyze the PS inhibited cell viability in the HEL cells. We further found that PS could induce S phase cell cycle arrest through flow cytometry as well as the western blot analysis of intrinsic and extrinsic apoptotic molecules. Results: The MTT assay showed the IC50 concentration of PS as 0.667μM. The study revealed that PS treatment inhibits cell proliferation dose-dependently. It further caused mitochondrial membrane potential changes by PS treatment. Mechanistic protein expression revealed a dose-dependent upsurge for Bid and Bim molecules, while Bcl2 and PARP expression levels were significantly (P< 0.05) down-regulated in PS treated HEL cells resulting in caspase -3 release and increased the Bim levels upon 24h of incubation. Conclusions: These findings indicate that PS possesses an excellent anti-leukemic activity via regulation of the mitochondrial pathway, leading to S phase cell cycle arrest and caspase-dependent apoptosis suggesting it as a potential alternative chemotherapeutic agent for leukemia patients.

Download Full-text

Induction of apoptosis by magnolol via the mitochondrial pathway and cell cycle arrest in renal carcinoma cells

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2018.12.087 ◽

2019 ◽

Vol 508 (4) ◽

pp. 1271-1278 ◽

Cited By ~ 7

Author(s):

Haiyan Wen ◽

Siqi Zhou ◽

Jinchun Song

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

Renal Carcinoma ◽

Mitochondrial Pathway ◽

Carcinoma Cells ◽

Cycle Arrest ◽

Induction Of Apoptosis ◽

Renal Carcinoma Cells

Download Full-text

Retraction: A Dihydrobenzofuran Lignan Induces Cell Death by Modulating Mitochondrial Pathway and G2/M Cell Cycle Arrest

Journal of Medicinal Chemistry ◽

10.1021/jm4001456 ◽

2013 ◽

Vol 56 (4) ◽

pp. 1787-1787

Author(s):

Julie S. Bose ◽

Vijay Gangan ◽

Ravi Prakash ◽

Swatantra Kumar Jain ◽

Sunil Kumar Manna

Keyword(s):

Cell Cycle ◽

Cell Death ◽

Cell Cycle Arrest ◽

Mitochondrial Pathway ◽

M Cell ◽

Cycle Arrest

Download Full-text

Effect of methoxy stilbenes—analogs of resveratrol—on the viability and induction of cell cycle arrest and apoptosis in human myeloid leukemia cells

Molecular and Cellular Biochemistry ◽

10.1007/s11010-020-03837-0 ◽

2020 ◽

Vol 474 (1-2) ◽

pp. 113-123

Author(s):

Małgorzata Zielińska-Przyjemska ◽

Mariusz Kaczmarek ◽

Violetta Krajka-Kuźniak ◽

Marcin Wierzchowski ◽

Wanda Baer-Dubowska

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

Cell Lines ◽

P53 Protein ◽

Mitochondrial Pathway ◽

Cell Cycle Distribution ◽

Monocytic Leukemia ◽

Cycle Arrest ◽

Bax Protein ◽

Induction Of Apoptosis

Abstract The present study aimed to evaluate the cytotoxicity and its mechanism of five synthetic methoxy stilbenes, namely 3,4,4ʹ-trimethoxy, 3,4,2ʹ-trimethoxy, 3,4,2ʹ,4ʹ-tetramethoxy, 3,4,2ʹ,6ʹ-tetramethoxy, and 3,4,2ʹ,4ʹ,6ʹ-pentamethoxy-trans-stilbenes (MS), in comparison with resveratrol (RSV). Human promyelocytic (HL-60) and monocytic leukemia (THP-1) cells were treated with the tested compounds for 24 h, and cytotoxicity, cell cycle distribution, and apoptosis were evaluated. Significant differences were found in the susceptibility of these cell lines to all stilbenes, including RSV. The THP-1 cells were more resistant to cytotoxic activity of these compounds than HL-60 cells. Among the tested stilbenes, 3,4,4ʹ-tri-MS and 3,4,2ʹ,4ʹ-tetra-MS exhibited higher cytotoxicity toward both cell lines than RSV and the other methoxy stilbenes. This activity might be related to cell cycle arrest at the G2/M phase and induction of apoptosis. In this regard, 3,4,4ʹ-tri-MS and 3,4,2ʹ,4ʹ-tetra-MS at highest concentrations increased the p53 protein level particularly in HL-60 cells. Moreover, treatment with these derivatives increased the ratio of the proapoptotic Bax protein to the antiapoptotic Bcl-xl protein, suggesting the induction of apoptosis through the intrinsic mitochondrial pathway in both cell lines. Further studies are required to fully elucidate the mechanism of these activities.

Download Full-text