Faried A, Kurnia D, Faried LS, Usman N, Miyazaki T, Kato H, Kuwano HAnticancer effects of gallic acid isolated from Indonesian herbal medicine, Phaleria macrocarpa (Scheff.) Boerl, on human cancer cell lines. Int J Oncol 30(3): 605-613

Department of General Surgical Science (Surgery I), Gunma University, Maebashi, Gunma 371-8511, Japan.
International Journal of Oncology (Impact Factor: 3.03). 04/2007; 30(3):605-13. DOI: 10.3892/ijo.30.3.605
Source: PubMed


The natural antioxidant gallic acid (GA) was isolated from fruits of a medicinal Indonesian plant, Phaleria macrocarpa (Scheff.) Boerl. The structure was identified on the basis of spectroscopic analysis and comparison with authentic compound. GA demonstrated a significant inhibition of cell proliferation in a series of cancer cell lines and induced apoptosis in esophageal cancer cells (TE-2) but not in non-cancerous cells (CHEK-1). Observation of the molecular mechanism of apoptosis showed that GA up-regulated the pro-apoptosis protein, Bax, and induced caspase-cascade activity in cancer cells. On the other hand, GA down-regulated anti-apoptosis proteins such as Bcl-2 and Xiap. In addition, GA also induced down-regulation of the survival Akt/mTOR pathway. In non-cancerous cells, we observed delayed expression of pro-apoptosis related proteins. 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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    • "It has been shown that P. macrocarpa fruits displayed cytotoxic effect on HT-29, MCF-7 and Hela cell lines [5]. Faried [39] have isolated gallic acid from the fruits of P. macrocarpa and demonstrated that it could cause cancer cell death in various cancer cells, including the human esophageal cancer (TE-2), gastric cancer (MKN-28), colon cancer (HT-29), breast cancer (MCF-7), cervix cancer (Ca Ski), and malignant brain tumor (CGNH-89 and CGNH-PM). In our study, various cell lines were treated with different concentrations of different sample for 24 hrs, 48 hrs and 72 hrs. "
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    ABSTRACT: The edible fruits of Phaleria macrocarpa (Scheff.) Boerl are widely used in traditional medicine in Indonesia. It is used to treat a variety of medical conditions such as - cancer, diabetes mellitus, allergies, liver and heart diseases, kidney failure, blood diseases, high blood pressure, stroke, various skin diseases, itching, aches, and flu. Therefore, it is of great interest to determine the biochemical and cytotoxic properties of the fruit extracts. The methanol, hexane, chloroform, ethyl acetate, and water extracts of P. macrocarpa fruits were examined for phytochemicals, physicochemicals, flavonols, flavonoids and phenol content. Its nutritional value (A.O.A.C method), antioxidant properties (DPPH assay) and cytotoxicity (MTT cell proliferation assay) were also determined. A preliminary phytochemical screening of the different crude extracts from the fruits of P. macrocarpa showed the presence secondary metabolites such as of flavonoids, phenols, saponin glycosides and tannins. The ethyl acetate and methanol extracts displayed high antioxidant acitivity (IC50 value of 8.15±0.02 ug/mL) in the DPPH assay comparable to that of the standard gallic acid (IC50 value of 10.8±0.02 ug/mL). Evaluation of cytotoxic activity showed that the crude methanol extract possessed excellent anti-proliferative activity against SKOV-3 (IC50 7.75±2.56 µg/mL) after 72 hours of treatment whilst the hexane and ethyl acetate extracts displayed good cytotoxic effect against both SKOV-3 and MDA-MB231 cell lines. The chloroform extract however, showed selective inhibitory activity in the breast cancer cell line MDA-MB231 (IC50 7.80±1.57 µg/mL) after 48 hours of treatment.There was no cytotoxic effect observed in the Ca Ski cell line and the two normal cell lines (MRC-5 and WRL-68). The methanol extract and the ethyl acetate fraction of P. macrocarpa fruits exhibited good nutritional values, good antioxidant and cytotoxic activities, and merits further investigation to identify the specific compounds responsible for these activities.
    Full-text · Article · May 2014 · BMC Complementary and Alternative Medicine
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    • "It has been reported that GA induces cell death in a variety of tumor cells. For example, GA promoted the expression of Bax in TE-2 esophageal tumor cells, and Bax was shown to inhibit the expression of Bcl-2 and Xiap and cause apoptosis (Faried et al., 2007). GA has also been shown to induce apoptosis in 3T3-L1 fibroblasts through endogenous and exogenous apoptotic pathways (Hsu et al., 2007). "
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    ABSTRACT: Aims The activation of hepatic stellate cells (HSCs) in response to liver injury is critical to the development of liver fibrosis, thus, the blockage of the activation of HSC is considered as a rational approach for anti-fibrotic treatment. In this report, we investigated the effects and the underlying mechanisms of gallic acid (GA) in interfering with the activation of HSCs. Main methods The primary cultured rat HSCs were treated with various dose of GA for different time intervals. The morphology, viability, caspase activity, calcium ion flux, calpain I activity, ROS generation and lysosomal functions were then investigated. Key findings GA selectively killed HSCs in both dose and time-dependent manners, while remained no harm to hepatocytes. Besides, caspases were not involved in GA-induced cell death of HSCs. Further results showed that GA toxicity was associated with a rapid burst of reactive oxygen species (ROS) and a subsequent increase of intracellular Ca2 + and calpain activity. Addition of calpain I but not calpain II inhibitor rescued HSCs from GA-induced death. In parallel, pretreatment with antioxidants or an intracellular Ca2 + chelator eradicated GA responses, implying that GA-mediated cytotoxicity was dependent on its pro-oxidative properties and its effect on Ca2 + flux. Furthermore, application of ROS scavengers also reversed Ca2 + release and the disruption of lysosomal membranes in GA-treated HSCs. Significance These results provide evidence for the first time that GA causes selective HSC death through a Ca2 +/calpain I-mediated necrosis cascade, suggesting that GA may represent a potential therapeutic agent to combat liver fibrosis.
    Full-text · Article · Apr 2014 · Life sciences
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    • "Gallic acid is an effective chemopreventive agent in vivo and in vitro(6,7,13). In the first experiment, two major active components, tannic acid and gallic acid, from Chinese gall were compared with its aqueous crude extract. "
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    ABSTRACT: Gallic acid is a trihydroxybenzoic acid, also known as 3,4,5-trihydroxybenzoic acid, which is present in plants worldwide, including Chinese medicinal herbs. Gallic acid has been shown to have cytotoxic effects in certain cancer cells, without damaging normal cells. The objective of the present study was to determine whether gallic acid is able to inhibit human cervical cancer cell viability, proliferation and invasion and suppress cervical cancer cell-mediated angiogenesis. Treatment of HeLa and HTB-35 human cancer cells with gallic acid decreased cell viability in a dose-dependent manner. BrdU proliferation and tube formation assays indicated that gallic acid significantly decreased human cervical cancer cell proliferation and tube formation in human umbilical vein endothelial cells, respectively. Additionally, gallic acid decreased HeLa and HTB-35 cell invasion in vitro. Western blot analysis demonstrated that the expression of ADAM17, EGFR, p-Akt and p-Erk was suppressed by gallic acid in the HeLa and HTB-35 cell lines. These data indicate that the suppression of ADAM17 and the downregulation of the EGFR, Akt/p-Akt and Erk/p-Erk signaling pathways may contribute to the suppression of cancer progression by Gallic acid. Gallic acid may be a valuable candidate for the treatment of cervical cancer.
    Full-text · Article · Dec 2013 · Oncology letters
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