Proteolysis during ripening of reduced fat Cheddar cheeses made with different exopolysaccharide (EPS)-producing and nonproducing cultures was studied. A ropy strain of Lactococcus lactis ssp. cremoris (JFR1) and capsule-forming nonropy and moderately ropy strains of Streptococcus thermophilus were used in making reduced-fat Cheddar cheese. Commercial Cheddar starter was used in making full-fat cheese. Results showed that the actual yield of cheese made with JFR1 was higher than that of all other reduced-fat cheeses. Cheese made with JFR1 contained higher moisture, moisture in the nonfat substance, and residual coagulant activity than all other reduced-fat cheeses. Proteolysis, as determined by PAGE and the level of water-soluble nitrogen, was also higher in cheese made with JFR1 than in all other cheeses. The HPLC analysis showed a significant increase in hydrophobic peptides (causing bitterness) during storage of cheese made with JFR1. Cheese made with the capsule-forming nonropy adjunct of S. thermophilus, which contained lower moisture and moisture in the nonfat substance levels and lower chymosin activity than did cheese made with JFR1, accumulated less hydrophobic peptides. In conclusion, some EPS-producing cultures produced reduced-fat Cheddar cheese with moisture in the nonfat substance similar to that in its full-fat counterpart without the need for modifying the standard cheese-making protocol. Such cultures might accumulate hydrophobic (bitter) peptides if they do not contain the system able to hydrolyze them. For making high quality reduced-fat Cheddar cheese, EPS-producing cultures should be used in conjunction with debittering strains.

Abstract. Foraging patterns of the squash beetle, Epilachna borealis Fabricius (Coleoptera: Coccinellidae), in field cages are not consistent with the hypothesis that this beetle avoids leaves in which its feeding damage has caused the induction of cucurbitacins. E.borealis feeding does not induce accumulation of cucurbitacins inside or outside of feeding trenches. Cucurbitacins do not reduce the survival or growth rate of E. borealis larvae. High concentrations of cucurbitacins fail to deter E.borealis feeding; rather, cucurbitacins are feeding stimulants for squash beetles. Trenching behaviour in E.borealis is facultative and correlates with leaf turgor and the degree to which sticky phloem sap oozes from damaged leaves. Mucilaginous phloem sap in many curcurbit species inhibits feeding by E.borealis when it is applied to beetle mouthparts.

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In this study, we for the first time, investigated the potential anti-cancer effects of a novel analogue of cucurbitacin (Cucurbitacin D) against cervical cancer in vitro and in vivo. Cucurbitacin D inhibited viability and growth of cervical cancer cells (CaSki and SiHa) in a dose-dependent manner. IC50 of Cucurbitacin D was recorded at 400 nM and 250 nM in CaSki and SiHa cells, respectively. Induction of apoptosis was observed in Cucurbitacin D treated cervical cancer cells as measured by enhanced Annexin V staining and cleavage in PARP protein. Cucurbitacin D treatment of cervical cancer cells arrested the cell cycle in G1/S phase, inhibited constitutive expression of E6, Cyclin D1, CDK4, pRb, and Rb and induced the protein levels of p21 and p27. Cucurbitacin D also inhibited phosphorylation of STAT3 at Ser727 and Tyr705 residues as well as its downstream target genes c-Myc, and MMP9. Cucurbitacin D enhanced the expression of tumor suppressor microRNAs (miR-145, miRNA-143, and miRNA34a) in cervical cancer cells. Cucurbitacin D treatment (1 mg/kg body weight) effectively inhibited growth of cervical cancer cells derived orthotopic xenograft tumors in athymic nude mice. These results demonstrate the potential therapeutic efficacy of Cucurbitacin D against cervical cancer.

Ormeloxifene (ORM), is a clinically approved selective estrogen receptor modulator, which has also shown excellent anti-cancer activity, thus it can be an ideal repurposing pharmacophore. Herein, we report therapeutic effects of ORM on prostate cancer (PrCa) and elucidate a novel molecular mechanism of its anti-cancer activity. ORM treatment inhibited epithelial to mesenchymal transition (EMT) process as evident by repression of N-cadherin, Slug, Snail, and vimentin, MMPs (MMP2 and MMP3), β-catenin/TCF-4 transcriptional activity, and induced the expression of pGSK3β. In molecular docking analysis, ORM showed proficient docking with β-catenin and GSK3β. In addition, ORM induced apoptosis, inhibited growth and metastatic potential of PrCa cells and arrested cell cycle in G0-G1 phase via modulation of cell cycle regulatory proteins (inhibition of Mcl-1, cyclin D1, and CDK4 and induction of p21 and p27). In functional assays, ORM remarkably reduced tumorigenic, migratory and invasive potential of PrCa cells. Additionally, ORM treatment significantly (P<0.01) regressed the prostate tumor growth in the xenograft mouse model while administered through intra-peritoneal route (250 μg/mouse; thrice weekly). These molecular effects of ORM were also observed in excised tumor tissues as shown by immunohistochemistry analysis. Our results, for the first time, demonstrate repurposing potential of ORM as an anti-cancer drug for the treatment of advanced stage metastatic PrCa through a novel molecular mechanism involving β-catenin and EMT pathway.