Abstract Title:

Differential mRNA expression in the induction of DNA damage, G/M arrest, and cell death by zerumbone in HepG2/C3A cells.

Abstract Source:

Toxicol In Vitro. 2022 Dec ;85:105474. Epub 2022 Sep 16. PMID: 36122806

Abstract Author(s):

Débora Berbel Lirio Rondina, Luan Vitor Alves de Lima, Matheus Felipe da Silva, Thalita Alves Zanetti, Ingrid Felicidade, Lilian Areal Marques, Giuliana Castello Coatti, Mario Sergio Mantovani

Article Affiliation:

Débora Berbel Lirio Rondina


Zerumbone (ZER) is a phytochemical with antioxidant and antiproliferative properties. This study evaluated the cytoxicity of ZER combined with chemotherapeutic agents and the expression of mRNA genes related to cell cycle, cell death, xenobiotic metabolism, DNA damage, and endoplasmic reticulum (ER) stress in HepG2/C3A cells. ZER was cytotoxic (IC, 44.31 μM). ZER-induced apoptosis was related to BBC3 and ERN1 upregulation (ER stress), and its antiproliferative effects were attributable to MYC, IGF1, and NF-kB mRNA inhibition. ZER-induced G/M arrest and DNA damage was associated with mRNA expression of cell cycle (CDKN1A) and DNA damage (GADD45A) genes. Increased CYP1A2 and CYP2C19 mRNA expression suggested ZER metabolization, and reduced CYP1A1 and CYP2D6 expression indicated a longer time of action of ZER in the cell, enhancing its pharmacological effect. ZER downregulated TP53, PARP1, BIRC5 (apoptosis), and MAP1LC3A (autophagy). In apoptosis assay, the data of the association treatments with ZER suggested antagonism. In cytotoxicity assay, the data of the association treatments with ZER suggested synergism action to cisplatin and antagonism action to doxorubicin and 5-fluorouracil. Thus, ZER has potential for application in chemotherapy as it modulates mRNA targets; however, it may not have the desired efficiency when combined with other chemotherapeutic agents.

Study Type : In Vitro Study

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