Reactive oxygen species accumulation contributes to gambogic acid-induced apoptosis in human hepatoma SMMC-7721 cells

Nie, Fei-Fei; Zhang, Xiaonan; Qi, Qi; Yang, Lan-Yan; Yang, Yong; Liu, Wei; Lu, Na; Wu, Zhao-Qiu; You, Qidong; Guo, Qinglong

doi:10.1016/j.tox.2009.03.010

Cited by 79 publications

(61 citation statements)

References 35 publications

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“…ROS accumulation is known to activate caspase-3 in human hepatoma SMMC-7721 cells (13). The results of the present study indicate that GA increased the amount of activated caspase-3 in a dose-dependent manner.…”

Section: Ros Accumulation Leads To the Activation Of Caspase-3 And CLsupporting

confidence: 59%

“…The molecular structure of GA includes an α,β-unsatured ketone, which is present in certain drugs that induce apoptosis by generating ROS (12) and ROS accumulation contributes to the apoptosis of human hepatoma SMMC-7721 cells treated with GA (13). Based on these theories, we hypothesized that GA has the potential to induce the apoptosis of MM RPMI-8226 cells via ROS accumulation.…”

Section: Introductionmentioning

confidence: 99%

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Effects of gambogic acid on the activation of caspase-3 and downregulation of SIRT1 in RPMI-8226 multiple myeloma cells via the accumulation of ROS

Yang

Chen

et al. 2012

Oncology Letters

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Abstract. Multiple myeloma (MM) is the second most commonly diagnosed hematologic malignancy. Although new drugs, including bortezomib and lenalidomide, have improved the treatment landscape for MM patients, MM remains incurable. Therefore, screening for novel anti-myeloma drugs is necessary. Gambogic acid (GA), the main active ingredient of gamboges secreted from the Garcinia hanburryi tree, has been reported to exhibit potent anticancer activity in certain solid tumors and hematological malignancies, while there are few studies that are available concerning its effects on MM cells. In the present study, we investigated the anticancer activity of GA on the MM RPMI-8226 cells and further studied the underlying mechanisms by which GA affected the cells. RPMI-8226 cells were cultured and the effect of GA on cell proliferation was analyzed using MTT assay. Hoechst 33258 staining was used to visualize nuclear fragmentation, and reactive oxygen species (ROS) levels were detected. GA was found to have a significant, dose-dependent effect on growth inhibition and apoptosis induction in RPMI-8226 cells. This activity is associated with the accumulation of ROS, which contributes to the activation of caspase-3 and the cleavage of poly (ADP-ribose) polymerase (PARP), accompanied with apoptosis in RPMI-8226 cells treated with GA. Mammalian SIRT1, as the closest homolog of the yeast Sir2, was extensively involved in regulating cell processes, including cell senescence, aging and neuronal protection, as well as having anti-apoptotic properties. Moreover, SIRT1 overexpression has been shown to protect cancer cells from chemotherapy and ionizing radiation. In the present study, we demonstrated that GA has the potential to downregulate the expression of SIRT1 via ROS accumulation. In conclusion, our study found that GA is able to induce apoptosis in RPMI-8226 cells via ROS accumulation followed by caspase-3 activation, PARP cleavage and SIRT1 downregulation. These results suggest that GA may have the potential to not only induce apoptosis in MM cells, but also to decrease the relapse rate of MM.

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Section: Ros Accumulation Leads To the Activation Of Caspase-3 And CLsupporting

confidence: 59%

Section: Introductionmentioning

confidence: 99%

Effects of gambogic acid on the activation of caspase-3 and downregulation of SIRT1 in RPMI-8226 multiple myeloma cells via the accumulation of ROS

Yang

Chen

et al. 2012

Oncology Letters

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“…Apoptotic and necrotic cells were quantified using an annexin V-fluorescein isothiocyanate (FITC)-propidium iodide (PI) kit (Institute of Beyotime Biotechnology) and detected using a flow cytometric assay (FACSCalibur; Becton Dickinson) (25).…”

Section: Methodsmentioning

confidence: 99%

Oral Administration of Probiotics Inhibits Absorption of the Heavy Metal Cadmium by Protecting the Intestinal Barrier

Zhai

Tian

Zhang

et al. 2016

Appl Environ Microbiol

153

103

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The heavy metal cadmium (Cd) is an environmental pollutant that causes adverse health effects in humans and animals. Our previous work demonstrated that oral administration of probiotics can significantly inhibit Cd absorption in the intestines of mice, but further evidence is needed to gain insights into the related protection mode. The goal of this study was to evaluate whether probiotics can inhibit Cd absorption through routes other than the Cd binding, with a focus on gut barrier protection. In the in vitro assay, both the intervention and therapy treatments of

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“…Moreover, gambogic acid (11) elevated the phosphorylation of c-Jun-N-terminal protein kinase (JNK) and p38, which was the downstream effect of ROS accumulation. Therefore, accumulation of ROS played an important role in gambogic acid-induced mitochondrial signaling pathway (Nie et al, 2009).…”

Section: Pharmaceutical Biologymentioning

confidence: 99%

Prenylated caged xanthones: Chemistry and biology

Anantachoke

Tuchinda

Kuhakarn

et al. 2011

Pharmaceutical Biology

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Reactive oxygen species accumulation contributes to gambogic acid-induced apoptosis in human hepatoma SMMC-7721 cells

Cited by 79 publications

References 35 publications

Effects of gambogic acid on the activation of caspase-3 and downregulation of SIRT1 in RPMI-8226 multiple myeloma cells via the accumulation of ROS

Effects of gambogic acid on the activation of caspase-3 and downregulation of SIRT1 in RPMI-8226 multiple myeloma cells via the accumulation of ROS

Oral Administration of Probiotics Inhibits Absorption of the Heavy Metal Cadmium by Protecting the Intestinal Barrier

Prenylated caged xanthones: Chemistry and biology

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