• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.5
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• pp.649-659
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• 2011

To examine the anti-cancer effects of Lepidium virginicum L., the anti-proliferative and pro-apoptotic effects of a water extract of L. virginicum leaves (WELVL) and of L. virginicum roots (WELVR) were investigated in HCT116 human colon carcinoma cells. The treatment of HCT116 cells with WELVL and WELVR resulted in the inhibition of growth and morphological changes in a concentration-dependent manner by inducing apoptosis. The growth inhibition and apoptosis induction by WELVR was stronger than that of WELVL thus, we determined that WELVR was the more optimal extract for this study. The increased apoptotic events in HCT116 cells caused by WELVR were associated with an up-regulation of Fas ligand, Bax, and Bad expression, a down-regulation of Bcl-2, Bcl-$_XL$, and Bid expression, and a decrease in the mitochondrial membrane potential (MMP, ${\Delta}{\psi}m$). WELVR treatment induced the proteolytic activation of caspase-3, -8, and -9, and the degradation of caspase-3 substrate proteins, such as poly (ADP-ribose) polymerase (PARP), ${\beta}$-catenin, and phospholipase C-${\gamma}1$ (PLC-${\gamma}1$). In addition, apoptotic cell death induced by WELVR was correlated with a down-regulation of inhibitors of the apoptosis protein (IAP) family, such as the X-linked inhibitor of apoptosis protein (XIAP), cIAP-1, and cIAP-2. These findings suggest that the WELVR-induced inhibition of cell proliferation is associated with the induction of apoptotic cell death. WELVR may be a potential chemotherapeutic agent for the control of HCT116 human colon carcinoma cells.

• Journal of Life Science
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• v.20 no.7
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• pp.977-982
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• 2010

We investigated the anti-cancer effects of two dibenzocyclooctadiene lignans, gomisin A and gomisin N, isolated from Schizandra chinensis Baill, in human promyelocytic U937 cells. Gomisin N, but not gomisin A, inhibited cell growth in a concentration-dependent manner, which was associated with the induction of G1 arrest of the cell cycle. G1 arrest induced by gomisin N was correlated with down-regulation of cyclin E, cyclin-dependent kinase (Cdk) 2 and Cdk4, and a concomitant up-regulation of Cdk inhibitors such as p16 (INK4A) and p21 (WAF1/CIP1). Furthermore, gomisin N inhibited phosphorylation of retinoblastoma protein (pRB) and p130, and expression of transcription factor E2Fs. The results indicated that growth inhibition by gomisin N is related to cell cycle arrest at G1 in U937 cells and these findings suggest that gomisin N may be a useful chemotherapeutic agent.

• Journal of Korean Neurosurgical Society
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• v.30 no.sup1
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• pp.120-123
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• 2001

Objectives : The present study was performed to analyze results of hydroxyurea treatment for unresectable and recurrent meningiomas as adjuvant chemotherapeutic agent. Material and Methods : Among 87 cases of meningioma patients who treated surgically between Jauary 1988 and December 1997 in our department, unresectable and recurrent cases were 4 cases. Histologically, 3 cases were meningothelial type, 1 case was angiomatous type. Tumor orgin was cerebellopontine angle(CPA) in 3 cases, cavernous sinus in 1 case. Three of 4 cases received radiation treatment. All patients received a daily dosage of 20mg/kg/day of hydroxyurea. Hematological monitorning was performed monthly and tumor measurement was assessed by MR imaging before treatment and every 6 months. Mean follow-up period was 34 months. Rerults : All cases showed no enlargement of tumor mass without any shrinkage. Trigeminal neuralgia in 1 case was improved and external herniation of brain on craniectomy site in 1 case was shrunken. None of the patients had any serious side effects. White blood cell count fell below $3000/{\mu}l$ in 1 case, but recovered 2 weeks later with cessation of medication. Conclusion : Hydroxyurea stopped cell growth by triggering the apoptotic cascade. Our preliminary data indicate that hydroxyurea provides adjuvant medical treatment in patients of unresectable and recurrent meningiomas

• Journal of the Korean Society of Food Science and Nutrition
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• v.35 no.7
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• pp.823-827
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• 2006

The present study describes the preliminary evaluation of the cytotoxic effect from Styela clava (Korean name : miduduk) extracts. S. clava was treated with methanol, ethanol, acetone, and water, then cytotoxic effect of the extracts were evaluated by the MTT reduction assay. The ethanol extracts from S. clava showed the cytotoxic activity on the HT-29 human colon cancer cells. The ethanol extracts was further fractionated with n-hexane, diethyl ether, ethyl acetate, and water according to the degree of polarity. The diethyl ether fraction showed high cytotoxic activity of HT-29 cells. however, the other fractions showed low cytotoxicity. The diethyl ether layer also showed the cytotoxic activity against SW620, HeLa, and MCF-7 cells. These studies support that extracts from S. clava may be a potential candidate as a possible chemotherapeutic agent against human cancer cells.

• Journal of Yeungnam Medical Science
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• v.22 no.2
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• pp.221-240
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• 2005

Background: Doxorubicin has proved to be a useful chemotherapeutic agent especially for osteogenic sarcoma. It induces cancer cell death via apoptosis. Materials and Methods: To explore and analyze the changes of gene expression during doxorubicin induced apoptosis on human osteogenic sarcoma, Saos-2 cell, cDNA microarray was performed. After treatment with doxorubicin, total RNA was purified and expressed genes were investigated with a 17k human cDNA microarray. Results: For analysis of the cDNA microarray, the genes were filtered using the sum of the median value of Cy3 and Cy5 signal intensity of greater than 800. Expression of 264 genes was changed by more than 2 fold, and the expression of 35 genes was changed more than 3 fold after treatment with doxorubicin. The genes were primarily related to cell death, cell growth and maintenance, signal transduction, cellular component, transport, and metabolism. Conclusion: Treatment with doxorubicin induced expressional change of many genes. Some of the genes might be related with apoptosis directly or indirectly. Further study is now needed to characterize these genes.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2019.04a
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• pp.111-111
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• 2019

Glycyrrhizae radix is one of the most frequently prescribed ingredients in Oriental medicine, and G. radix extract has been shown to exert anti-cancer effects. However, the cellular and molecular mechanisms of apoptosis by G. radix are poorly defined. In the present study, it was examined the biochemical mechanisms of apoptosis by water extract of G. radix (WEGR) in human bladder T24 cancer cells. It was found that WEGR could inhibit the cell growth of T24 cells in a dose-dependent manner, which was associated with the induction of apoptotic cell death, as evidenced by the formation of apoptotic bodies, DNA fragmentation and increased populations of annexin-V positive cells. The induction of apoptotic cell death by WEGR was connected with an up-regulation of pro-apoptotic Bax protein expression and down-regulation of anti-apoptotic Bcl-2 and Bcl-xL proteins, and inhibition of apoptosis family proteins (XIAP, cIAP-1 and cIAP-2). In addition, apoptosis-inducing concentrations of WEGR induced the activation of caspase-9, an initiator caspase of the mitochondrial-mediated intrinsic pathway, and caspase-3, accompanied by proteolytic degradation of poly (ADP-ribose)-polymerase. WEGR also induced apoptosis via a death receptor-mediated extrinsic pathway by caspase-8 activation, resulting in the down-regulation of total Bid and suggesting the existence of cross-talk between the extrinsic and intrinsic pathways. Taken together, the present results suggest that WEGR may be a potential chemotherapeutic agent for the control of human bladder cancer cells.

• Journal of Nutrition and Health
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• v.55 no.2
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• pp.240-249
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• 2022

Purpose: Glabridin (GD) is a bio-available isoflavane isolated from the root extract of licorice (Glycyrrhiza glabra L.). It exhibits a variety of pharmacological activities such as anti-inflammatory and anti-oxidant activities. However, extracellular vesicles (EVs) secretion and the anti-cancer mechanism of action remains largely unknown. The present study investigates the anticancer effects of GD by determining the inhibition of EVs secretion in the human breast cancer cell line, MDA-MB-231. Methods: Cell viability, reactive oxygen species (ROS) production, migration, invasion rate, and vascular endothelial growth factor (VEGF) concentration were assessed in MDA-MB-231 cells treated with increasing concentrations of GD (0.1, 1, 5, 10, 20 µM). Subsequently, EV secretion and exosomal DEL-1 protein expression were evaluated to determine the anticancer effects of GD. Results: The results showed that GD significantly inhibited the cell proliferation of MDA-MB-231 cells in a dose- or time-dependent manner. Also, ROS production and apoptosis marker protein cleaved caspase-3 were significantly increased in GD-treated MDA-MB-231, compared to control. Furthermore, GD exposure resulted in significantly decreased not only migration and invasion rates but also the VEGF concentration, thereby contributing to a reduction in angiogenesis. Interestingly, the concentration and number of EVs as well as EV marker proteins, such as CD63 and TSG101, were decreased in GD-treated MDA-MB-231 cells. Markedly, extracellular matrix protein DEL-1 as angiogenesis factor was decreased in EVs from GD-treated MDA-MB-231 cells. Conclusion: This study identifies that the anti-cancer molecular mechanism of GD is exerted via inhibition of angiogenesis and EVs secretion, indicating the potential of GD as a chemotherapeutic agent for breast cancer.

• Journal of Life Science
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• v.34 no.5
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• pp.287-295
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• 2024

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality worldwide, necessitating novel therapeutic strategies. The chemotherapeutic agents used to treat HCC patients are toxic and have serious side effects. Therefore, we investigated the efficacy of anticancer drugs that reduce side effects by targeting tumor cells without causing cytotoxicity in healthy hepatocytes. Berberine, an isoquinoline alkaloid derived from plant compounds, has emerged as a potential candidate for cancer treatment due to its diverse pharmacological properties. The effect of berberine on HepG2 cell viability was determined using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assay. HepG2 cell proliferation was determined through a colony-forming assay. The effects of berberine on HepG2 cell migration were evaluated using a wound-healing assay. Berberine inhibited the proliferation of HepG2 cells, as well as colony formation and migration. Berberine treatment increased the expression of autophagy-related genes and proteins, including Beclin-1 and LC3-II, and elevated the activities and mRNA expression of Caspase-9 and Caspase-3. Additionally, in experiments utilizing the Cell-Derived Xenograft animal model, berberine treatment reduced tumor size and weight in a concentration-dependent manner. These results demonstrate the potential of berberine as a versatile anticancer agent with efficacy in both cellular and animal models of hepatocellular carcinoma. The findings herein shed light on berberine's efficacy against HCC, presenting opportunities for targeted and personalized therapeutic interventions.

• Journal of Life Science
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• v.26 no.3
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• pp.376-386
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• 2016

Apoptosis induction has been proposed as an efficient mechanism by which malignant tumor cells can be removed following chemotherapy. The intrinsic mitochondria-dependent apoptotic pathway is frequently implicated in chemotherapy-induced tumor cell apoptosis. Since DNA-damaging agent (DDA)-induced apoptosis is mainly regulated by the tumor suppressor protein p53, and since more than half of clinical cancers possess inactive p53 mutants, microtubule-damaging agents (MDAs), of which apoptotic effect is mainly exerted via p53-independent routes, can be promising choice for cancer chemotherapy. Recently, we found that the apoptotic signaling pathway induced by MDAs (nocodazole, 17α-estradiol, or 2-methoxyestradiol) commonly proceeded through mitotic spindle defect-mediated prometaphase arrest, prolonged Cdk1 activation, and subsequent phosphorylation of Bcl-2, Mcl-1, and Bim in human acute leukemia Jurkat T cells. These microtubule damage-mediated alterations could render the cellular context susceptible to the onset of mitochondria-dependent apoptosis by triggering Bak activation, Δψm loss, and resultant caspase cascade activation. In contrast, when the MDA-induced Bak activation was inhibited by overexpression of anti-apoptotic Bcl-2 family proteins (Bcl-2 or Bcl-xL), the cells in prometaphase arrest failed to induce apoptosis, and instead underwent mitotic slippage and endoreduplication cycle, leading to formation of populations with 8N and 16N DNA content. These data indicate that cellular apoptogenic mechanism is critical for preventing polyploid formation following MDA treatment. Since the formation of polyploid cells, which are genetically unstable, may cause acquisition of therapy resistance and disease relapse, there is a growing interest in developing new combination chemotherapies to prevent polyploidization in tumors after MDA treatment.

• Applied Biological Chemistry
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• v.49 no.3
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• pp.227-232
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• 2006

Styela clava (also called as rough sea squirt or leathery tunicate) is regarded as native to the northwest Pacific region including Korea and widely distributed in parts of northwestern Europe, North America and Australia. To evaluate Styela clava as a potential bioactive agent, the antioxidant activity of aceton extracts from Styela clava (whole, substance and tunic) was tested by measuring inhibitory effect of $H_2O_2$ induced DNA damage using comet assay. Also, anticancer activity on human colon cancer cell (HT-29) was investigated by MTT reduction assay. The $200\;{\mu}M$ $H_2O_2$ induced DNA damage was inhibited with Styela clava aceton extract in dose dependent manner in human leukocytes. The maximum inhibition was by 62.8, 62.1 and 78.3% at the concentration of $50\;{\mu}g/ml$ of whole, substance and tunic extracts, respectively. The aceton extracts from S. clava were also found to inhibit the growth of human colon cancer cell. The cell proliferation rates decreased to 26.9, 30.6 and 12.0% at the concentration of $500\;{\mu}g/ml$ of whole, substance and tunic extracts, respectively. These results support that aceton extracts from S. clava may be a potential candidate as a possible antimutagenic and chemotherapeutic agent.