Chlorogenic-induced inhibition of non-small cancer cells occurs through regulation of histone deacetylase 6

Abstract

Chlorogenic acid (CGA), an ester with various pharmacological effects, is important in cancer therapy. However, the specific antitumor mechanism of CGA is not entirely clear, especially with respect to its suppression of non-small cell lung cancer (NSCLC). The present study was carried out to assess the effect of CGA on NSCLC, and the mechanism involved. Cell viability assay and colony formation assay revealed that CGA blocked the proliferative capacity of NSCLC cells in vitro. Results from the migration assay suggested that CGA also inhibited the migration of A549 cells. Other assays further revealed that CGA strongly and selectively inhibited histone deacetylase 6 (HDAC6) activity and suppressed the activity of matrix metalloproteinase-2 (MMP-2) through decreased expression of Ac-NF-κB. Tumorigenicity assay showed that CGA also inhibited the proliferation and metabolism of NSCLC in vivo. These results indicate that CGA significantly suppresses the proliferation of NSCLC by regulating the activity of histone deacetylase 6.

Chlorogenic acid potentiates antitumor effect of doxorubicin through upregulation of death receptors in solid Ehrlich carcinoma model in mice

“…Natural products are an attractive source to identify new compounds for the prevention and treatment of cancer [26]. Previous studies presented that CGA exerts different biological activities such as antitumor activity and chemosensitizing activity [10,[27][28][29]. Therefore, we studied the molecular mechanism of CGA as an effective chemosensitizer that enhances DOX-induced apoptosis in the SEC model in mice.…”

“…CGA has been reported to display a wide spectrum of biological activities such as anticancer [10], antioxidant [11], anti-inflammatory [12] and cardioprotective activities [13]. In addition, CGA acts as an effective chemosensitizing agent leading to suppression of cancer growth depending on its ability to activate and inhibit some important pathways in cancer metabolism [14].…”

Yifei Tongluo, a Chinese Herbal Formula, Suppresses Tumor Growth and Metastasis and Exerts Immunomodulatory Effect in Lewis Lung Carcinoma Mice

“…Angiogenesis, MMPs and EMT play crucial roles in the process of tumor metastasis, which have long been drug targets [ 41 , 42 ]. Chlorogenic acid, major active component of YFTL, significantly suppresses the proliferation of NSCLC and inhibits the activity of MMP-2 [ 23 ]. Additionally, linarin, a major active component of YFTL, inhibited tumor growth and metastasis via down-regulation of Akt and repressed the MMP-9-dependent invasion pathway [ 26 , 27 ].…”

“…The major chemical components of YFTL include coumarins, phenols, flavonoids, alkaloids, and malate esters [ 22 ]. Although YFTL is not traditionally used to treat for lung cancer, some of its active components, such as Chlorogenic acid [ 23 ], Rutin [ 24 , 25 ], linarin [ 26 , 27 ], and esculetin [ 28 , 29 ] have been identified for their effective anti-tumor and anti-metastasis effects in different models. According to the previous reports, the inhibition on tumor growth and metastasis might be associated with the inhibition of cell proliferation and induction of apoptosis, as well as suppression of angiogenesis, alleviation of inflammation responses, up-regulation of E-cadherin and down-regulation of MMP-2 and MMP-9 levels [ 27 , 30 , 31 ].…”

Chlorogenic acid: Potential source of natural drugs for the therapeutics of fibrosis and cancer

“… [124] Human lung cancer A549 cell In-vitro Down-regulates migration of A549 cells, Ac-NF-kB expression, matrix metalloproteinase-2 (MMP-2) and histone deacetylase-6 (HDAC6) activities. [125] 2 Breast cancer Mouse 4T1 breast cancer cell In-vivo Hampers the expression of CD206 triggered by IL-13, M2 related gene Ym1 and metastatic nodes in the lungs. [126] Mouse 4T1 breast cancer cell In-vivo Hinders the viability, proliferation, migration and invasion in breast cancer cells, NF-kB p65 nuclear translocation, EMT and NF-kB mechanism [127] Mouse 4T1, EMT6, BT-549, and MDA-MB-231 cell and EMT6 xenograft model In-vivo and In-vitro Inhibits cell viability, tumor volume and weight, and expressions of EGF, TGF-β, VEGF, CD34, and IL-10; activates apoptosis in a dose dependent manner.…”