Protective Effect of Caffeic Acid on Paclitaxel Induced Anti-Proliferation and Apoptosis of Lung Cancer Cells Involves NF-κB Pathway

Abstract

Caffeic acid (CA), a natural phenolic compound, is abundant in medicinal plants. CA possesses multiple biological effects such as anti-bacterial and anti-cancer growth. CA was also reported to induce fore stomach and kidney tumors in a mouse model. Here we used two human lung cancer cell lines, A549 and H1299, to clarify the role of CA in cancer cell proliferation. The growth assay showed that CA moderately promoted the proliferation of the lung cancer cells. Furthermore, pre-treatment of CA rescues the proliferation inhibition induced by a sub-IC50 dose of paclitaxel (PTX), an anticancer drug. Western blot showed that CA up-regulated the pro-survival proteins survivin and Bcl-2, the down-stream targets of NF-κB. This is consistent with the observation that CA induced nuclear translocation of NF-κB p65. Our study suggested that the pro-survival effect of CA on PTX-treated lung cancer cells is mediated through a NF-κB signaling pathway. This may provide mechanistic insights into the chemoresistance of cancer calls.

Synergistic Anticancer Activity of Combined Use of Caffeic Acid with Paclitaxel Enhances Apoptosis of Non-Small-Cell Lung Cancer H1299 Cells in Vivo and in Vitro

“…CA also exhibits an anti-cancer effect against human cervical carcinoma, head and neck squamous carcinoma, colon cancer, and renal carcinoma [12][13][14]26]. A previous study showed that CA promoted NSCLC A549 cell proliferation and enhanced PTX-induced proliferation inA549 cells [17], suggesting that it has the potential to facilitate A549 growth through the p53 pathway and enhance the protective effect of PTX. However, the in vivo and in vitro effects on p53 deficiency cell line H1299 and the molecular mechanisms remain unclear.…”

“…To determine the potential therapeutic efficacy and underlying mechanisms of CA in combination with PTX for the treatment of NSCLC, we used both H1299 cells and a xenograft mouse model in this study because a previous study had shown the protective effect of CA on PTX-induced cell death in NSCLC A549 cells through the NF-κB signaling pathway [17]. It was found in the previous study that high-dose CA (600 μM) significantly induces apoptosis in A549 and H1299 cells and plays a potential role in modulating and enhancing PTX-induced apoptosis of NSCLC cells both in vivo and in vitro through the MAPK pathway.…”

Therapeutic modulators of STAT signalling for human diseases

“…Caffeic acid, a natural phenolic acid compound present in fruits, wine and coffee 100 , and its synthetic derivative, CAPDE, were reported to inhibit tumour growth and angiogenesis in a renal carcinoma mouse xenograft model. Its effects are induced partly by suppressing active STAT3 and the expression of hypoxia-inducible factor 1α (HIF1α) and VEGF 101 .…”

A new lignan glycoside and phenolics from the branch wood of Pinus banksiana Lambert

“…Caffeic acid ( II ) showed multiple biological effects such as antidiabetic, antibacterial, antitumor, antioxidant, neuroprotective, anti-inflammatory, and antimicrobial, and it inhibited α -glucosidase (Kumar et al 2012 ;Lin et al 2012 ;Singh et al 2012 ). Cedrusin ( III ) could significantly promote the growth of Lactarius deliciosus (Gong 2008 ).…”