Chlorogenic acid induces apoptosis, inhibits metastasis and improves antitumor immunity in breast cancer via the NF‑κB signaling pathway

Abstract

Breast cancer which is the most common type of diagnosed cancer among women worldwide possesses metastatic potential, multi-drug resistance, and high mortality. The NF-κB signaling pathway has been revealed to be abnormally activated in breast cancer cells and closely associated with high metastasis and poor prognosis. In the present study, it was reported that chlorogenic acid (CGA), a potent NF-κB inhibitor derived from coffee, exerted antitumor activity in breast cancer. MTT and colony formation assays were conducted and it was revealed that CGA inhibited viability and proliferation in breast cancer cells. Additionally, CGA significantly induced apoptosis and suppressed migration and invasion in breast cancer cells. Notably, immunofluorescence analysis confirmed that CGA could efficiently suppress nuclear transcription of NF-κB p65. In addition, results of western blotting demonstrated that CGA markedly impaired the NF-κB and EMT signaling pathways. The antitumor effect of CGA was evaluated in a subcutaneous tumor mouse model of 4T1 cells, and the results revealed that CGA markedly retarded tumor growth and prolonged the survival rate of tumor-bearing mice. Notably, CGA inhibited pulmonary metastasis of 4T1 cells by enhancing the proportion of CD4 + and CD8 + T cells in spleens of mice, which indicated an improvement of antitumor immunity. In conclusion, the present present study demonstrated that CGA improved antitumor immunity, exerting antitumor and anti-metastatic effects by impairing the NF-κB/EMT signaling pathway, suggesting that CGA may serve as a potential candidate for therapy of breast cancer.

Influences of Microwave-Assisted Extraction Parameters on Antioxidant Activity of the Extract from Akebia trifoliata Peels

“…These compounds might partly contribute to the antioxidant activity of Akebia trifoliate peel extract. Chlorogenic acid was one of the most abundant polyphenols in many natural products and exhibited antioxidant, anti-inflammatory as well as anticancer effects (such as anti-metastatic effects and anti-proliferative activity) [ 26 , 27 , 28 , 29 ]. Besides, clinical studies indicated that chlorogenic acid could decrease the risk of metabolic syndromes and chronic diseases (cardiovascular diseases, neurodegenerative diseases and liver diseases).…”

Chlorogenic Acid Enhances Doxorubicin-Mediated Cytotoxic Effect in Osteosarcoma Cells

“…The ability to induce apoptosis has intensely been debated as one of the possible mechanisms by which CGA exerts its antitumor effect in preclinical cancer models, including in OS [21,23,24,36,37]. Specifically, the intrinsic pathway is actively involved in CGA-mediated apoptosis occurrence [21,24,36].…”

“…Moreover, even though an initial CGA Phase I clinical trial has recently been concluded, demonstrating that its injection is safe and well-tolerated in recurrent high grade glioma patients, collecting safety data in a larger statistical sample is absolutely necessary to define the tolerance and pharmacokinetics of this compound (NCT02245204). Limited studies have been conducted even in preclinical models, and thus additional insights must be provided aimed at defining the CGA impact on both cancer and healthy tissues [37,57]. In this respect, we previously addressed the colony-forming ability in both OS and non-tumor mouse embryonic fibroblasts NIH 3T3 [23].…”

“…Depending on the dosage applied, Doxo can destroy tumor cells through multiple death mechanisms, including mitotic catastrophe and programmed cell death [35]. Similarly, in most cancer studies in which CGA exhibits cytotoxic properties, apoptosis constitutes one of the main signalings involved in [21,[36][37][38].…”

Combination immunotherapy of chlorogenic acid liposomes modified with sialic acid and PD-1 blockers effectively enhances the anti-tumor immune response and therapeutic effects

“…Chlorogenic acid (CA) is a polyphenolic compound that exerts biological activities including antibacterial and anticancer activity (Zeng et al, 2021 ). CA has a significant inhibitory effect on liver cancer, lung cancer, glioma, and other tumors and is considered to be an effective anti-cancer agent (Huang et al, 2019 ).…”