A PARP1 PROTAC as a novel strategy against PARP inhibitor resistance via promotion of ferroptosis in p53-positive breast cancer.

Therapeutic targeting of the nuclear enzyme poly (ADP-ribose) polymerase 1 (PARP1) with PARP inhibitors (PARPis) in patients with a homologous recombination (HR)- deficient phenotype based on the mechanism of synthetic lethality has been shown tremendous success in cancer therapy. With the clinical use of various PARPis, emerging evidence has shown that some PARPis offer hope for breakthroughs in triple-negative breast cancer (TNBC) therapy, regardless of HR status. However, similar to other conventional cytotoxic drugs, PARPis are also subject to the intractable problem of drug resistance.

The microRNA miR-184 regulates the CYP303A1 transcript level to control molting of Locusta migratoria.

Cytochrome P450 monooxygenases (CYPs) play essential physiological functions in insects. CYP303A1 is highly conserved in insect species studied to date, and shows an indispensable role for adult eclosion in both Locusta migratoria and Drosophila melanogaster. However, how CYP303A1 is regulated to control insect developmental processes remains uninvestigated.

Curcumin derivative C817 inhibits proliferation of imatinib-resistant chronic myeloid leukemia cells with wild-type or mutant Bcr-Abl in vitro.

Aim: To find new kinase inhibitors that overcome the imatinib resistance in treatment of chronic myeloid leukemia (CML), we synthesized C817, a novel derivative of curcumin, and tested its activities against wild-type (WT) and imatinib-resistant mutant Abl kinases, as well as in imatinib-sensitive and resistant CML cells in vitro.

Methods: 32D cells harboring WT or mutant Abl kinases (nucleotide binding P-loop mutants Q252H, Y253F, and imatinib contact residue mutant T315I), as well as K562/G01 cells (with whole Bcr-Abl gene amplication) were tested. Kinase activity was measured using Kinase-Glo Luminescent Kinase Assay Platform in recombinant WT and mutant (Q252H, Y253F, and T315I) Abl kinases.

Metabolic engineering for ethylene production by inserting the ethylene-forming enzyme gene (efe) at the 16S rDNA sites of Pseudomonas putida KT2440.

The ethylene-forming enzyme gene (efe) from Pseudomonas syringae pv. glycinea was transferred into Pseudomonas putida KT2440 by recombination at five of the seven 16S rDNA sites. PCR analysis demonstrated that strains DC1, DC2 and DC3 contained three, four and five copies of efe, respectively.

Human urotensin II in internal mammary and radial arteries of patients undergoing coronary surgery.

Aims: Internal mammary (IMA) and radial artery (RA) have different incidence of vasospasm and long-term patency rates in arterial grafting. We compared the vasoreactivity of human urotensin II (hU-II) and its receptor with mechanism investigations in IMA and RA.

Methods: IMA and RA taken from patients undergoing coronary bypass surgery were studied in organ baths.

Curcumin synergistically augments bcr/abl phosphorothioate antisense oligonucleotides to inhibit growth of chronic myelogenous leukemia cells.

Aim: To investigate the growth inhibition effect of the combination of bcr/abl phosphorothioate antisense oligonucleotides (PS-ASODN) and curcumin (cur), and the possible mechanisms of cur on the chronic myelogenous leukemia cell line K562.

Methods: The K562 cell line was used as a P210( bcr/abl )-positive cell model in vitro and was exposed to different concentrations of PS-ASODN (0-20 micromol/L), cur (0-20 micromol/L), or a combination of both. Growth inhibition and apoptosis of K562 cells were assessed by MTT assay and AO/EB fluorescent staining, respectively.

Down-regulation of p210(bcr/abl) by curcumin involves disrupting molecular chaperone functions of Hsp90.

Aim: To investigate the effects of curcumin (Cur) on p210(bcr/abl) level in K562 cells, and the relationship between these effects and the molecular chaperone functions of heat shock protein 90 (Hsp90).

Methods: Flow cytometry and Western blot were used to examine the abundance of p210(bcr/abl), Hsp90, p23, Hsp70, and p60(Hop) in K562 cells treated with Cur. Reverse transcription polymerase chain reaction (RT-PCR) was used to determine the bcr-abl mRNA level in K562 cells treated with Cur.

Inhibitory effect of curcumin on proliferation of K562 cells involves down-regulation of p210(bcr/abl) initiated Ras signal transduction pathway.

Aim: To investigate the effects of curcumin (Cur) on proliferation of K562 cells and the relationship between these effects and Ras signal transduction pathway activated by p210bcr/abl.

Methods: K562 cell line was used as a p210bcr/abl-positive cell system and HL-60 cell line as a p210bcr/abl-negative control; etoposide (VP-16), which has no influence on p210bcr/abl and has resistance to K562 cells[1], was used as an anticancer drug control to compare with curcumin. MTT was used to determine the proliferative effects of drugs on K562 and HL-60 cells.