Abstract Our group has identified a novel long non-coding RNA (lncRNA), SCAL1 (smoke and cancer-associated lncRNA 1), whose expression is associated with smoking and related to cancer malignancy (Thai et al., 2013, AJRCMB). Currently, we have found that SCAL1 expression is necessary in lung epithelial cells during injury in order to initiate repair after exposure to smoke. In lung cancer cells, SCAL1 expression is needed for cancer cells to combat DNA double stranded breaks associated with chemotherapy treatment, especially cisplatin, doxyrubcin, and possibly other DNA damaging reagents. Most interestingly, the induction of SCAL1 expression is regulated by NRF-2. While NRF2 may protect normal cells from injury, it becomes persistently activated in some cancers and may enhance their malignant characteristics. Therefore, SCAL1 expression is an early marker for lung cellular injury and may be involved in lung cancer progression. We believe that smoke-induced SCAL1 expression leads to epithelial repair and enhances cancer cell resistance to chemotherapy. Our hypothesis is that SCAL1 expression in lung cancer is associated with increased malignant potential and is a poor prognostic marker. Citation Format: Sarah Statt, Philip Thai, Ching-Hsien Chen, Ya-Wen Cheng, Steven Belinsky, Reen Wu. Functional roles of SCAL1 expression in lung cancer and progression. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1469. doi:10.1158/1538-7445.AM2014-1469
Abstract This article investigates the mechanistic aspects of NKX2-1 as a tumour suppressor and its oncogenic properties in lung adenocarcinoma. We show that NKX2-1 is a transcriptional factor that directly regulates p53 transcription. In p53 wild-type cells, NKX2-1 interacts with SP1 to down-regulate IKKβ transcription. In p53 mutated cells, NKX2-1 elevates the mutant p53/NF-Y complex to up-regulate IKKβ transcription. NKX2-1-mediated IKKβ expression is responsible for the efficacy of soft agar growth, invasion, and xenograft lung tumour nodule formation. Moreover, tumour aggressiveness attenuated by NKX2-1-mediated IKKβ is predominately through the shuffling of Foxo3a between the cytosol and nucleus of lung cancer cells to modulate E-cadherin expression. A consistent association of NKX2-1 with IKKβ and E-cadherin expression was observed in tumours from lung adenocarcinoma patients. P53 mutated tumours with high NKX2-1 expression have poorer overall survival (OS) and relapse-free survival (RFS) rates than those with low-NKX2-1 expression. Conversely, p53 wild-type tumours with high-NKX2-1 tumours have more favourable OS and RFS rates than those with low-NKX2-1 expression. As such, we demonstrate that aberrant transcription of IKKβ underlines the ability of NKX2-1 to act as a tumour suppressor or to display oncogenic properties in lung adenocarcinoma. Citation Format: Huei Lee, Po-Ming Chen, Tzu-Chin Wu, Yawen Cheng, Chih-Yi Chen. Suppression of lung adenocarcinoma progression by NKX2-1 is dependent on p53 Status. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 778. doi:10.1158/1538-7445.AM2013-778
Bamboo is distributed worldwide, and its different parts are used as foods or as a traditional herb. Recently, antitumoral effects of bamboo extracts on several tumors have been increasingly reported; however, antitumoral activity of bamboo extracts on osteosarcoma remains unclear. In the present study, we investigated effects of an aqueous Phyllostachys edulis leaf extract (PEE) on osteosarcoma cells and the underlying mechanism of inhibition.The growth of human osteosarcoma cell lines 143 B and MG-63 and lung fibroblast MRC-5 cells was determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Apoptosis was demonstrated using TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assay and flow cytometric analysis. Phosphorylation and protein levels were determined by immunoblotting.After treatment with PEE, viability of 143 B and MG-63 cells was dose-dependently reduced to 36.3% ± 1.6% of control values, which were similar to AICAR (5-aminoimidazole-4-carboxamide 1-β-D-ribofuranoside) treatments. In parallel, ratios of apoptotic cells and cells in the sub-G1 phase were significantly increased. Further investigation showed that PEE treatments led to activation of caspase cascades and changes of apoptotic mediators Bcl2, Bax, and p53. Consistently, our results revealed that PEE activated adenosine monophosphate-activated protein kinase (AMPK) signaling, and the AMPK activation was associated with the induction of apoptotic signaling.Our results indicated that PEE suppressed the growth of 143 B and MG-63 cells but moderately affected MRC-5 cells. PEE-induced apoptosis may attribute to AMPK activation and the following activation of apoptotic signaling cascades. These findings revealed that PEE possesses antitumoral activity on human osteosarcoma cells by manipulating AMPK signaling, suggesting that PEE alone or combined with regular antitumor drugs may be beneficial as osteosarcoma treatments.
Cooking oil fumes (COF) exposure was demonstrated to be associated with lung cancer development in Taiwanese nonsmoking women. Previous studies identified Cox-2 overexpression and oxidative DNA damage in lung adenocarcinoma cells after exposure to COF. Involvement of COF in lung tumorigenesis may be associated with cell survival, as well as proliferation of lung adenocarcinoma. To test this hypothesis, A549, a lung adenocarcinoma cell line, was used, and MTT assay data showed that the cell viability of A549 was significantly increased in a concentration-dependent manner by COF treatment for 48 h. Flow cytometery results indicated that the proportion of A549 cell at S-phase was markedly increased after exposure of COF. To elucidate whether the anti-apoptotic c-IAP2 (IAP2) was involved in COF-improved cell survival, IAP2 protein levels was determined by Western blot, and the results showed it was significantly induced by COF in a concentration-dependent manner. Moreover, the suppression of BAY, a nuclear factor (NF)-kappaB binding inhibitor, or the COF-induced IAP2 protein levels indicated that NF-kappaB activation by COF may partly be involved in IAP2 induction. These results showed that the positive impact of COF on cell survival and proliferation of A549 lung tumor cells may be through an induction of IAP2 overexpression.
In Taiwan, colorectal cancer has one of the highest rates of increased incidence in the past two decades. Heterocyclic amines from dietary cooked meats are metabolically activated by NAT2 (N-acetyltransferase 2), which are associated with colorectal cancer incidence. Thus, the NAT2 fast acetylator genotype may be associated with colorectal cancer risk. However, the association between the NAT2 genotype and colorectal cancer risk is not clearly understood. We conducted a study with 244 primary colorectal cancer cases and 299 cancer-free healthy control subjects to verify the association of NAT2 polymorphisms with the risk of Taiwanese colorectal cancer. Our data showed that subjects with the NAT2 W/W homozygous genotype had a 1.63-fold increased risk of colorectal cancer compared with those with the Mx/Mx slow acetylator genotype (95 percent confidence interval, 1.03-2.58); however, no risk was found in the W/Mx heterozygous and Mx/W+W/W fast acetylator genotypes. Being stratified by gender factors, the colorectal cancer risk in females with homozygous W/W or Mx/W+W/W fast acetylators increased 2.47-fold and 2.13-fold compared with those with the Mx/Mx slow acetylator genotype (95 percent confidence interval, 1.27-4.82 for W/W genotype; 95 percent confidence interval, 1.17-3.89 for Mx/W+W/W genotype); however, the risk of the NAT2 genotype and colorectal cancer was not observed in males. Collectively, patients with the NAT2 fast acetylator genotype were more prone to colorectal cancer and reflected the possibility that exposure to heterocyclic amines may contribute to colorectal cancer development in Taiwan, especially in Taiwanese females.
Babesia gibsoni is the predominant tick-borne protozoan blood parasite affecting dogs throughout the Oriental region. Babesia gibsoni is transmitted by Haemaphysalis longicornis, whereas a similar role has been suggested for Rhipicephalus sanguineus. Haemaphysalis longicornis does not occur in Taiwan, but R. sanguineus is widely distributed on dogs. However, clinical cases of babesiosis are mainly restricted to the northern part of the island. The discrepancy between tick distribution and clinical cases stimulated us to investigate the tick species distribution on dogs in northern Taiwan, with the aim to identify the local vector for canine babesiosis.Ticks were collected from stray dogs or free ranging pet dogs in northern Taiwan between 2015 and 2017 and, after identification, were tested for the presence of tick-borne Babesia parasites using PCR and reverse line blot (RLB) hybridisation. Moreover, engorged ticks collected from the dogs were incubated at 28 °C to allow them to oviposit. Their subsequent larval progeny was also examined by PCR/RLB.A total of 1085 ticks collected from 144 stray dogs at different residential areas consisted of 5 different species: H. hystricis (n = 435), R. sanguineus (n = 582), R. haemaphysaloides (n = 43), Amblyomma testudinarium (n = 14) and Ixodes ovatus (n = 11) were identified. Babesia gibsoni DNA was detected in H. hystricis females (10.3%), males (7.0%) and in 2.6% of the nymphs. One R. sanguineus female and one A. testudinarium female tick also carried B. gibsoni DNA. DNA of B. gibsoni was demonstrated in 11 out of 68 (16.2%) batches of larval ticks derived from engorged H. hystricus ticks only. Babesia vogeli DNA was detected only in R. sanguineus females (2.6%) and males (2.4%). DNA of B. vogeli was detected in 13 out of 95 (13.7%) batches of larval ticks derived from engorged R.sanguineus females.Babesia gibsoni DNA was detected in the larval progeny of H. hystricis ticks only, whereas B. vogeli was restricted to the larvae of R. sanguineus. This provides evidence for transovarial passage of B. gibsoni in H. hystricis and evidence that this tick does act as the local vector for this parasite on dogs in northern Taiwan where most cases of babesiosis are reported. The vectorial capacity of R. sanguineus for babesiosis is probably restricted to the transmission of B. vogeli only.
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