Bongkrekic acid as a selective activator of the peroxisome proliferator-activated receptor γ (PPARγ) isoform

Abstract

-Bongkrekic acid (BKA), an antibiotic isolated from Pseudomonas cocovenans, is an inhibitory molecule of adenine nucleotide translocase. Since this translocase is a core component of the mitochondrial permeability transition pore (MPTP) formed by apoptotic stimuli, BKA has been used as a tool to abrogate apoptosis. However, the other biochemical properties of BKA have not yet been resolved. Although the definition of a fatty acid is a carboxylic acid (-COOH) with a long hydrocarbon chain (tail), when focused on the chemical structure of BKA, the molecule was revealed to be a branched unsaturated tricarboxylic acid that resembled the structure of polyunsaturated fatty acids (PUFAs). Peroxisome proliferator-activated receptors (PPARs) consist of a subfamily of three isoforms: α, β, and γ, the ligands of which include PUFAs. Using completely synthesized BKA together with simplified BKA derivatives (purity: > 98%), we herein demonstrated the utility of BKA as a selective activator of the human PPARγ isoform, which may not be associated with the anti-apoptotic nature of BKA. We also discussed the possible usefulness of BKA.

Cannabidiolic acid dampens the expression of cyclooxygenase-2 in MDA-MB-231 breast cancer cells: Possible implication of the peroxisome proliferator-activated receptor β/δ abrogation

“…The following primers were used: COX-2 (sense), 5'-CCG-GGTACAATCGCACTTAT-3'; COX-2 (antisense), 5'-GGCGCTCAGCCATACAG-3'; FA2H (sense), 5'-AACGAGCCTGTAGCCCTTGA-3'; FA2H (antisense), 5'-ACTGCCACCGTGTACTCTGTT-3'; adiponectin (sense), 5'-GGTCTCGAACTCCTGGCCTA-3'; adiponectin (antisense), 5'-TGAGATATCGACT-GGGCATGGT-3'; β-actin (sense), 5'-GGCCACGGCT-GCTTC-3'; β-actin (antisense), 5'-GTTGGCGTACAG-GTCTTTGC-3'. The primers for β-actin, COX-2, FA2H, and adiponectin were previously described (Takeda et al, 2013(Takeda et al, , 2014bRoelofs et al, 2014;Okazaki et al, 2015). COX-2, FA2H, and adiponectin mRNA levels were normalized to β-actin.…”

A Novel Bongkrekic Acid Analog-Mediated Modulation of the Size of Lipid Droplets: Evidence for the Appearance of Smaller Adipocytes

“…20) Therefore, we initially examined whether BKA (25 µM) (Fig. 1) activates PPAR transcriptional activity in 3T3-L1 preadipocyte cells.…”

“…19) We also reported that chemically synthesized BKA promoted PPARγ transcriptional activity in MCF-7 breast cancer cells. 20) We herein investigated whether BKA, together with its analogs newly synthesized in this study ( Fig. 1), stimulates PPARγ in pre-adipocyte 3T3-L1 cells.…”

HU-210, a synthetic analog of ∆⁹-THC, is not a modifier of estrogen signaling in MCF-7 human breast cancer cells

“…All other reagents were of analytical grade, commercially available, and used without further purification. Cell culture conditions and methods were performed basically as described previously (Takeda et al, 2013;Okazaki et al, 2015). In brief, the human breast cancer cell line, MCF-7 (obtained from the American Type Culture Collection, Rockville, MD, USA), was routinely grown in phenol red-containing minimum essential medium α (Invitrogen, Carlsbad, CA, USA), supplemented with 10 mM HEPES [4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid], 5% fetal bovine serum, 100 U/mL of penicillin, and 100 μg/mL of streptomycin in a humidified incubator, within an atmosphere of 5% CO 2 at 37°C.…”