• Journal of Life Science
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• v.24 no.9
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• pp.1012-1018
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• 2014

Sasa quelpaertensis Nakai (Korean name, Jeju-Joritdae) is one of the most abundant plants on Mt. Halla, Jeju Island, and it has long been used in traditional medicines. Recent studies have reported it as possessing various beneficial functions, including anti-inflammatory, anti-diabetic, anti-hypertension, anti-gastritis, anti-oxidant, and anti-cancer effects. However, the molecular mechanisms of its anti-cancer activity have not been clearly elucidated. In this study, we investigated the anti-cancer effects and mechanism of S. quelpaertensis on human colon cancer HT-29 cells. Cell growth inhibition by S. quelpaertensis was determined by MTT assay. Apoptosis was performed by DNA fragmentation, flow cytometry with propidium iodide staining (PI), and reverse transcription-polymerase chain reaction (RT-PCR) to confirm the anti-apoptotic factors, such as inhibitor of apoptosis (IAP) family members. $NO^{\bullet}$ production was determined by Griess assay. S. quelpaertensis treatment resulted in the time- and dose-dependent inhibition of the cell viability of HT-29 cells by inducing apoptosis, as evidenced by the accumulation of the sub-G1 cell population stained by PI, as well as the ladder-like DNA fragmentation in a dose-dependent manner. S. quelpaertensis-inducing apoptosis was accompanied by the induction of S cell cycle arrests, increasing $NO^{\bullet}$ concentrations, and the down-regulation of IAPs, including X-chromosome-linked IAP (XIAP), cellular IAP-1 (cIAP-1), cIAP-2, and survivin. Taken together, these findings have important implications for future clinical developments of S. quelpaertensis in colon cancer treatment.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.93-100
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• 2014

Background: Curcumin has has been reported to exert anti-inflammatory, anti-oxidation and anti-angiogenic activity in various types of cancer. It has also been shown to induce apoptosis in leukemia cells. We aimed to unravel the role of the redox pathway in Curcumin mediated apoptosis with a panel of human leukemic cells. Materials and Methods: In this study in vitro cytotoxicity of Curcumin was measured by MTT assay and apoptotic effects were assessed by annexin V/PI, DAPI staining, cell cycle analysis, measurement of caspase activity and PARP cleavage. Effects of Curcumin on intracellular redox balance were assessed using fluorescent probes like $H_2DCFDA$, JC1 and an ApoGSH Glutathione Detection Kit respectively. Results: Curcumin showed differential anti-proliferative and apoptotic effects on different human leukemic cell lines in contrast to minimal effects on normal cells. Curcumin induced apoptosis was associated with the generation of intracellular ROS, loss of mitochondrial membrane potential, intracellular GSH depletion, caspase activation. Conclusions: As Curcumin induces programmed cell death specifically in leukemic cells it holds a great promise as a future therapeutic agent in the treatment of leukemia.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.6
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• pp.1636-1639
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• 2005

To develop novel anti-leukemic medicine, we have prepared a Korean traditional medicine, named Hang-baek-Tang, which is composed of 8 kinds of anti-leukemic medicinal plants. The water extracts was examined anti-leukemic activity using the human leukemia cell line, HL-60 cells. HL-60 cells showed the growth inhibition and several apoptotic features, including DNA ladders, morphological changes, by treatment of the cells with Hang-Daek-Tang. We have observed that Hang-baek-Tang induced the activation of caspase-3, caspase-8 and caspase-9. Further molecular analysis demonstrated that Hang-baek-Tang induced cleavage of PARP and increase of hypodiploid (Sub-G1) population in flow cytometric analysis. These results indicate that Hang-baek-Tang has been considered to exert anti-leukemic activity through the procaspase-3 activation pathway.

• Journal of the Korean Society of Food Science and Nutrition
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• v.38 no.10
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• pp.1317-1323
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• 2009

In the present study, we investigated the anti-proliferation activity of Citrus grandis Osbeck peel (CGP) in HL60 (human promyelocytic leukemia) cells. It was found that 80% ethanol extract of CGP could inhibit the cell growth in a dose-dependent manner ($250{\sim}1,000{\mu}g/mL$), which was associated with morphological changes and apoptotic cell death such as depolarized mitochondrial membrane, formation of apoptotic bodies and increased populations of apoptotic sub-G1 phase. The results indicate that CGP extract inhibits the growth of HL60 cancer cells by the induction of apoptosis, which may be mediated by its ability to change the Bcl family proteins and increase the activation of caspase-3 and PARP. Therefore, it is suggested that CGP has the potential to provide a remarkable natural defense against the proliferation of HL60 cells.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.5
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• pp.1108-1117
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• 2007

To investigate the possible mechanism of ${\alpha}-spinasterol$ as a candidate of anti-cancer drug, I examined the effects of ${\alpha}-spinasterol$ on the apoptosis of U937 cells MTT assay, flow cytometric analysis, SDS-polyacrylamide gel electrophoresis, Western blot analysis, and RT-PCR were performed. ${\alpha}-spinasterol$ treatment reduced the cell viablilty of U937 cells in a dose-dependent manner, which was associated with the induction of apoptotic cell death. ${\alpha}-spinasterol$ treatment also reduced the levels of Bcl-xL anti-apoptotic protein expression and increased the levels of caspase-3, p53, pro-apoptotic protein, in U937 cells. After treatment the level of Bcl-xL, anti-apoptotic gene expression was decreased and the level of ICE pro-apoptotic gene expression was increased. These findings suggest that ${\alpha}-spinasterol$ induced the apoptotic cell death via regulation of several growth regulatory gene products. The abbreviations used are: FBS, fetal bovine serum; PBS, phosphate buffered saline; PI, propidium iodide; OD, optical density; DiOC6, 3,3-dihexyloxa carbcyanine iodide; MTT, 3 [4-5-dimethylthiazol-2-yl] -2-diphenyltetrazolium bromide.

• Journal of Life Science
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• v.28 no.4
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• pp.415-420
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• 2018

Schisandra chinensis (Turcz.) Baill. (omija) is often used in Chinese medicine to treat various human diseases, and is known to possess various bioactive components such as schizandrin and gomisin A. In the present study, we prepared ethanol extracts of pomace of Schisandra chinensis (PSC) and investigated their effects on cell viability and expression changes of pro-apoptotic genes such as ATF3, NAG-1 and p21 in human colorectal cancer HCT116 cells. PSC significantly reduced cell viability in a dose-dependent manner, and also dramatically induced the expression of ATF3, NAG-1 and p21 genes, with resveratrol used as a positive control. We also assessed the effects of pure compound schizandrin (SZ) derived from Schisandra chinensis on cell viability and expression of pro-apoptotic genes such as ATF3, NAG-1 and p21. The results showed that SZ also decreased cell viabilities in a dose-dependent manner and increased the expression of ATF3, NAG-1 and p21 genes. In addition, apoptosis was detected in SZ-treated HCT116 cells, which was confirmed with PARP cleavage. PARP cleavage was recovered in part by the transfection of NAG-1 siRNA. The results indicate that NAG-1 is one of the genes responsible for apoptosis induced by SZ. Overall, our findings may contribute to understanding the molecular mechanisms of anti-proliferative and pro-apoptotic activities mediated by PSC and SZ.

• Journal of the Korean Society of Food Science and Nutrition
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• v.39 no.8
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• pp.1119-1125
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• 2010

To evaluate resveratrol as a prostate cancer preventive material, we investigated its anti-proliferative and apoptotic effects in RC-58T/h/SA#4 primary human prostate cancer cells. Resveratrol significantly decreased the number of viable RC-58T/h/SA#4 cells in a dose- and time-dependent manner. Resveratrol showed cytotoxicity against RC-58T/h/SA#4, LNCaP, PC-3 human prostate cancer cells with $IC_{50}$ values of 245, 320 and $340\;{\mu}M$, respectively. However the cytotoxic potential of resveratrol against normal RWPE-1 cells was lower ($IC_{50}=982\;{\mu}M$). Resveratrol induced cell death as evidenced by the increased formation of apoptotic bodies, nuclear condensation, sub-G1 phase, and DNA fragmentation. Resveratrol activated initiator caspases 8, and 9 as well as effector caspase 3 in a dose-dependent manner. Furthermore, the general caspase inhibitor z-VAD-fmk significantly inhibited resveratrol-induced apoptosis compared to cells without treatment. These results clearly indicate that resveratrol-induced apoptosis was dependent on caspase activation. Further, resveratrol modulated the down regulation of Bcl-2 (anti-apoptotic), and Bid. However, the level of Bax (pro-apoptotic) remained unchanged. These results suggest that resveratrol induced apoptosis in RC-58T/h/SA#4 cells via a mitochondrial-mediated caspase-dependent pathway, suggesting therapeutic potential against prostate cancer.

• Journal of the Korean Society of Food Science and Nutrition
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• v.37 no.6
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• pp.714-720
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• 2008

Cordyceps militaris is a medicinal fungus which has been used for patient suffering from cancer in Oriental medicine. It was previously reported that C. militaris extracts are capable of inhibiting tumor growth and inducing apoptosis; however, the anti-poliferative effects of human cancer cells have been poorly understood. In this study, to elucidate the anti-cancer mechanisms of human cancer cells by treatment with aqueous extract of C. militaris (AECM), we investigated the anti-proliferative effects of AECM in human hepatocarcinoma Hep3B cells. AECM treatment inhibited the growth of Hep3B cells and induced the apoptotic cell death in a concentration-dependent manner such as formation of apoptotic bodies and increased populations of apoptotic-sub G1 phase. The induction of apoptosis by AECM was connected with a proteolytic activation of caspase-3 and caspase-8. and concomitant degradation of poly (ADP-ribose) polymerase (PARP) and ${\beta}$-catenin proteins. Furthermore, caspase-3 inhibitor, z-DEVD-fmk, significantly inhibited AECM-induced apoptosis demonstrating the important role of caspase-3 in the bserved cytotoxic effect. Taken together, these findings suggest that AECM-induced inhibition of human hepatocarcinoma cell proliferation is associated with the induction of apoptotic cell death via activation of caspase-3 and C. militaris may have therapeutic potential in human cancer.

• Journal of Life Science
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• v.26 no.2
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• pp.241-246
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• 2016

In the present study, ethanol extracts and their subsequent organic solvent fractions were extracted from the lees of Ehwa Makgeolli containing oriental herbs, a commercialized traditional Korean rice wine, and the prepared lees samples were designated as from KSD-E3-1 to KSD-E3-5. First, their effects on cell viability and on the expression of pro-apoptotic ATF3 and NAG-1 genes in human colorectal HCT116 cells were investigated. Among the treated lees samples, the hexane fraction (KSD-E3-2) and the ethyl acetate fraction (KSD-E3-3) of lees extracts from Ehwa Makgeolli significantly reduced cell viabilities, in a dose dependent manner. The treatment with KSD-E3-2 and KSD-E3-3 also increased the expression of pro-apoptotic NAG-1 and ATF-3 genes and their proteins, which were detected with RT-PCR and Western blot analysis, respectively. In addition, poly-(ADP-ribose) polymerase (PARP) cleavage was detected by treatment with the fraction KSD-E3-3, indicating that KSD-E3-3 could induce apoptosis in HCT116 cells. Interestingly, this PARP cleavage was recovered by transfection of NAG-1 small interfering RNA. The results indicate that NAG-1 is one of the genes responsible for apoptosis induced by the fraction KSD-E3-3 from Ehwa Makgeolli. Overall, the findings may help in understanding the molecular mechanisms of the anti-proliferative and pro-apoptotic activities mediated by the lees of Ehwa Makgeolli.

• Journal of Life Science
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• v.31 no.3
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• pp.321-329
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• 2021

This study examined the growth inhibitory effect of the methanol fraction of maesil (Prunus mume) extract (MMF) on LNCaP, PC-3, and RC-58T human prostate cancer cell lines. Among these cell lines, LNCaP was the most sensitive to the inhibitory effects of MMF. Observation of the morphology and apoptotic body formation in the LNCaP cells revealed morphological changes, nuclear damage, and condensation in response to MMF treatment. The suppressive effect of MMF was related to the intrinsic apoptosis pathway, as indicated by increased expression of the pro-apoptotic proteins Bax, capase-3, capase-9, and PARP and decreased expression of the anti-apoptotic protein Bcl-2. Combined treatment with MMF and the AIF inhibitor N-phenylmalemide (N-PM) indicated that MMF treatment alone had a significant growth suppression effect. The involvement of the extrinsic apoptosis pathway was also confirmed by increased expression of AIF and Endo G. The growth suppression effect of MMF was also significant when compared to the effects of a combination of the PI3K inhibitor LY294002 and MMF. The reduced expression of PI3K, p-Akt, and p-mTOR confirmed the involvement of the PI3K/Akt/ mTOR signaling pathway in regulating the anti-proliferative properties of MMF. In conclusion, the growth suppression effect of MMF in the LNCaP human prostate cancer cell line shows the possibility of using this natural product in functional foods.