Co-treatment of THP-1 cells with naringenin and curcumin induces cell cycle arrest and apoptosis via numerous pathways.

Abstract

Acute myeloid leukemia (AML) is a hematological malignancy with a low survival rate. Curcumin, which is a multi-targeted anticancer agent, has been shown to exert anti‑oxidant, anti‑inflammatory, anti‑mutagenic and anti‑carcinogenic activities. Naringenin is extracted from citrus fruits and exerts anti‑mutagenic and anti‑carcinogenic activities in various types of cancer cells. However, the effects of curcumin and naringenin in combination in AML cells have yet to be studied. The present study aimed to investigate the combination effects of curcumin and naringenin on the viability, cell cycle distribution and apoptosis rate of THP‑1 cells using cell viability assays, flow cytometry, and western blotting. Naringenin enhanced curcumin‑induced apoptosis and cell viability inhibition. In addition, curcumin and naringenin induced cell cycle arrest at S phase and G2/M phase. Numerous pathways, including p53, c‑Jun N‑terminal kinases (JNK), Akt and extracellular signal‑regulated kinases (ERK)1/2 pathways were markedly altered following treatment of THP‑1 cells with curcumin and naringenin. These results indicated that naringenin may enhance curcumin‑induced apoptosis through inhibiting the Akt and ERK pathways, and promoting the JNK and p53 pathways.

• Authors: Dunyun Shi, Yun Xu, Xin Du, Xuhong Chen, Xiaoli Zhang, Jin Lou, Ming Li, Jiacai Zhuo
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 12 Issue 6 Pg. 8223-8 (Dec 2015) ISSN: 1791-3004 [Electronic] Greece
• PMID: 26496980 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Flavanones
• Tumor Suppressor Protein p53
• Proto-Oncogene Proteins c-akt
• Extracellular Signal-Regulated MAP Kinases
• MAP Kinase Kinase 4
• naringenin
• Curcumin

Topics

• Antineoplastic Agents (pharmacology)
• Antineoplastic Combined Chemotherapy Protocols (pharmacology)
• Apoptosis (drug effects)
• Cell Cycle Checkpoints (drug effects)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Curcumin (pharmacology)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Flavanones (pharmacology)
• Humans
• Leukemia, Myeloid, Acute (pathology)
• MAP Kinase Kinase 4 (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Signal Transduction (drug effects)
• Tumor Suppressor Protein p53 (metabolism)