Nimbolide, a neem limonoid abrogates canonical NF-κB and Wnt signaling to induce caspase-dependent apoptosis in human hepatocarcinoma (HepG2) cells.
Nuclear factor kappa B (NF-κB), an oncogenic signaling factor plays a critical role in the development and progression of various cancers. The objective of this study was to investigate the effect of nimbolide, a neem derived tetranortriterpenoid on NF-κB signaling and its downstream events - Wnt/β-catenin activation and apoptosis evasion in human hepatocarcinoma (HepG2) cells by evaluating NF-κB family members (NF-κB-p50, p65, IκB-α, p-IκB-α, and IKKβ), members of Wnt signaling (GSK-3β and β-catenin), and intrinsic apoptosis (Bcl-2, Bax, cytochrome c, Smac/DIABLO, caspase-3, and caspase-9). Our results demonstrate that nimbolide concurrently abrogates canonical NF-κB and Wnt signaling and induces intrinsic apoptosis in HepG2 cells. These data suggest that phytochemicals such as nimbolide that can target multiple steps along the NF-κB signaling circuit are promising candidates for future phytochemical-based mechanistic pathway targeted anticancer regimens.
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar-608 002, Tamil Nadu, India.
Krishnamurthy
K
Kavitha
Ramamurthi
R
Vidya Priyadarsini
Prabukumar
P
Anitha
Krishnan
K
Ramalingam
Ramasamy
R
Sakthivel
Gempuraj
G
Purushothaman
Abhishek Kumar
AK
Singh
Devarajan
D
Karunagaran
Siddavaram
S
Nagini
D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D056945:Hep G2 Cells; D006801:Humans; D036701:Limonins / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D060449:Wnt Signaling Pathway / Q000187:drug effects*
D036701:Limonins; D016328:NF-kappa B; C042198:nimbolide; D053148:Caspase 3; D053453:Caspase 9