• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.2329-2334
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• 2014

Curcumin can inhibit proliferation of liver cancer cells by inducing apoptosis, but the specific signaling pathways involved are not completely clear. Here, we report that curcumin inhibited proliferation of MHCC97H liver cancer cells by induction of apoptosis in a concentration dependent manner via stimulating intracellular reactive oxygen species (ROS) generation. Also, we showed that increased intracellular ROS formation activated the TLR-4/MyD-88 signaling pathway, resulting in activation of caspase-8 and caspase-3, which eventually led to apoptosis in MHCC97H cells. These results showed that as an prooxidant, curcumin exerts anti-cancer effects by inducing apoptosis via the TLR-4/MyD-88 signaling pathway.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.2133-2139
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• 2014

4-Methylsulfinyl-3-butenyl isothiocyanate (MTBITC) found in the radish (Raphanus sativus L.), is a wellknown anticancer agent. In this study, the mechanisms of the MTBITC induction of cell apoptosis in human A549 lung cancer cells were investigated. Our PI staining results showed that MTBITC treatment significantly increased the apoptotic sub-G1 fraction in a dose-dependent manner. The mechanism of apoptosis induced by MTBITC was investigated by testing the change of mitochondrial membrane potential (${\Delta}{\Psi}m$), the expression of mRNAs of apoptosis-related genes by RT-PCR, and the activities of caspase-3 and -9 by caspase colorimetric assay. MTBITC treatment decreased mitochondrial membrane potential by down-regulating the rate of Bcl-2/Bax and Bcl-xL/Bax, and activation of caspase-3 and -9. Therefore, mitochondrial pathway and Bcl-2 gene family could be involved in the mechanisms of A549 cell apoptosis induced by MTBITC.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.2885-2889
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• 2013

Goniothalamin is an active compound extracted from Goniothalamus griffithii, a local plant found in northern Thailand. Goniothalamin inhibits cancer cell growth but is also toxic to normal cells. The aims of this study were to identify the cytotoxic effect of goniothalamin and the mechanism of cell death in human HL-60 and U937 cells. Cytotoxicity was determined by MTT assay and cell cycle profiles were demonstrated by staining with propidium iodide (PI) and flow cytometry. Apoptosis was confirmed by staining with annexin V-FITC/propidium iodide (PI) and flow cytometry. Reduction of mitochondrial transmembrane potential was determined by staining with dihexyloxacarbocyanine iodide and flow cytometry and expression of Smac, caspase-8 and -9 was demonstrated by Western blotting. Goniothalamin inhibited growth of HL-60 and U937 cell lines. An increase of SubG1 phase was found in their cell cycle profiles, indicating apoptosis as the mode of cell death. Apoptosis was confirmed by the flip-flop of phosphatidylserine using annexin V-FITC/PI assay in HL60 and U937 cells in a dose response manner. Furthermore, reduction of mitochondrial transmembrane potential was found in both cell types while expression of caspase-8, -9 and Smac/Diablo was increased in HL-60 cells. Taken together, our results indicate that goniothalamin-treated human leukemic cells undergo apoptosis via intrinsic and extrinsic pathways.

• Fisheries and Aquatic Sciences
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• v.21 no.8
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• pp.22.1-22.7
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• 2018

Background: Apoptosis is a process of programmed cell death, and apoptosis defect results in serious diseases such as cancer. Apoptosis induction is one of the key mechanisms of anti-cancer agents. This study was aimed to find anti-prostate cancer compounds from marine-derived fungus Microsporum sp. Results: We found that physcion isolated from the fermentation broth extract of the marine fungus Microsporum sp. strain MFS-YL decreases the cell proliferation of PC3 human prostate cancer cells. Physcion induced cell apoptosis as determined by Annexin V/propidium iodide double staining. Physcion downregulated the anti-apopotoic proteins such as Ras, Bcl-xL, and Bcl-2, whereas upregulated the pro-apoptotic Bax. Physcion also activated caspase-3, caspase-8, and caspase-9. Conclusion: These results suggest that physcion from Microsporum sp. inhibits the proliferation of PC3 human prostate cancer cells via the pathway leading to apoptotic cell death. Physcion may be a potential candidate in the field of anticancer drug discovery against human prostate cancer.

• Journal of Microbiology and Biotechnology
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• v.15 no.3
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• pp.532-536
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• 2005

In the course of our screening for small molecules to inhibit apoptosis of U937 human leukemia cells induced by etoposide ($10\;{\mu}g/ml$), Penicillium sp. F020150 with potent inhibitory activity was selected. The active compound was purified from ethyl acetate extract of the microorganism by Sephadex LH-20 column chromatography and HPLC, and was identified as gentisyl alcohol (2,5-dihydroxybenzyl alcohol) by spectroscopic methods. The compound inhibited caspase-3 induction with $IC_{50}$ value of $3.0\;{\mu}g/ml$ after 8 h of etoposide treatment. The expression levels of caspase-3 and PARP were dose-dependently inhibited by the compound, suggesting that gentisyl alcohol inhibits etoposide-induced apoptosis via downregulation of caspases.

• Animal cells and systems
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• v.16 no.1
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• pp.20-26
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• 2012

Drug-induced parkinsonism has been associated with an increased risk for Parkinson's disease. Antipsychotic drugs have long been known to cause parkinsonian symptoms. However, it remains unclear whether antipsychotics can directly damage the nigrostriatal pathway. In the present study, we investigated the toxicity mechanism of two typical antipsychotics, perphenazine and trifluoperazine, in a human dopaminergic cell line, SH-SY5Y. Perphenazine and trifluoperazine induced mitochondrial damage as evidenced by fragmentation of mitochondria, activation of Bax, cytochrome c release and a decrease in cellular ATP level. In addition, activation of caspase-3 and apoptotic nuclei were observed following the drug treatment. However, pan-caspase inhibitor did not suppress the cell death induced by the antipsychotics, suggesting that the initiated apoptosis was possibly shifted to necrosis upon caspase inhibition. Damaged mitochondria may have induced oxidative stress since the drug-induced cell death was partially suppressed by an antioxidant. Taken together, our results suggest that perphenazine and trifluoperazine can induce apoptotic cell death in a dopaminergic cell line via mitochondrial damage accompanied by oxidative stress.

• The Journal of Korean Obstetrics and Gynecology
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• v.19 no.1
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• pp.155-165
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• 2006

이 연구는 MCF-7 인간 유방암 세포주에 대한 귀출파징탕(歸朮破癥湯) 추출물의 증식억제효과 세포독성효과 세포사 유발효과를 확인하기 위하여 이루어졌다. MCF-7 인간 유방암 세포주는 Dulbecco's modified Eagle's medium/F12 (DMEM/F12)에 10% fetal bovine serum(FBS;Gibco) 와 항생제를 가하여 만든 배지를 이용하여 배양하였고, MCPF-7 세포를 96- well plate에 접종한 후 다양한 농도(0~2000g/ml)의 귀출파징탕(歸朮破癥湯)이 든 배지로 처리하고 다양한 시간(48, 96, 192)동안 배양하여 현미경으로 관찰하고 각각 MTS assay kit를 이용하여 세포생존율을 측정하였다. 세포독성은 Sulforhodamine B assay 방법을 이용해 측정하였고 세포사 과정에서 MCF-7세포에서의 caspase 활성화를 측정하기 위해 Western blotting을 수행하여 poly ADP ribose polymerase(PARP)의 절단을 확인하였다. 실험결과 귀출파징탕(歸朮破癥湯) 추출물에 의한 세포성장 및 독성효과는 시간 및 농도에 비례하는 것으로 나타났고 세포고사과정에서 작용하는 caspase의 전 기질인 PARP 절단량이 귀출파징탕(歸朮破癥湯) 처리 농도와 시간에 비례하여 증가하였다. 이것은 caspase-3가 MCF-7 세포의 성장을 억제하는데 중요한 역할을 수행함을 의미한다. 따라서 귀출파징탕(歸朮破癥湯)은 다양한 기전에 의해서 유방암 세포에 대한 억제효과를 가진다는 것을 인식할 수 있다.

• Korean Journal of Medicinal Crop Science
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• v.23 no.2
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• pp.144-149
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• 2015

The peel of Citrus sunki exhibits multiple biological activities such as anti-oxidant, anti-inflammation and anti-obesity, but little is known about neurodegeneration-related activities. In this study, we investigated the protective effect of ethanolic extract from both immature and mature Citrus sunki peel on neuronal cell death. Treatment of the neuroblastoma cell line SH-SY5Y with $MPP^+$, an inducer of Parkinson disease model, increased cell death in a dose dependent manner. Increased levels of active caspase-3 and cleaved PARP were detected. Treatment with immature Citrus sunki peel extract significantly reduced $MPP^+$-induced neurotoxicity. Cytoprotection with immature Citrus sunki peel extract was associated with a decrease in caspase-3 activation and PARP cleavage. In contrast, mature Citrus sunki peel extract had no significant effects. These data suggest that immature Citrus sunki peel extract may exert anti-apoptotic effect through the inhibition of caspase-3 signaling pathway on $MPP^+$-induced neuronal cell death.

• Journal of Applied Biological Chemistry
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• v.64 no.3
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• pp.237-244
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• 2021

Camellia sinensis, Green tea, contains phenolic compounds that act to scavenge reactive oxygen species (ROS), such as catechin, epicatechin, etc. In contrast with the tea leaf, the bioactivity of its fruit and the fruit peels remains still unclear. This study focused on the effects of fruit and fruit peels of C. sinensis (FC and PC) against oxidative DNA damage in NIH/3T3 cells. The scavenging effects of FC and PC on ROS were assessed using 1,1-diphenyl-2-picryl hydrazyl or 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid radicals. The measurement of ROS in cellular levels was conducted by DCFDA reagent and the protein expression of γ-H2AX, H2AX, cleaved caspase-3, p53, and, p-p53 was analyzed by immunoblotting. The gene expressions of p53 and H2AX were assessed using polymerase chain reaction techniques. The major metabolites of FC and PC were quantitatively measured analyzed and the amounts of phenolic compounds and flavonoids in PC were greater than those in FC. Further, PC suppressed ROS production, which protects the oxidative stress-induced DNA damage through reducing H2AX, p53, and caspase-3 phosphorylation. These results refer that the protective effects of FC and PC are mediated by inhibition of p53 signaling pathways, probably via the bioactivity of phenolic compounds. Thus, FC and PC can serve as a potential antioxidant in DNA damage-associated diseases.

• Asian-Australasian Journal of Animal Sciences
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• v.32 no.5
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• pp.629-636
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• 2019

Objective: The study was designed to determine the cytotoxic effect of gallic acid (GA), obtained by the hydrolysis of tannins, on mice TM4 Sertoli cells apoptosis. Methods: In the present study, non-tumorigenic mice TM4 Sertoli cells were treated with different concentrations of GA for 24 h. After treatment, cell viability was evaluated using WST-1, mitochondrial dysfunction, cells apoptosis and necrosis was detected using JC-1, Hoechst 33342 and propidium iodide staining. The expression levels of Cyclin B1, proliferating cell nuclear antigen (PCNA), Bcl-2-associated X protein (BAX), and Caspase-3 were also detected by quantitative real-time polymerase chain reaction and Western-blotting. Results: The results showed that 20 to $400{\mu}M$ GA inhibited viability of TM4 Sertoli cells in a dose-dependent manner. Treatment with $400{\mu}M$ GA significantly inhibited PCNA and Cyclin B1 expression, however up-regulated BAX and Caspase-3 expression, caused mitochondrial membrane depolarization, activated Caspase-3, and induced DNA damage, thus, markedly increased the numbers of dead cells. Conclusion: Our findings showed that GA could disrupt mitochondrial function and caused TM4 cells to undergo apoptosis and necrosis.