Chemoprevention of cancer: protease inhibitors

G, Hocman

doi:10.1016/0020-711x(92)90061-5

Cited by 21 publications

(6 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The known Gac seed trypsin inhibitors have a low molecular weight of 3–4 kDa with a compact cyclic conformation [ 6 , 21 ], which can make it easy for them to penetrate into cancer cells and illicit cytotoxicity [ 43 ]. However, this is also consistent with the known anticancer potential of bigger proteins from Gac aril (35 kDa) [ 17 ] and other seeds, such as soybeans [ 44 ], which has been studied extensively [ 26 , 45 , 46 , 47 ].…”

Section: Discussionsupporting

confidence: 81%

“…Furthermore, karounidiol, a triterpenoid compound, likely a saponin, present in Gac seeds [ 19 ], possess cytotoxic activity against human cancer cell lines [ 20 ]. Protease inhibitors, like the trypsin inhibitors in Gac seeds [ 7 , 8 , 21 ], have diverse biochemical functions [ 4 , 22 ], including acting as anticancer agents by inhibiting the growth of transformed cells [ 23 , 24 , 25 , 26 ]. Some trypsin inhibitors, such as those from Cajanus cajan and Phaseolus limensis , possess antioxidant, anti-inflammatory, and anti-bacterial activity [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Bioactive Composition, Antioxidant Activity, and Anticancer Potential of Freeze-Dried Extracts from Defatted Gac (Momordica cochinchinensis Spreng) Seeds

Huynh

Parks

et al. 2018

Medicines

View full text Add to dashboard Cite

Background: Gac (Momordica cochinchinensis Spreng) seeds have long been used in traditional medicine as a remedy for numerous conditions due to a range of bioactive compounds. This study investigated the solvent extraction of compounds that could be responsible for antioxidant activity and anticancer potential. Methods: Defatted Gac seed kernel powder was extracted with different solvents: 100% water, 50% methanol:water, 70% ethanol:water, water saturated butanol, 100% methanol, and 100% ethanol. Trypsin inhibitors, saponins, phenolics, and antioxidant activity using the 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and the ferric reducing antioxidant power (FRAP) assays; and anticancer potential against two melanoma cancer cell lines (MM418C1 and D24) were analysed to determine the best extraction solvents. Results: Water was best for extracting trypsin inhibitors (581.4 ± 18.5 mg trypsin/mg) and reducing the viability of MM418C1 and D24 melanoma cells (75.5 ± 1.3 and 66.9 ± 2.2%, respectively); the anticancer potential against the MM418C1 cells was highly correlated with trypsin inhibitors (r = 0.92, p < 0.05), but there was no correlation between anticancer potential and antioxidant activity. The water saturated butanol had the highest saponins (71.8 ± 4.31 mg aescin equivalents/g), phenolic compounds (20.4 ± 0.86 mg gallic acid equivalents/g), and antioxidant activity, but these measures were not related to anticancer potential. Conclusions: Water yielded a Gac seed extract, rich in trypsin inhibitors, which had high anticancer potential against two melanoma cell lines.

show abstract

Section: Discussionsupporting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Bioactive Composition, Antioxidant Activity, and Anticancer Potential of Freeze-Dried Extracts from Defatted Gac (Momordica cochinchinensis Spreng) Seeds

Huynh

Parks

et al. 2018

Medicines

View full text Add to dashboard Cite

show abstract

“… 28 On this basis, protease inhibitors have been proposed as a potential new therapeutic tool in chemotherapy of cancer 29 ,. 30 Our findings in PTC seems to suggest the hypothesis that the absence of A1ACT and A1AT could be associated with a poor prognosis. In the two cases of papillary carcinomas which resulted negative for A1ACT and for A1AT, we observed some peculiar clinicopathological findings: in case 8, the histological picture was characterized by signs of local aggressiveness (diffuse infiltration of the capsule and large areas of necrosis); in case 3, the clinical history was characterized by the early development of the neoplasm (15 years), by a rapid onset of lymph node metastases and by a recurrence of the neoplasm within 6 months after surgery.…”

Section: Discussionsupporting

confidence: 54%

Alpha‐1‐antichymotrypsin immunoreactivity in papillary carcinoma of the thyroid gland

Lai

Rizzo

et al. 1998

Histopathology

View full text Add to dashboard Cite

Our preliminary study shows that A1ACT is expressed by tumour cells in a large proportion of papillary carcinomas of the thyroid gland. Its significance remains, to the best of our knowledge, still unknown. The observation of a more aggressive behaviour in the two cases characterized by the absence of immunoreactivity for both A1ACT and A1AT suggests that the presence or absence of protease inhibitors could play a role in controlling tumour progression in PTC.

show abstract

“…One of the most significant biological application of PIs is their capacity to be used as anti-cancer agents by arresting the growth of transformed cells [4–8]. PIs from plant sources have acquired exceptional imporatnce as natural plant protecting agents [9].…”

Section: Introductionmentioning

confidence: 99%

Allium sativum Protease Inhibitor: A Novel Kunitz Trypsin Inhibitor from Garlic Is a New Comrade of the Serpin Family

et al. 2016

View full text Add to dashboard Cite

PurposeThis study was aimed to purify and characterize the Protease inhibitor (PI) from a plant Allium sativum (garlic) with strong medicinal properties and to explore its phytodrug potentials.MethodsAllium sativum Protease Inhibitor (ASPI) was purified using ammonium sulphate fractionation and Fast Protein Liquid Chromatography on anion exchanger Hi-Trap DEAE column. The purified protein was analyzed for its purity and molecular weight by SDS PAGE. The confirmation of presence of trypsin inhibiting PI was performed by MALDI TOF-TOF and analyzed by MASCOT database. The ASPI was further investigated for its kinetic properties and stability under extreme conditions of pH, temperature and chemical denaturants. Secondary structure was determined by Circular Dichorism (CD) spectroscopy.ResultsASPI of ~15 kDa inhibited trypsin and matched "truncated kunitz Trypsin Inhibitor (Glycine max)" in MASCOT database. The purified ASPI showed 30376.1371 U/mg specific activity with a fold purity of 159.92 and yield ~93%. ASPI was quite stable in the range of pH 2–12 showing a decline in the activity around pH 4–5 suggesting that the pI value of the protein as ASPI aggregates in this range. ASPI showed stability to a broad range of temperature (10–80°C) but declined beyond 80°C. Further, detergents, oxidizing agents and reducing agents demonstrated change in ASPI activity under varying concentrations. The kinetic analysis revealed sigmoidal relationship of velocity with substrate concentration with Vmax 240.8 (μM/min) and Km value of 0.12 μM. ASPI showed uncompetitive inhibition with a Ki of 0.08±0.01 nM). The Far UV CD depicted 2.0% α -helices and 51% β -sheets at native pH.ConclusionsTo conclude, purified ~15 kDa ASPI exhibited fair stability in wide range of pH and temperature Overall, there was an increase in purification fold with remarkable yield. Chemical modification studies suggested the presence of lysine and tryptophan residues as lead amino acids present in the reactive sites. Therefore, ASPI with trypsin inhibitory property has the potential to be used as a non-cytotoxic clinical agents.

show abstract

Chemoprevention of cancer: protease inhibitors

Cited by 21 publications

References 34 publications

Bioactive Composition, Antioxidant Activity, and Anticancer Potential of Freeze-Dried Extracts from Defatted Gac (Momordica cochinchinensis Spreng) Seeds

Bioactive Composition, Antioxidant Activity, and Anticancer Potential of Freeze-Dried Extracts from Defatted Gac (Momordica cochinchinensis Spreng) Seeds

Alpha‐1‐antichymotrypsin immunoreactivity in papillary carcinoma of the thyroid gland

Allium sativum Protease Inhibitor: A Novel Kunitz Trypsin Inhibitor from Garlic Is a New Comrade of the Serpin Family

Contact Info

Product

Resources

About