• Journal of Microbiology and Biotechnology
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• v.34 no.7
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• pp.1433-1442
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• 2024

Gastric adenocarcinoma (GAC) is a common, malignant type of tumor in human, and is accompanied with higher mortality. Muscleblind-like 3 (MBNL3) was found to be a pivotal participator in aggravating this cancer's progression. However, the regulatory effects of MBNL3 on GAC development have not been investigated. We therefore sought to study the functions of MBNL3 in GAC progression. In this study, it was demonstrated that MBNL3 exhibited higher expression, and GAC patients with higher MBNL3 expression had poor prognosis. Overexpression of MBNL3 facilitated, and knockdown of MBNL3 suppressed cell proliferation, invasion, and angiogenesis in GAC. Further experiments showed that miR-302e targets MBNL3. Rescue assays then uncovered that the miR-302e/MBNL3 axis aggravated GAC progression. In addition, MBNL3 activated the AKT/VEGFA pathway, and the suppressive regulatory impacts of MBNL3 knockdown on GAC cell proliferation, invasion, and angiogenesis could be rescued after 740 Y-P treatment. Through in vivo assay, it was proved that MBNL3 accelerated tumor growth in vivo. In conclusion, MBNL3 acted as a target of miR-302e to facilitate cell proliferation, invasion, and angiogenesis of gastric adenocarcinoma through the AKT/VEGFA pathway. Our findings illustrate that MBNL3 may be an available bio-target for GAC treatment.

• Journal of Nutrition and Health
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• v.36 no.2
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• pp.133-146
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• 2003

This study was performed to investigate the in vitro and in vivo anticancer effects of persimmon leaf extracts on human gastric cancer cells. In vitro anticancer effects of persimmon leaf extracts (water extract at 8$0^{\circ}C$ for 3 hours, water extract at room temperature for 48 hours, 50% ethanol extract at 8$0^{\circ}C$ for 3 hours, 50% ethanol extract at room temperature for 48 hours, 75% ethanol extract at 8$0^{\circ}C$ for 3 hours and 75% ethanol extract at room temperature for 48 hours) on SNU16 (Korean gastric cancer cell) were investigated by MTT assay. Persimmon leaf extracts exhibited strong in vitro anticancer effects. We found that the higher the ethanol content of the solvent, the stronger the in vitro anticancer effects. Extraction yields, contents of flavonoids, vitamin A, vitamin C and vitamin E were measured. We found that the higher the ethanol content of the solvent, the higher the extraction yields and the contents of flavonoids, vitamin A and vitamin E. Among persimmon leaf extracts, 75% ethanol 8$0^{\circ}C$ extract showed the highest extraction yield, the highest contents of flavonoids, vitamin A and vitamin E and exhibitied the strongest in vitro anticancer effect on SNU16. Therefore, 75% ethanol 8$0^{\circ}C$ extract was chosen as the material to investigate in vivo anticancer effects. In vivo anticancer effect of persimmon leaf 75% ethanol 8$0^{\circ}C$ extract was investigated in SNU16 transplanted nude mice. Twenty five female nude mice (BALB/c) were blocked into five groups according to body weight and raised for 4 weeks with diets containing 4% (w/w), 8% (w/w) persimmon leaf 75% ethanol 8$0^{\circ}C$ extract, with IT (intratumoral) injection treatment with 1.65 mg/100 $\mu$1, 3.3 mg/100 $\mu$1 concentration every other day 3 weeks after SNU16 was transplanted. Persimmon 75% ethanol 8$0^{\circ}C$ extract significantly lowered tumor weight and tumor volume in SNU16 transplanted nude mice. Tumor weight and tumor volume in all experimental groups were significantly lower than those in the control group. Helper T cell (CD4) levels of mice injected with 3.3 mg/100 $\mu$1 extract significantly increased. Cytotoxic T cell (CD8) levels in all experimental groups significantly increased and helper/cytotoxic T cell ratios in all experimental groups significantly decreased. Natural killer cell and MHC class II molecule in all experimental groups significantly increased. In conclusion, persimmon leaf 75% ethanol 8$0^{\circ}C$ extract exhibited strong in vitro and in vivo anticancer effects against SNU16 cells and it increased cytotoxic T cell, natural killer cell and MHC classII molecule in experimental groups in SNU16 transplanted nude mice.

• Korean Journal of Medicinal Crop Science
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• v.12 no.1
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• pp.36-42
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• 2004

The immune activation and anticancer activities of the water and ethanol extracts from Artemisia capillaris Thunb. were studied. The growth of human hepatocarcinoma and human gastric cancer cell was inhibited by the addition of $1.0\;mg/m{\ell}$ of the water extract, by about 77% and 95%, respectively. The growth of human breast cancer cells was also inhibited by addition of $0.5\;mg/m{\ell}$ of both water and ethanol extracts by 88%. The growth of human normal lung cell, HEL299 was inhibited by 15% indicating very low cytotoxicity of both extracts. Overall selectivity of the both extracts on several human cancer cell line was over 2.5. The growth of both human B and T cells was enhanced up to 1.6 to 2.1 times by adding the ethanol extracts. The secretion of cytokines, $TNF-{\alpha}$ and IL-6, from human B cells was also increased showing $68\;pg/m{\ell}$ and $67\;pg/m{\ell}$, respectively, compared to $35{\sim}40\;pg/m{\ell}$ of the control. In terms of the immune activity, there was not much difference between water and ethanol extracts of Artemisia capillaris Thunb. It implies that the extraction solvent could not differ the biological activities of the extracts. Based on these results, Artemisia capillaris Thunb. can be developed into a potentially useful cancer chemoprentive agent.

• Journal of Life Science
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• v.25 no.11
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• pp.1235-1243
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• 2015

Hwangheuk-san (HHS) is a Korean multi-herb formula comprising four medicinal herbs. HHS, which was recorded in “Dongeuibogam,” has been used to treat patients with inflammation syndromes and digestive tract cancer for hundreds of years. However, little is known about its anti-tumor efficacy. The present study investigated the pro-apoptotic effect and mode of action of HHS against AGS human gastric carcinoma cells. HHS inhibited the cell growth of AGS cells in a dose-dependent manner, which was associated with the induction of apoptotic cell death, as evidenced by the formation of apoptotic bodies, chromatin condensation, and an accumulation of cells in the sub-G1 phase. HHS-induced apoptotic cell death was associated with the up-regulation of pro-apoptotic Bax protein expression, down-regulation of antiapoptotic Bcl-2 protein, and the release of cytochrome c from mitochondria to the cytosol. The treatment of AGS cells with HHS significantly elevated the generation of reactive oxygen species (ROS). Additionally, apoptosis-inducing concentrations of HHS induced the activation of both caspase-9 and -8, initiator caspases of the mitochondrial-mediated intrinsic and death receptor-mediated extrinsic pathways, respectively, and caspase-3, accompanied by proteolytic degradation of poly (ADP-ribose)-polymerase. However, ROS scavenger and pan-caspases inhibitor significantly blocked HHS-induced growth inhibition and apoptosis. Taken together, these findings suggest that HHS induces apoptosis through ROS- and caspase-dependent mechanisms and that HHS may be a potential chemotherapeutic agent for the control of human gastric cancer.

• Journal of Pharmacopuncture
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• v.18 no.2
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• pp.26-32
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• 2015

Objectives: Rheum undulatum L. has traditionally been used for the treatment of many diseases in Asia. However, its anti-proliferative activity in cancer has still not been studied. In the present study, we investigated the anti-cancer effects of methanol extract of Rheum undulatum L. (MERL) on human adenocarcinoma gastric cell lines (AGS). Methods: To investigate the anti-cancer effect of MERL on AGS cells, we treated the AGS cells with varying concentrations of MERL and performed 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays. Cell cycle analyses, measurements of the mitochondrial membrane potential (MMP), caspase activity assays and Western blots were conducted to determine whether AGS cell death occurred by apoptosis. Results: Treatment with MERL significantly inhibited growth of AGS cells in a concentration dependent manner. MERL treatment in AGS cells leaded to increased accumulation of apoptotic sub G1 phase cells in a concentration dependent manner. In control cultures, 5.38% of the cells were in the sub G1 phase. In MERL treated cells, however, this percentage was significantly increased (9.95% at $70{\mu}g/mL$, 15.94% at $140{\mu}g/mL$, 26.56% at $210{\mu}g/mL$ and 38.08% at $280{\mu}g/mL$). MERL treatment induced the decreased expression of pro-caspase-8 and -9 in a concentration dependent manner, whereas the expression of the active form of caspase-3 was increased. A subsequent Western blot analysis revealed increased cleaved levels of poly (ADP-ribose) polymerase (PARP) protein. Also, treatment with MERL increased the activities of caspase-3 and -9 compared with the control. MERL treatment increased the levels of the pro-apoptotic truncated Bid (tBid) and Bcl2 Antagonist X (Bax) proteins and decreased the levels of the anti-apoptotic B-cell lymphoma 2 (Bcl-2) protein, whose is the stabilization of mitochondria. However, inhibitions of p38, extracellular signal regulated kinases (ERKs) and C-Jun N-terminal kinases (JNK) by MERL treatment did not affect cell death. Conclusion: These results suggest that MERL mediated cell death is associated with an intrinsic apoptotic pathway in AGS cells.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.3
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• pp.283-291
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• 1999

We have synthesized novel platinum (II) coordination complex containing cis-1,2-diaminocyclohexane (DACH) as a carrier ligand and 1,2-bis(diphenylphosphino)ethane (DPPE) as leaving group. Furthermore, nitrate was added to improve the water-solubility. A new series of [Pt(cis-DACH)(DPPE)] $2NO_3(PC)$ was evaluated its antitumor activity on various MKN-45 human gastric adenocarcinoma cell-lines and normal primary cultured kidney cells. The new platinum complex demonstrated high efficacy in the cytotoxicity on MKN-45 cell-lines as well as adriamycin-resistant (MKN-45/ADR) and cisplatin-resistant (MKN-45/CDDP) cells. The cytotoxicities of PC were found quite less than those of cisplatin in rabbit proximal renal tubular cells, human renal cortical cells and human renal cortical tissues using MTT assay, $[^3H]-thymidine$ uptake and glucose consumption tests. Based on these results, this novel platinum (II) coordination complex, was considered as better a valuable lead for improving antitumor activities with low nephrotoxicities in the development of a new clinically available anticancer chemotherapeutic agents.

• Applied Biological Chemistry
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• v.47 no.2
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• pp.202-207
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• 2004

This study was performed to investigate the inhibitory effect of the water-extract from fermented compositions containing Inonotus obliquus with added Houttuynia cordata on the growth of either human AGS gastric and HCT-15 colon cancer cells or NIH3T3 normal mouse fibroblast cells. Cytotoxic activity on cancer cells was investigated by viable cell count, MTT assay and morphological observation. Mixtures of Inonotus obliquus with added Houttuynia cordata were fermented at $30{\sim}37^{\circ}C$, $50{\sim}60%$ humidity for 30 days, extracted with water, freeze dried, powered, and then dissolved in water for the experiment. In MTT assay, the fermented compositions exhibited inhibitory effects of 13, 25, 40, 67 and 78% for AGS and 22, 40, 50, 69 and 76% for HCT-15 at 0.16, 0.4, 0.8, 1.6 and 4.0 mg/ml, respectively. However, normal NIH3T3 cells were exhibited 86% survival under the same experimental condition. Fermented compositions showed highly inhibitory effect against human cancer cell line HCT-15 and AGS, but not on normal cell line NIH3T3.

• Korean Journal of Pharmacognosy
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• v.25 no.4 s.99
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• pp.382-387
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• 1994

Antineoplastic activity against human gastric and colon carcinoma cell lines was measured in 49 extracts from 46 plants using MTT (3-[4, 5-dimethyl thiazol-2-yl]-2, 5-diphenyl tetrazolium bromide) method. Six extracts from five plants have been reported to have antineoplastic effect. Extracts from remaining 41 plants failed to show significant cytotoxic effect at the concentration of less than $230\;{\mu}g/ml$.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5339-5343
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• 2012

The induction of apoptosis in target cells is a key mechanism for most anti-tumor therapies. Bufalin is a cardiotonic steroid that has the potential to induce differentiation and apoptosis of tumor cells. Research on bufalin has so far mainly involved leukemia, prostate cancer, gastric cancer and liver cancer, and has been confined to in vitro studies. The bufadienolides bufalin and cinobufagin have been shown to induce apoptosis in a wide spectrum of cancer cell. The present article reviews the anticancer effects of bufalin. It induces apoptosis of lung cancer cells via the PI3K/Akt pathway and also suppressed the proliferation of human non-small cell lung cancer A549 cell line in a time and dose dependent manner. Bufalin, bufotalin and gamabufotalin, key bufadienolides, significantly sensitize human breast cancer cells with differing ER-alpha status to apoptosis induction by the TNF-related apoptosis-inducing ligand (TRAIL). In addition, bufadienolides induce prostate cancer cell apoptosis more significantly than that in breast epithelial cell lines. Similar effects have been observed with hepatocellular carcinoma (HCC) but the detailed molecular mechanisms of inducing apoptosis in this case are still unclear. Bufalin exerts profound effects on leukemia therapy in vitro. Results of multiple studies indicate that bufalin has marked anti-tumor activities through its ability to induce apoptosis. Large-scale randomized, double-blind, placebo or positive drug parallel controlled studies are now required to confirm the efficacy and apoptosis-inducing potential of bufalin in various cancers in the cliniucal setting.

• Korean Journal of Food Science and Technology
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• v.30 no.1
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• pp.213-217
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• 1998

This study was performed to observe cytotoxic effect of the pine needle extracts against cancer cell lines including human gastric carcinoma (KATOIII), human lung carcinoma (A549), human hepatocellular carcinoma (Hep3B) and human breast adenocarcinoma (MCF-7) using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) and SRB (sulforhodamine B) method. The extracts were prepared by step-wise fractionation of ethanol extract of pine needles using diethylether, chloroform, ethylacetate, butanol and water. The growth of the cancer cells in medium containing pine needle extracts were significantly inhibited degree in proportion to the increase of the extract concentration. A significant shrinkage of Hep3B cells was observed when the cells were exposed into 0.5, 1 mg/mL of pinus rigida extract.