chlorogenic-acid and Lung-Neoplasms

The present study shows the chemical profile and cytotoxic properties of the ethanolic extracts of Inula viscosa from Northeast Algeria. The extract was obtained by maceration using ethanol. Its phenolic profile was determined using ultra-high-performance liquid chromatography coupled with a diode array detector and an electrospray mass spectrometer (UHPLC-DAD-ESI/MS), which allowed the identification and quantification of 17 compounds, 1,5-O-caffeoylquinic acid being the most abundant. The cytotoxic activity was assessed against human gastric cancer (AGS) and human non-small-cell lung cancer (A549) cell lines, whereas ethanolic extract elicited nearly 60 % and 40 % viability loss toward AGS and A549 cancer cells, respectively. Results also showed that cell death is caspase-independent and confirmed the involvement of RIPK1 and the necroptosis pathway in the toxicity induced by the I. viscosa extract. In addition, the ethanolic extract would not provoke morphological traits in the cancer cells. These findings suggest that I. viscosa can be a source of new antiproliferative drugs or used in preparation plant-derived pharmaceuticals.

Topics: A549 Cells; Asteraceae; Carcinoma, Non-Small-Cell Lung; Ethanol; Humans; Inula; Lung Neoplasms; Plant Extracts

Lung adenocarcinoma (LAC) is a major worldwide cause of death by cancer, it shows high aggressiveness, functional decline, systemic compromise and severe cachexia, which might be counteracted by dietary redox-active phytochemicals. Therefore, our aim was to establish the anticancer effects of the oral intake of quercetin and 5 caffeoylquinic acid.. LAC-1-bearing male Balb/c mice received quercetin (0-25 μg/kg/d) and 5 caffeoylquinic acid (0-120 μg/kg/d) for three weeks, with different organic and biochemical variables being then compared with ANOVA and the Fisher Test (p <0.05).. Quercetin delayed 1.18 fold tumour appearance and increased 8.87 fold non-neoplastic body weight gain, whereas 5 caffeoylquinic acid did it in a lesser extent (1.17 and 2.48 fold, respectively), with tumour weight being consequent with the evolution time. Quercetin induced >1.15 fold tumour hydroperoxides and lipoperoxides, whereas 5 caffeoylquinic acid induced only lipoperoxides. Although both phytochemicals reduced <0.85 fold hydroperoxides and lipoperoxides in the kidney, only quercetin was also antioxidant in the liver. Additionally, 5 caffeoylquinic acid increased >1.15 fold hepatic and renal weights. Although these phytochemicals did not modify telencephalic interleukin 6 production, quercetin augmented 2.51 fold interleukin 6 in the diencephalon, whereas 5 caffeoylquinic acid decreased it 0.43 fold.. Quercetin delayed lung adenocarcinoma appearance and increased the non-neoplastic body weight gain in mice with tumour oxidative stress, without brain interleukin 6 participation. 5 caffeoylquinic acid showed similar effects, although they were weaker. Additionally, quercetin acted as a hepatic and renal antioxidant, whereas 5 caffeoylquinic acid only exerted this effect in the kidney. Therefore, safe oral doses of this flavonoid are promissory to modulate lung cancer progression, with further studies being encouraged.

Topics: Adenocarcinoma of Lung; Administration, Oral; Animals; Antioxidants; Body Weight; Cachexia; Disease Progression; Interleukin-6; Liver; Lung Neoplasms; Male; Mice; Mice, Inbred BALB C; Oxidation-Reduction; Oxidative Stress; Quercetin; Quinic Acid

In the present study, we investigated the effects and molecular mechanism of 5-caffeoylquinic acid (5-CQA), a natural phenolic compound isolated from Ligularia fischeri, on cell invasion, proliferation and adhesion in p53 wild-type A549 and p53-deficient H1299 non-small cell lung cancer (NSCLC) cells. 5-CQA abrogated mitogen-stimulated invasion, but not proliferation, in both A549 and H1299 cells. In addition, 5-CQA inhibited mitogen-stimulated adhesion in A549 cells only. Anti-invasive activity of 5-CQA in A549 cells was mediated by the inactivation of p70(S6K)-dependent signaling pathway. In contrast, in H1299 cells the inactivation of Akt was found to be involved in 5-CQA-mediated inhibition of cell invasion. Collectively, these findings demonstrate the pharmacological roles and molecular targets of 5-CQA in regulating NSCLC cell fate, and suggest further evaluation and development of 5-CQA as a potential therapeutic agent for the treatment and prevention of lung cancer.

Topics: Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Movement; Cell Proliferation; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms; Neoplasm Invasiveness; Proto-Oncogene Proteins c-akt; Quinic Acid; Ribosomal Protein S6 Kinases, 70-kDa; Signal Transduction; Tumor Suppressor Protein p53