• Biomolecules & Therapeutics
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• v.26 no.4
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• pp.409-416
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• 2018

Vasicinone, a quinazoline alkaloid from Adhatoda vasica Nees. is well known for its bronchodilator activity. However its anti-proliferative activities is yet to be elucidated. Here-in we investigated the anti-proliferative effect of vasicinone and its underlying mechanism against A549 lung carcinoma cells. The A549 cells upon treatment with various doses of vasicinone (10, 30, 50, $70{\mu}M$) for 72 h showed significant decrease in cell viability. Vasicinone treatment also showed DNA fragmentation, LDH leakage, and disruption of mitochondrial potential, and lower wound healing ability in A549 cells. The Annexin V/PI staining showed disrupted plasma membrane integrity and permeability of PI in treated cells. Moreover vasicinone treatment also lead to down regulation of Bcl-2, Fas death receptor and up regulation of PARP, BAD and cytochrome c, suggesting the anti-proliferative nature of vasicinone which mediated apoptosis through both Fas death receptors as well as Bcl-2 regulated signaling. Furthermore, our preliminary studies with vasicinone treatment also showed to lower the ROS levels in A549 cells and have potential free radical scavenging (DPPH, Hydroxyl) activity and ferric reducing power in cell free systems. Thus combining all, vasicinone may be used to develop a new therapeutic agent against oxidative stress induced lung cancer.

• Journal of Applied Biological Chemistry
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• v.59 no.2
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• pp.133-136
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• 2016

An acetone extract in the cortex of Ulmus pumila L. was prepared to evaluate its anti-oxidative and anti-proliferative activities. The free radical scavenging activity ($EC_{50}=36.7{\mu}g/mL$) and reducing power ($EC_{50}=53.2{\mu}g/mL$) proportionally increased according to the extract concentration. The acetone extract possessed a potent anti-proliferative activity against human non-small cell lung cancer (A549, $GI_{50}=74.3{\mu}g/mL$) and human colon cancer (SNU-C4, $GI_{50}=92.8{\mu}g/mL$) cells in a dose-dependent manner, but was less effective with human normal cells (L132, human embryonic lung epithelial cell).

• Food Science and Biotechnology
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• v.16 no.6
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• pp.873-878
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• 2007

In this study, we isolated porphyran was isolated from the red seaweed Porphyra yezoensis and assessed in terms of in vitro anti-proliferative activity. Sequential anion-exchange and gel-filtration chromatography led to purification of 3 porphyrans of different molecular masses, which contained <$50\;{\mu}g/mL$ protein and >$10\;{\mu}g/mL$ porphyran. Crude porphyran inhibited cell growth in a dose-dependent manner (0-5 mg/mL). When HT-29 colon cancer cells and AGS gastric cancer cells were cultured with various concentrations of the purified porphyran, cancer cell growth was inhibited by 50% at a low concentration (5 or $10\;{\mu}g/mL$). Furthermore, the polysaccharide portion of the porphyran preparation, rather than the protein portion, is the most effective at inhibiting cancer cell proliferation via apoptosis, as indicated by increased caspase-3 activity. Our results indicate that purified porphyran has significant in vitro anti-proliferative activity (p<0.05).

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.5207-5211
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• 2012

The present study was designed to explore the anti-cell proliferative efficacy of ferulic acid by analysing the expression pattern of cell proliferative markers, proliferating cellular nuclear antigen (PCNA) and cyclin D1, in the buccal mucosa of golden Syrian hamsters treated with 7,12-dimethylbenz(a)anthracene (DMBA). Oral squamous cell carcinomas developed in the buccal pouch of hamsters using topical application of 0.5% DMBA three times a week for 14 weeks. Immunohistochemical (PCNA) and RT-PCR (Cyclin D1) analysis revealed over expression of PCNA and cyclin D1 in the buccal mucosa of hamsters treated with DMBA alone (tumor bearing hamsters). Oral administration of ferulic acid at a dose of 40 mg/kg bw to hamsters treated with DMBA not only completely prevented the tumor formation but also down regulated the expression of PCNA and cyclin D1. The results of the present study thus suggests that ferulic acid might have inhibited tumor formation in the buccal mucosa of hamsters treated with DMBA through its anti-cell proliferative potential as evidenced by decreased expression of PCNA and cyclin D1.

• Journal of Microbiology and Biotechnology
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• v.19 no.11
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• pp.1482-1489
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• 2009

In this study, we investigated the anti-proliferative effect of polysaccharides from Salicornia herbacea on HT-29 human colon cancer cells. Crude polysaccharides from S. herbacea (CS) were prepared by extraction with hot steam water, and fine polysaccharides from S. herbacea (PS) were obtained through further size exclusion chromatography. The anti-proliferative effect of CS and PS were measured using the MTS assay, apoptosis analysis, cell cycle analysis, and RT-PCR. HT-29 cells were treated with CS or PS at different dosages (0.5, 1, 2, 4 mg $ml^{-1}$) for 24 or 48 h. CS and PS inhibited proliferation and stimulated apoptosis of cells in a dose-dependent manner. Flow cytometric analysis after Annexin V-FITC and PI staining revealed that treatment with CS or PS increased total apoptotic death of cells to 24.99% or 91.59%, respectively, in comparison with the control (13.51 %). PS increased early apoptotic death substantially - up to 12 times more than the control. Treatment with CS or PS resulted in a concentration-dependent increase of the G2/M cell population of the cell cycle as determined by flow cytometry. G2/M arrest was induced significantly with the highest concentration (4 mg $ml^{-1}$) of PS. RT-PCR was performed to study the correlation between G2/M arrest and transcription of cell cycle control genes. The anti-proliferative activity of CS and PS was accompanied by inhibition of cyclin B1, and Cdc 2 mRNA. Moreover, both CS and PS induced expression of the p53 tumor suppressor gene and the Cdk inhibitor p21. These results suggest that polysaccharides from S. herbacea have anti-cancer activity in human colon cancer cells.

• International Journal of Oral Biology
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• v.32 no.4
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• pp.135-141
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• 2007

Anti-proliferation of methanol extract of Curcuma rhizome on oral squamous cell carcinoma (KB) and osteosarcoma (HOS) cells were investigated. In order to elucidate the involvement of telomerase inhibitory activity as a part of anti-proliferative effect of Curcuma rhizome on cancer cells, we measured telomerase activity in Curcuma rhizome extract-treated cancer cells. The concentration inhibited cell proliferation to 50% $(IC_{50})$ of the methanol extract of Curcuma rhizome against oral squamous cell carcinoma (KB) cells and osteosarcoma (HOS) cells were 21.30 ${\mu}g/ml$ and 39.3${\mu}g/ml$, respectively. The methanol extract of Curcuma rhizome showed inhibitory telomerase inhibitory effect which is required for cancer cell immortality. Therefore, it seems that the anticancer effect of methanol extract of Curcuma rhizome is at least partially due to telomerase inhibitory effect. Five fraction samples were prepared according to its polarity differences and analyzed anti-proliferative effects of each fraction samples on oral squamous cell carcinoma and osteosarcoma cells. Anticancer effect was observed in dichloromethane, and ethylacetate fractions. The highest anticancer effect was found in dichloromethane fraction which had $IC_{50}$ value of 23.3 ${\mu}g/ml$ and 10.5${\mu}g/ml$ against oral squamous cell carcinoma (KB) cells and osteosarcoma (HOS) cells, respectively.

• Food Science of Animal Resources
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• v.38 no.6
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• pp.1168-1178
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• 2018

The present study aimed to characterise anti-oxidant peptides from water-soluble protein extracts of Hanwoo beef and evaluate their anti-proliferative effect on human colorectal carcinoma cells (HCT116). Antioxidant peptides were purified from the low-molecular-weight fraction (<3 kDa) of Hanwoo beef extract. Antioxidant activity of peptide fractions was determined using the oxygen radical absorbance capacity (ORAC) assay. Purified peptide (P3) displayed higher ORAC activity than the low-molecular-weight fraction ($202.66{\mu}M\;TE/g$ vs $167.38{\mu}M\;TE/g$ of dry matter, respectively) (p<0.05). The peptide sequence of P3 was Cys-Cys-Cys-Cys-Ser-Val-Gln-Lys (888.30 Da). The novel peptide P3, at $250{\mu}g/mL$, also significantly inhibited HCT116 cell proliferation up to 25.24% through phosphorylation of ERK, JNK, and p38 kinase (p<0.05). Hence, antioxidant peptide P3 from Hanwoo beef extract can be used as an antioxidative and anticancer agent in the functional food industry.

• Preventive Nutrition and Food Science
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• v.10 no.2
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• pp.172-178
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• 2005

Dandelions have been reported to have medicinal properties and bioactive components that impact human health. However, the precise biological properties of dandelions and the parts of the plants possessing bioactive components remain uncertain. In this study, we evaluated 3 different types of dandelions based on their cultivation origin (Songpa, Uiryung, and native Uiryung types) as well as their 4 different plant parts (leaf, flower, root, skin). Each sample was extracted with $80\%$ methanol and then compared for the biological activities (anti-oxidative, immune cell proliferative and tumor cell growth inhibitory activities). All 3 types of dandelions possessed a degree of biological functions including the hydroxyl radical scavenger activity, immune cell proliferative activity and tumor cell growth inhibitory activity. However, there was no significant difference in these activities between the 3 dandelion types. Leaves of all three dandelion types showed the highest levels of all biological activities. To a lesser degree, the flower and root parts displayed biological activities. In the skin parts, anti-oxidative activity was also detected only at higher doses of dandelion extracts. Heating the dandelion leaf extract did not affect the biological activity, suggesting a heat-stable nature of the biological compounds. Taken together, these collective data suggest that dandelions, in particular their leaves, possess a high concentration of heat-resistant biological compounds, which are responsible for anti-oxidative, immune cell proliferative and tumor cell growth-inhibitory activities.

• Natural Product Sciences
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• v.12 no.4
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• pp.214-216
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• 2006

Isorhamnetin from the aerial parts of Persicaria thunbergii has been reported to have anti-tumor activity mediated by the inhibition of farnesyl protein transferase. In this study, we investigated the anti-proliferation effects of isorhamnetin on NIH3T3, K-RAS, H-RAS and SW620 cells, and it showed anti-proliferative effects in a dose-dependent manner with $IC_{50}$ value 4.1, 7.9, 20.2, and $22.4{\mu}g/ml$, repectively.

• IMMUNE NETWORK
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• v.15 no.4
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• pp.199-205
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• 2015

T-bet is a critical transcription factor that regulates differentiation of Th1 cells from $CD4^+$ precursor cells. Since T-bet directly binds to the promoter of the IFN-${\gamma}$ gene and activates its transcription, T-bet deficiency impairs IFN-${\gamma}$ production in Th1 cells. Interestingly, T-bet-deficient Th cells also display substantially augmented the production of IL-2, a T cell growth factor. Exogenous expression of T-bet in T-bet deficient Th cells rescued the IFN-${\gamma}$ production and suppressed IL-2 expression. IFN-${\gamma}$ and IL-2 reciprocally regulate Th cell proliferation following TCR stimulation. Therefore, we examined the effect of T-bet on Th cell proliferation and found that T-bet deficiency significantly enhanced Th cell proliferation under non-skewing, Th1-skewing, and Th2-skewing conditions. By using IFN-${\gamma}$-null mice to eliminate the anti-proliferative effect of IFN-${\gamma}$, T-bet deficiency still enhanced Th cell proliferation under both Th1- and Th2-skewing conditions. Since the anti-proliferative activity of T-bet may be influenced by IL-2 suppression in Th cells, we examined whether T-bet modulates IL-2-independent cell proliferation in a non-T cell population. We demonstrated that T-bet expression induced by ecdysone treatment in human embryonic kidney (HEK) cells increased IFN-${\gamma}$ promoter activity in a dose dependent manner, and sustained T-bet expression considerably decreased cell proliferation in HEK cells. Although the molecular mechanisms underlying anti-proliferative activity of T-bet remain to be elucidated, T-bet may directly suppress cell proliferation in an IFN-${\gamma}$- or an IL-2-independent manner.