The Antitumor Effect of Cinnamaldehyde Derivative CB-PIC in Hepatocellular Carcinoma Cells via Inhibition of Pyruvate and STAT3 Signaling

Autor: Hyungjin Kim, Hyo-Jung Lee, Deok Yong Sim, Ji Eon Park, Chi-Hoon Ahn, Su-Yeon Park, Eungyeong Jang, Bonglee Kim, Sung-Hoon Kim
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: International Journal of Molecular Sciences, Vol 23, Iss 12, p 6461 (2022)
Druh dokumentu: article
ISSN: 1422-0067
1661-6596
DOI: 10.3390/ijms23126461
Popis: Though cinnamaldehyde derivative (CB-PIC), a major compound of cinnamon, is known to have anticancer activity, its underlying mechanism is not fully understood. In the present study, the anticancer mechanism of CB-PIC was investigated in human hepatocellular carcinoma cells (HCCs) in association with signal transducer and activator of transcription 3 (STAT3) signaling. CB-PIC exerted cytotoxicity in HepG2 and Huh7 cells. CB-PIC increased the sub G1 population and attenuated the expression of pro-poly (ADP-ribose) polymerase (PARP) and pro-Caspase3 in HepG2 and Huh7 cells. Interestingly, CB-PIC significantly abrogated the expression of a glycolytic enzyme pyruvate kinase M2 (PKM2) in HepG2 cells more than in LNCaP, A549, and HCT-116 cells. Consistently, CB-PIC reduced the expression of hexokinase 2 (HK2) and PKM2, along with a reduced production of lactate in HepG2 and Huh7 cells. Notably, CB-PIC suppressed the phosphorylation of STAT3 in HepG2 and Huh7 cells and conversely STAT3 depletion enhanced the capacity of CB-PIC to suppress the expression of HK2, PKM2, and pro-caspase3 and to reduce the viability in Huh7 cells. Furthermore, CB-PIC activated the phosphorylation of AMPK and ERK and suppressed expression of IL-6 as STAT3-related genes in HepG2 and Huh7 cells. Conversely, pyruvate treatment reversed the inhibitory effect of CB-PIC on p-STAT3, HK2, PKM2, and pro-PARP in Huh7 cells. Overall, there findings suggest that CB-PIC exerts an apoptotic effect via inhibition of the Warburg effect mediated by p-STAT3 and pyruvate signaling.
Databáze: Directory of Open Access Journals
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