Anti-proliferative and pro-apoptotic activities of Alpinia oxyphylla on HepG2 cells through ROS-mediated signaling pathway

Zhang, Qiao; Cui, Can; Chen, Congqin; Hu, Xiaolong; Liu, Yahui; Fan, Yanhua; Meng, Wei

doi:10.1016/j.jep.2015.03.073

Cited by 46 publications

(27 citation statements)

References 34 publications

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“…We would therefore predict that mitochondrial rather than nuclear DNA maybe an important target for oxidation because mitochondrial SOD2 expression is reduced by BAR and there was no detectable increase in GSH following BAR exposure. DNA damage has been shown previously to associate with impaired mitochondrial function and cell migration [30] lending support to our observation of an increase in DNA damage, decreased migration and impaired mitochondrial activity in MCF7 cells after BAR treatment.…”

Section: Discussionsupporting

confidence: 91%

Bardoxolone-methyl inhibits migration and metabolism in MCF7 cells

Refaat

Pararasa

Arif

et al. 2017

Free Radical Research

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Bardoxolone-methyl (BAR) is reported to have anti-inflammatory, anti-proliferative and anti-fibrotic effects. BAR activates Nrf2 and may ameliorate oxidative stress through induction of antioxidant genes. However, off-target effects, probably concentration and NFkB-dependent, have limited the clinical use of BAR. Nrf2 regulates expression of antioxidant and mitochondrial genes and has been proposed as a target for both obesity and breast cancer. Therefore, we explored whether BAR can alter migration and proliferation in the MCF7 cell line and whether metabolic function is affected by BAR. Incubation with BAR caused a time-dependent migratory inhibition and an associated decrease in mitochondrial respiration. Both migratory and mitochondrial inhibition by BAR were further enhanced in the presence of fatty acids. In addition to the activation of Nrf2, BAR altered the expression of target mRNA GCLC and UCP1. After 24 h, BAR inhibited both glycolytic capacity, reserve (p < 0.05) and oxidative phosphorylation (p < 0.001) with an associated increase in mitochondrial ROS and loss of intracellular glutathione in MCF7 cells; however, impairment of mitochondrial activity was prevented by N-acetyl cysteine. The fatty acid, palmitate, increased mitochondrial ROS, impaired migration and oxidative phosphorylation but palmitate toxicity towards MCF7 could not be inhibited by N-acetyl cysteine suggesting that they exert effects through different pathways. BAR-activated AKT, induced DNA damage and inhibited cell proliferation. When the proteasome was inhibited, there was loss of BAR-mediated changes in p65 phosphorylation and SOD2 expression suggesting non-canonical NFkB signaling effects. These data suggest that BAR-induced ROS are important in inhibiting MCF7 migration and metabolism by negatively affecting glycolytic capacity and mitochondrial function. ARTICLE HISTORY

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Section: Discussionsupporting

confidence: 91%

Bardoxolone-methyl inhibits migration and metabolism in MCF7 cells

Refaat

Pararasa

Arif

et al. 2017

Free Radical Research

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“…7). Similar to our work, the petroleum ether extract (PEE) of Alpiniae oxyphyllae , a member of the ginger ( Zingiberacea ) family, increased lactate dehydrogenase release, induced apoptosis, disrupted the mitochondrial membrane potential, and elevated intracellular ROS levels in HepG 2 hepatocellular carcinoma cells [27]. The co-addition of NAC prevented the apoptosis induced by the PEE-mediated ROS generation in HepG 2 cells by enhancing the Bax / Bcl-2 ratio, increasing cytochrome c in the cytosol, and activating caspase-3/9 [27].…”

Section: Discussionsupporting

confidence: 64%

Molecular mechanism of cardol, isolated from Trigona incisa stingless bee propolis, induced apoptosis in the SW620 human colorectal cancer cell line

Kustiawan

Lirdprapamongkol

Palaga

et al. 2017

BMC Pharmacol Toxicol

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BackgroundCardol is a major bioactive constituent in the Trigona incisa propolis from Indonesia, with a strong in vitro antiproliferative activity against the SW620 colorectal adenocarcinoma cell line (IC50 of 4.51 ± 0.76 μg/mL). Cardol induced G0/G1 cell cycle arrest and apoptotic cell death. The present study was designed to reveal the mechanism of cardol’s antiproliferative effect and induction of apoptosis.MethodsChanges in cell morphology were observed by light microscopy. To determine whether the mitochondrial apoptotic pathway was involved in cell death, caspase-3 and caspase-9 activities, western blot analysis, mitochondrial membrane potential, and intracellular reactive oxygen species (ROS) levels were assayed.ResultsChanges in the cell morphology and the significantly increased caspase-3 and caspase-9 activities, plus the cleavage of pro-caspase-3, pro-caspase-9 and PARP, supported that cardol caused apoptosis in SW620 cells within 2 h after treatment by cardol. In addition, cardol decreased the mitochondrial membrane potential while increasing the intracellular ROS levels in a time- and dose-dependent manner. Antioxidant treatment supported that the cardol-induced cell death was dependent on ROS production.ConclusionCardol induced cell death in SW620 cells was mediated by oxidative stress elevation and the mitochondrial apoptotic pathway, and these could be the potential molecular mechanism for the antiproliferative effect of cardol.

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“…AOF is a traditional Chinese medicine that exhibits cardioprotective activity against oxidative stress-induced apoptosis [44, 47]. Accumulating evidence demonstrates that AOF possesses diverse pharmacologic effects including antioxidant, anti-inflammatory, antitumor, and antiapoptosis [59–62]. Thus, we expected AOF may provide a recovery effect against cardiac hypertrophy in D-galactose-induced aged rat.…”

Section: Discussionmentioning

confidence: 99%

“…Treatment with AOF in IA rats significantly decreased the hypertrophy-related markers BNP and MYH7 in a dose-dependent manner in cardiomyocytes. Systematic survey on literatures shows that over the past decade at least 80 chemical constituents were reported to be identified from A. oxyphylla that include sesquiterpenes, flavonoids, diarylheptanoids, steroids, volatile oil, and their glycosides [62, 69–78]. Recently, Chen et al [79] evaluated the abundance of nine secondary metabolites in A. oxyphylla capsular fruits, including flavonoids (e.g., tectochrysin, izalpinin, chrysin, apigenin-4′,7-dimethyl ether, and kaempferide), diarylheptanoids (e.g., yakuchinone A, yakuchinone B, and oxyphyllacinol), and sesquiterpenes (e.g., nootkatone).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Cardiac Hypertrophy Effects in D-Galactose-Induced Senescent Hearts byAlpinate Oxyphyllae FructusTreatment

Chang

Lin

et al. 2017

Evidence-Based Complementary and Alternative Medicine

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Aging is a complex physiological phenomenon accelerated by ROS accumulation, with multisystem decline and increasing vulnerability to degenerative diseases and death. Cardiac hypertrophy is a key pathophysiological component that accompanies the aging process. Alpinate Oxyphyllae Fructus (Alpinia oxyphylla MIQ, AOF) is a traditional Chinese medicine, which provides cardioprotective activity against aging, hypertension, and cerebrovascular disorders. In this study, we found the protective effect of AOF against cardiac hypertrophy in D-galactose-induced aging rat model. The results showed that treating rats with D-galactose resulted in pathological hypertrophy as evident from the morphology change, increased left ventricular weight/whole heart weight, and expression of hypertrophy-related markers (MYH7 and BNP). Both concentric and eccentric cardiac hypertrophy signaling proteins were upregulated in aging rat model. However, these pathological changes were significantly improved in AOF treated group (AM and AH) in a dose-dependent manner. AOF negatively modulated D-galactose-induced cardiac hypertrophy signaling mechanism to attenuate ventricular hypertrophy. These enhanced cardioprotective activities following oral administration of AOF reflect the potential use of AOF for antiaging treatments.

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Anti-proliferative and pro-apoptotic activities of Alpinia oxyphylla on HepG2 cells through ROS-mediated signaling pathway

Cited by 46 publications

References 34 publications

Bardoxolone-methyl inhibits migration and metabolism in MCF7 cells

Bardoxolone-methyl inhibits migration and metabolism in MCF7 cells

Molecular mechanism of cardol, isolated from Trigona incisa stingless bee propolis, induced apoptosis in the SW620 human colorectal cancer cell line

Inhibition of Cardiac Hypertrophy Effects in D-Galactose-Induced Senescent Hearts byAlpinate Oxyphyllae FructusTreatment

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