Caffeic Acid, an Active Ingredient in Coffee, Combines with DOX for Multitarget Combination Therapy of Lung Cancer

Abstract

Adjuvant diet therapy is an important means of comprehensive treatment of cancer. It is recognized by patients for its high safety, painlessness, and ease to operate. However, the development of adjuvant dietary therapy is limited by unclear targets and unclear anticancer mechanisms. In this work, caffeic acid was found as an inhibitor of TMEM16A with an IC 50 of 29.47 ± 3.19 μM by fluorescence quenching and whole-cell patch-clamp experiments. Caffeic acid regulated the proliferation, migration, and apoptosis of lung cancer cells targeting TMEM16A, which was detected by CCK-8, colony formation, wound healing, and Annexin V assays. In addition, molecular docking combined with site-directed mutagenesis confirmed that the binding sites of caffeic acid to TMEM16A were D439, E448, and R753. Western blot results indicated that caffeic acid regulated the growth of lung cancer through the MAPK pathway. In vitro experiments showed that the inhibitory effect of caffeic acid combined with hydroxydaunorubicin (DOX) on lung cancer cell growth was better than a double concentration of any single dose. In vivo pharmacokinetic experiments and tumor xenograft experiments indicated that the combination of 5.4 mg/kg caffeic acid and 4.1 mg/kg DOX achieved 85.6% tumor suppression rate and offset the side effects. Therefore, caffeic acid is a safe and efficient antitumor active ingredient of food that can enhance the antitumor effect of DOX.

Skin cancer: understanding the journey of transformation from conventional to advanced treatment approaches

“…It can be derived from almost all plants, especially coffee, thyme, and olive plants. The properties such as antitumor, antioxidative, and anti-inflammatory make this compound a potential option for diseases which are induced by any kind of exogenous and endogenous stress [ 339 ]. The antioxidant role protects cells from oxidative damage caused by reactive oxygen species (ROS).…”

“…The findings demonstrated that the inhibitory effects were better with the less dose of two drugs as compared to double dose of single drug. In this study, CA was augmenting the effects of DOX by inhibiting proliferation, migration, and inducing apoptosis [ 339 ]. Such various evidence validates the application of CA in downregulating molecular pathways which are responsible for the initiation of inflammatory conditions which leads to the development of precancerous lesions.…”

Natural Compound Allicin Containing Thiosulfinate Moieties as Transmembrane Protein 16A (TMEM16A) Ion Channel Inhibitor for Food Adjuvant Therapy of Lung Cancer

“…30 It has been found that ingredients in various functional foods showed anticancer activity, such as broccoli, 31 ginger, 32 and coffee. 33 The main elements limiting their application include the high effective concentration of these ingredients and the low content in food so making it difficult to produce an anticancer effect by only dietary sources. 34 In addition, the extraction processes of some components are complex and have low druggability, so they cannot be produced on a large scale.…”

“…Food adjuvant therapy is becoming popular in cancer treatment because it enhances treatment effects and reduces side effects . It has been found that ingredients in various functional foods showed anticancer activity, such as broccoli, ginger, and coffee . The main elements limiting their application include the high effective concentration of these ingredients and the low content in food so making it difficult to produce an anticancer effect by only dietary sources .…”

High Added-Value by-Products from Biomass: A Case Study Unveiling Opportunities for Strengthening the Agroindustry Value Chain

“…Caffeic acid, a metabolite derived from chlorogenic acid, is also described in the literature as a phenolic compound found in coffee's silver skin (Figure 5). Despite possessing a lower commercial value compared to CQAs (1 g of caffeic acid equivalent to $50), it boasts a wide range of biological activities, including antioxidant, antiviral, anticancer, antiplasmodial, and antidiabetic properties [93][94][95].…”