Anti-tumor effect of gallic acid on LL-2 lung cancer cells transplanted in mice

Kawada, Miki; Ohno, Yasushi; Ri, Yunmo; Ikoma, Tetsuro; Yuugetu, Hideyuki; Asai, Tomio; Watanabe, Minoru; Yasuda, Norio; Akao, Seigou; Takemura, Genzou; Minatoguchi, Shinya; Gotoh, Kohshi; Fujiwara, Hisayoshi; Fukuda, Kazunori

doi:10.1097/00001813-200111000-00009

Cited by 153 publications

(75 citation statements)

References 20 publications

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“…its various biological activities, such as anti-bacterial (3), anti-viral (4) and anti-inflammatory (5), have been reported, and the anti-cancer activity of Ga has been reported in various types of cancer cells, such as prostate (6), lung (7,8), gastric, colon, breast, cervical and esophageal (9). cell death induced by Ga is associated with oxidative stress derived from reactive oxygen species (roS), mitochondrial dysfunction and an increase in intracellular ca 2+ level (10,11).…”

Section: Introductionmentioning

confidence: 99%

MAPK inhibitors differentially affect gallic acid-induced human pulmonary fibroblast cell growth inhibition

Park

2010

Mol Med Rep

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Abstract. Gallic acid (Ga) has various biological properties, including an anti-cancer effect. However, little is known about the toxicological effect of Ga in primary normal cells in relation to mitogen-activated protein kinase (MaPK) signaling. in this study, we investigated the effects of MaPK (MeK, JnK or p38) inhibitors on Ga-treated human pulmonary fibroblast (HPF) cells in relation to cell growth inhibition, cell death, reactive oxygen species (roS) and glutathione (GSH). GA induced HPF cell growth inhibition and cell death at 24 h, which was accompanied by the loss of mitochondrial membrane potential (MMP; ∆ψ m ). Ga increased roS levels and GSH-depleted cell numbers in the HPF cells. The MEK inhibitor did not affect cell growth inhibition, cell death, roS and GSH levels in the GA-treated HPF cells. The JNK inhibitor slightly enhanced cell growth inhibition by Ga, while the p38 inhibitor significantly prevented the growth inhibition. Both JnK and p38 inhibitors did not affect cell death, roS and GSH levels in the GA-treated HPF cells. In conclusion, MaPK inhibitors differentially affected the growth inhibition of GA-treated HPF cells, which were not related to cell death, roS and GSH levels.

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Section: Introductionmentioning

confidence: 99%

MAPK inhibitors differentially affect gallic acid-induced human pulmonary fibroblast cell growth inhibition

Park

2010

Mol Med Rep

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“…The cells were treated with 200 and 250 μM GA for 0, 12, 24, 48 and 72 h. Cells (1x10 5 cells per sample) were centrifuged at 1000 x g for 5 min, cell pellets were dissolved with 0.5 ml of PBS containing 5 μg/ml PI and viable cells were deter-mined by using FACSCalibur utilizing CellQuest software (Becton-Dickinson, San Jose, CA, USA) for determination of viable cells as previously described (14)(15)(16).…”

Section: Assessment Of Cell Viabilitymentioning

confidence: 99%

“…It was also reported that GA plays an important role in the prevention of malignant transformation (13) and GA prevents amyloid ß-induced apoptotic neuronal death by interfering with the increase of Ca 2+ levels and then by inhibiting glutamate release and generation of ROS (14). GA was shown to have antitumor effects on LL-2 lung cancer cells transplanted in mice (15) and NCI-H460 human lung cancer cells in vitro and in vivo (10). However, there is no study to show that GA affected A375.S2 human melanoma cells.…”

Section: Introductionmentioning

confidence: 98%

Gallic acid induces apoptosis in A375.S2 human melanoma cells through caspase-dependent and -independent pathways

Lai²,

Yang

et al. 2010

Int J Oncol

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Abstract. The natural antioxidant gallic acid (GA) has demonstrated a significant inhibition of cell proliferation and induction of apoptosis in a series of cancer cell lines. However, there is no available information to show whether GA induces apoptosis in human skin cancer cells. In the present study, we report GA-induced apoptosis in A375.S2 human melanoma cells. GA affected morphological changes, decreased the percentage of viable cells and induced apoptosis in A375.S2 cells in a dose-and time-dependent manner. Observation of the molecular mechanism of apoptosis in A375.S2 cells showed that GA up-regulated the proapoptotic proteins such as Bax, and induced caspase cascade activity, but down-regulated antiapoptotic proteins such as Bcl-2. GA induced reactive oxygen species (ROS) and intracellular Ca 2+ productions and decreased the level of mitochondrial membrane potential (Δae m ) in A375.S2 cells in a timedependent manner. GA triggered cytosolic release of apoptotic molecules, cytochrome c, promoted activation of caspase-9 and caspase-3, and ultimately apoptotic cell death. In addition, GA also promoted cytosolic release of apoptosisinducing factor (AIF) and endonuclease G (Endo G). Therefore, GA may also induce apoptosis through a caspaseindependent pathway. Our results suggest that GA might be a potential anticancer compound; however, in depth in vivo studies are needed to elucidate the exact mechanism.

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“…Various biological effects of Ga have been reported, including anti-bacterial (3), anti-viral (4) and anti-inflammatory activities (5). The major point of interest in Ga is related to its anti-cancer activity, which has been reported in various cancer cells, including prostate (6), lung (7,8), gastric, colon, breast, cervical and esophageal cancer (9). apoptosis induced by Ga is associated with oxidative stress derived from reactive oxygen species (roS), mitochondrial dysfunction and an increase in intracellular ca 2+ levels (10,11).…”

Section: Introductionmentioning

confidence: 99%

The MEK inhibitor PD98059 attenuates growth inhibition and death in gallic acid-treated Calu-6 lung cancer cells by preventing glutathione depletion

Han

Moon²,

You³

et al. 2010

Mol Med Rep

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Abstract. Gallic acid (Ga) is widely distributed in various plants and foods and has various biological effects. in this study, we investigated the effects of mitogen-activated protein kinase (MeK, JnK or p38) inhibitors on Ga-induced calu-6 lung cancer cell death in relation to reactive oxygen species (roS) and glutathione (GSH) levels. Ga inhibited the growth of calu-6 cells and induced apoptosis and/or necrosis accompanied by the loss of mitochondrial membrane potential (MMP; ∆ψ m ). roS levels and the number of GSH-depleted cells were observed to be increased at 24 h. MeK inhibitor suppressed cell growth inhibition, death, MMP (∆ψ m ) loss and GSH depletion induced by Ga, but failed to suppress the increase in roS levels. JnK inhibitor also somewhat suppressed cell growth inhibition, MMP (∆ψ m ) loss and GSH depletion induced by Ga, and limited the increase in roS levels. By contrast, p38 inhibitor mildly enhanced Ga-induced cell growth inhibition, MMP (∆ψ m ) loss and the increase in roS levels. in conclusion, MeK inhibitor suppressed Ga-induced cell growth inhibition and death in calu-6 cells. This was related to the prevention of GSH depletion. IntroductionGallic acid (Ga; 3,4,5-triphydroxyl-benzoic acid) is a polyhydroxylphenolic compound that is widely distributed in various plants, fruits and other foods (1), and is very well absorbed by humans (2). Various biological effects of Ga have been reported, including anti-bacterial (3), anti-viral (4) and anti-inflammatory activities (5). The major point of interest in Ga is related to its anti-cancer activity, which has been reported in various cancer cells, including prostate (6), lung (7,8), gastric, colon, breast, cervical and esophageal cancer (9). apoptosis induced by Ga is associated with oxidative stress derived from reactive oxygen species (roS), mitochondrial dysfunction and an increase in intracellular ca 2+ levels (10,11). controversially, Ga has been suggested to have both pro-oxidant and antioxidant properties depending on iron or H 2 o 2 levels in medium and plasma (12,13).There are currently three well-known mitogen-activated protein kinases (MaPKs): extracellular signal regulated kinase (erK1/2), c-Jun n-terminal kinase/stress-activated protein kinase (JnK/SaPK) and p38 kinase (14). each MaP kinase pathway has relatively different upstream activators and specific substrates (15). Multiple lines of evidence demonstrate that JnK and p38 are strongly activated by roS or by a mild oxidative shift in the intracellular thiol/disulfide redox state, leading to apoptosis (16,17). roS are also known to induce erK phosphorylation and to activate the erK pathway (18). in most instances, erK activation has a pro-survival rather than a pro-apoptotic effect (19). Since variations in the level of roS and differences in the function of MAPKs as influenced by ROS may have opposite effects in even the same type of cells, the relationship between roS and MaPKs in terms of cell survival or cell death signaling requires further clarification.understanding the tox...

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Anti-tumor effect of gallic acid on LL-2 lung cancer cells transplanted in mice

Cited by 153 publications

References 20 publications

MAPK inhibitors differentially affect gallic acid-induced human pulmonary fibroblast cell growth inhibition

MAPK inhibitors differentially affect gallic acid-induced human pulmonary fibroblast cell growth inhibition

Gallic acid induces apoptosis in A375.S2 human melanoma cells through caspase-dependent and -independent pathways

The MEK inhibitor PD98059 attenuates growth inhibition and death in gallic acid-treated Calu-6 lung cancer cells by preventing glutathione depletion

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