Plumbagin induces apoptosis via the p53 pathway and generation of reactive oxygen species in human osteosarcoma cells

Tian, Lei; Yin, Delong; Ren, Ye; Chen, Gong; Chen, Anmin; Guo, Fengjin

doi:10.3892/mmr.2011.624

Cited by 22 publications

(12 citation statements)

References 39 publications

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“…ROS has been reported to play pivotal roles in phytochemical-induced cell cycle arrest and apoptosis [23, 24]. Therefore, whether 6-gingerol induced ROS production in LoVo cells was also analyzed.…”

Section: Resultsmentioning

confidence: 99%

6-Gingerol Inhibits Growth of Colon Cancer Cell LoVo via Induction of G2/M Arrest

Lin

Tsay

2012

Evidence-Based Complementary and Alternative Medicine

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6-Gingerol, a natural component of ginger, has been widely reported to possess antiinflammatory and antitumorigenic activities. Despite its potential efficacy against cancer, the anti-tumor mechanisms of 6-gingerol are complicated and remain sketchy. In the present study, we aimed to investigate the anti-tumor effects of 6-gingerol on colon cancer cells. Our results revealed that 6-gingerol treatment significantly reduced the cell viability of human colon cancer cell, LoVo, in a dose-dependent manner. Further flow cytometric analysis showed that 6-gingerol induced significant G2/M phase arrest and had slight influence on sub-G1 phase in LoVo cells. Therefore, levels of cyclins, cyclin-dependent kinases (CDKs), and their regulatory proteins involved in S-G2/M transition were investigated. Our findings revealed that levels of cyclin A, cyclin B1, and CDK1 were diminished; in contrast, levels of the negative cell cycle regulators p27Kip1 and p21Cip1 were increased in response to 6-gingerol treatment. In addition, 6-gingerol treatment elevated intracellular reactive oxygen species (ROS) and phosphorylation level of p53. These findings indicate that exposure of 6-gingerol may induce intracellular ROS and upregulate p53, p27Kip1, and p21Cip1 levels leading to consequent decrease of CDK1, cyclin A, and cyclin B1 as result of cell cycle arrest in LoVo cells. It would be suggested that 6-gingerol should be beneficial to treatment of colon cancer.

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Section: Resultsmentioning

confidence: 99%

6-Gingerol Inhibits Growth of Colon Cancer Cell LoVo via Induction of G2/M Arrest

Lin

Tsay

2012

Evidence-Based Complementary and Alternative Medicine

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“…PL has been described to bind to the active site of ER-alpha in BRCA1-blocked BG1 ovarian cancer cells [40]. One of the key mechanisms of apoptosis induction by PL has been linked to ROS production in cells [18-19, 28, 41]. It has been shown that the ROS scavengers or inhibitors e.g.…”

Section: Discussionmentioning

confidence: 99%

Cytotoxicity and Apoptosis Induced by a Plumbagin Derivative in Estrogen Positive MCF-7 Breast Cancer Cells

Sagar¹,

Esau²,

Moosa³

et al. 2014

ACAMC

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Plumbagin [5-hydroxy- 2-methyl-1, 4-naphthaquinone] is a well-known plant derived anticancer lead compound. Several efforts have been made to synthesize its analogs and derivatives in order to increase its anticancer potential. In the present study, plumbagin and its five derivatives have been evaluated for their antiproliferative potential in one normal and four human cancer cell lines. Treatment with derivatives resulted in dose- and time-dependent inhibition of growth of various cancer cell lines. Prescreening of compounds led us to focus our further investigations on acetyl plumbagin, which showed remarkably low toxicity towards normal BJ cells and HepG2 cells. The mechanisms of apoptosis induction were determined by APOPercentage staining, caspase-3/7 activation, reactive oxygen species production and cell cycle analysis. The modulation of apoptotic genes (p53, Mdm2, NF-kB, Bad, Bax, Bcl-2 and Casp-7) was also measured using real time PCR. The positive staining using APOPercentage dye, increased caspase-3/7 activity, increased ROS production and enhanced mRNA expression of proapoptotic genes suggested that acetyl plumbagin exhibits anticancer effects on MCF-7 cells through its apoptosis-inducing property. A key highlighting point of the study is low toxicity of acetyl plumbagin towards normal BJ cells and negligible hepatotoxicity (data based on HepG2 cell line). Overall results showed that acetyl plumbagin with reduced toxicity might have the potential to be a new lead molecule for testing against estrogen positive breast cancer.

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“…Indeed, plumbagin has been reported to exert anticancer activity on osteosarcoma cells by inducing proapoptotic signaling and modulating the intracellular ROS that causes induction of apoptosis [92]. Moreover plumbagin-induced AMPK activation might be the key mediator of plumbagin's antitumor activity [93].…”

Section: Antioxidant Therapymentioning

confidence: 99%

Natural Compounds as Modulators of NADPH Oxidases

Maraldi

2013

Oxidative Medicine and Cellular Longevity

107

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Reactive oxygen species (ROS) are cellular signals generated ubiquitously by all mammalian cells, but their relative unbalance triggers also diseases through intracellular damage to DNA, RNA, proteins, and lipids. NADPH oxidases (NOX) are the only known enzyme family with the sole function to produce ROS. The NOX physiological functions concern host defence, cellular signaling, regulation of gene expression, and cell differentiation. On the other hand, increased NOX activity contributes to a wide range of pathological processes, including cardiovascular diseases, neurodegeneration, organ failure, and cancer. Therefore targeting these enzymatic ROS sources by natural compounds, without affecting the physiological redox state, may be an important tool. This review summarizes the current state of knowledge of the role of NOX enzymes in physiology and pathology and provides an overview of the currently available NADPH oxidase inhibitors derived from natural extracts such as polyphenols.

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Plumbagin induces apoptosis via the p53 pathway and generation of reactive oxygen species in human osteosarcoma cells

Cited by 22 publications

References 39 publications

6-Gingerol Inhibits Growth of Colon Cancer Cell LoVo via Induction of G2/M Arrest

6-Gingerol Inhibits Growth of Colon Cancer Cell LoVo via Induction of G2/M Arrest

Cytotoxicity and Apoptosis Induced by a Plumbagin Derivative in Estrogen Positive MCF-7 Breast Cancer Cells

Natural Compounds as Modulators of NADPH Oxidases

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