Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P21554 (
cannabinoid receptor
)
3,582
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Nonsteroidal anti-inflammatory drug (NSAID)-activated gene-1 (
NAG-1
) has received greater attention as a novel molecular target for anti-cancer therapeutics in recent years. We identified a novel synthetic hexahydrocannabinol analog, LYR-8 [(1-((9S)-1-hydroxy-6,6,9-trimethyl-6a,7,8,9,10,10a-hexahydro-6H-benzo[c]chromen-2-yl)ethanone)], as a potent
NAG-1
and apoptosis inducer in a panel of human cancer cells. LYR-8 did not possess any affinity for
cannabinoid receptor
CB(1) or CB(2), which eliminates the concern about potential psychoactive side effects. LYR-8 dramatically induced
NAG-1
expression and apoptosis in HCT116 (wild-type p53) and HT29 (mutant p53) colon cancer cells. The
NAG-1
expression by LYR-8 was not blocked by pifithrin-alpha, a specific p53 inhibitor, which was different from doxorubicin that induced p53-dependent
NAG-1
transcriptional activity. The induction of
NAG-1
promoter activity by LYR-8 was strongly correlated with increased Sp1 activation as noted in various luc-promoter activities. Furthermore, pretreatment with the specific Sp1 inhibitor mithramycin A completely reversed the LYR-8-induced
NAG-1
expression in both HCT116 and HT29 cells. Knockdown of
NAG-1
using siRNA significantly reversed LYR-8-induced cell death in both wild-type and mutant p53-expressing colon cancer cells. Furthermore, sensitization with
NAG-1
inducer sulindac sulfide synergized LYR-8-induced cell death in both colon cancer cells. These results suggest that induction of
NAG-1
via Sp1 activation is a promising therapeutic approach in cancer treatment, and that a novel compound like LYR-8 could be a potent chemotherapeutic agent for colon cancers including p53-mutated cancer.
...
PMID:Induction of p53-independent apoptosis by a novel synthetic hexahydrocannabinol analog is mediated via Sp1-dependent NSAID-activated gene-1 in colon cancer cells. 2023 Jul 99
