Hydroxytyrosol inhibits cholangiocarcinoma tumor growth: An in vivo and in vitro study

Abstract

Thymidine kinase 1 (TK1) is a pyrimidine metabolic pathway enzyme involved in salvage DNA synthesis and thus, a cell cycle-dependent marker. We have developed anti-TK1 monoclonal/polyclonal Abs raised against a 15-amino acid synthetic peptide (KPGEAVAARKLFAPQ) corresponding to part of the C-terminus of human TK1. These Abs are useful for both serological and immunohistochemical detection of TK1 in a number of cancer diseases. In this study we examined TK1 concentration in serum (STK1) in 250 preoperative non-small cell lung cancer patients (NSCLC), including 188 non-metastatic (group M0) and 62 metastatic patients (group M1). Serum from 16 healthy individuals was used as controls. The concentration of STK1 of preoperative NSCLC patients was significantly higher than STK1 of healthy individuals (p<0.0001). In group M0, preoperative STK1 concentration was significantly higher in patients of tumour size T2, as compared to tumour size T1 (p=0.042), and in T3-T4, as compared to T1-T2 (p=0.01). No significant difference in STK1 concentration between patients of tumour stage I and stage II (p=0.057) were found, but significantly higher STK1 concentration in patients of stage III, as compared stage I-II (p=0.025). No significant difference of STK1 concentration were found in patients of group M1 concerning tumour size or tumour stage, or between patients with adenocarcinomas (AC) and squamous cell carcinomas (SCC). We studied the changes of STK1 concentration individually one month after operation in metastatic subjects (group M1, n=19) and in tumour-free subjects (group M0, n=38). In the M0 group, the concentration of STK1 one month after operation was significantly decline by 45%, when comparing to concentrations of STK1 preoperative (p<0.001). In the group M1, however, no significant decrease in STK1 concentrations were found one month after operation. We conclude that STK1 has prognostic value and is a reliable marker for monitoring the response to surgery of NSCLC patients.

Cytotoxic and Apoptotic Effects of Hydroxytyrosol on Ovarian Cancer Cell Lines: Relationship of Cytotoxic Effect with ERK 1/2 Pathway

“…Hydroxytyrosol is a potential molecule attracting attention with its antioxidant, anti-inflammatory, anti-proliferative and pro-apoptotic effects for treatment of cancer 15 . The cytotoxic and apoptotic effects of HT in breast, colon, colorectal, melanoma, prostate and human promyelocytic leukemia cell lines and the association of these effects with various signal transduction pathways have been shown in former studies 8,10,11,13,16,17 .…”

“…There are studies conducted on different cancer cell lines suggesting that HT may be posing its cytotoxic effect over ERK 1/2 signaling pathway 8,11,17 . It was reported that HT had posed its antiproliferative effect on the human colon carcinoma cell line (HT-29) 8 , (Caco-2) 11 , the cholangiocarcinoma cell lines (KMBC and TFK-1) 17 , the gall bladder cancer cell line (GBC-SD) 17 and the human breast cancer cell line (MCF-7) 21 by inhibiting the phosphorylation of ERK 1/2.…”

Phenolic Compounds Isolated from Olive Oil as Nutraceutical Tools for the Prevention and Management of Cancer and Cardiovascular Diseases

“…Anti-tumor activity of HT has been evidenced by several in vitro studies. In the last five years, it has been reported that treatments with HT exerted anti-proliferative effects on DLD1 human colon cells [71], TFK-1 and KMBC human cholangiocarcinoma cells and GBS-SD human gallbladder cancer cells [72] and hepatocellular carcinoma cells (HepG2, Hep3B, SK-HEP-1 and Huh-7) [73], as well as on breast (MDA and MCF-7), prostate (LNCap and PC3) and colon (SW480 and HCT116) cancer cell lines [74]. However, the magnitude of these anti-proliferative effects have been reported to depend on cell type; one of the studies on prostate cancer cells showed more resistance to growth inhibition respect than breast and colon cancer cells [74].…”

“…However, the magnitude of these anti-proliferative effects have been reported to depend on cell type; one of the studies on prostate cancer cells showed more resistance to growth inhibition respect than breast and colon cancer cells [74]. Anti-tumor effects of HT could also reside in its reported capacity to reduce cell viability and/or promote apoptotic cell death on human cholangiocarcinoma (TFK-1 and KMBC) [72], colon cancer (DLD1) [71], gallbladder cancer (GBS-SD) [72], hepatocellular carcinoma (HepG2, Hep3B, SK-HEP-1 and Huh-7) [73] and papillary (TPC-1, FB-2) and follicular (WRO) thyroid cancer cells [75] (Figure 1, Table 1). …”

“…Anti-proliferative effects have been associated with an arrest of cell cycle in G2/M phase (Figure 1) in TFK-1 and KMBC human cholangiocarcinoma cells, GBS-SD human gallbladder cancer cells [72] and several hepatocellular carcinoma cells (HepG2, Hep3B, SK-HEP-1 and Huh-7) [73], which resulted in cellular apoptosis in many but not all cell types [72]. In relation with these findings, Toteda et al [75] reported a reduction of cyclin D1 expression and an up-regulation of cell cycle key modulator p21 levels in papillary (TPC-1, FB-2) and follicular (WRO) thyroid cancer cell lines, which were associated with a decreased viability and increased apoptosis markers.…”