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Lagerstroemia speciosa (L.) Pers Leaf Extract Attenuates Lung Tumorigenesis via Alleviating Oxidative Stress, Inflammation and Apoptosis.

ABSTRACT: One of the major etiological factors that account for lung cancer is tobacco use. Benzo(a)pyrene [B(a)P], one of the main constituents of tobacco smoke, has a key role in lung carcinogenesis. The present study was conducted to investigate the cytotoxicity of an aqueous ethanolic extract of Lagerstroemia speciosa (L.) Pers leaves (LLE) on human lung adenocarcinoma cells (A549), as well as its in vivo antitumor effect on a lung tumorigenesis mice model. Our results revealed that LLE possesses cytotoxic activity against the A549 cell line. Mice orally administered B(a)P (50 mg/kg body weight) showed an increase in relative lung weight with subsequent decrease in final body weight. Serum levels of tumor marker enzymes AHH, ADA and LDH and the inflammatory mediator NF-?B increased, while total antioxidant capacity (TAC) decreased. In addition, we observed the increased activity of metalloproteinases (MMP-2 and MMP-12) and levels of the tumor angiogenesis marker VEFG and the lipid peroxidation marker MDA, as well as decreased levels of the non-enzymatic antioxidant GSH and enzymatic antioxidants CAT and GSH-Px in lung tissues. Moreover, B(a)P administration up-regulated the expression of the COX-2 gene, pro-inflammatory cytokines TNF-? and IL-6, and an anti-apoptotic gene Bcl-2, and at the same time down-regulated expression of pro-apoptotic genes BAX and caspase-3 and the p53 gene. Pre- and post-treatment with LLE (250 mg/kg body weight) attenuated all these abnormalities. Histopathological observations verified the protective effect of LLE. Overall, the present data positively confirm the potent antitumor effect of L. speciosa leaves against lung tumorigenesis.

SUBMITTER: Mousa AM

PROVIDER: S-EPMC6995620 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Lagerstroemia speciosa (L.) Pers Leaf Extract Attenuates Lung Tumorigenesis via Alleviating Oxidative Stress, Inflammation and Apoptosis.

Mousa Amria M AM El-Sammad Nermin M NM Abdel-Halim Abeer H AH Anwar Nayera N Khalil Wagdy K B WKB Nawwar Mahmoud M Hashim Amani N AN Elsayed Elsayed A EA Hassan Sherien K SK

Biomolecules 20191212 12

One of the major etiological factors that account for lung cancer is tobacco use. Benzo(a)pyrene [B(a)P], one of the main constituents of tobacco smoke, has a key role in lung carcinogenesis. The present study was conducted to investigate the cytotoxicity of an aqueous ethanolic extract of Lagerstroemia speciosa (L.) Pers leaves (LLE) on human lung adenocarcinoma cells (A549), as well as its in vivo antitumor effect on a lung tumorigenesis mice model. Our results revealed that LLE ...[more]

PMID: 31842482

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Project description:Manganese (Mn) is an essential trace element required for the development of human body and acts as an enzyme co-factor or activator for various reactions of metabolism. While essential in trace amounts, excessive Mn exposure can result in toxic accumulations in human brain tissue and resulting extrapyramidal symptoms called manganism similar to idiopathic Parkinson's disease (PD). Quercetin (QCT) has been demonstrated to play an important role in altering the progression of neurodegenerative diseases by protecting against oxidative stress. This study aimed to investigate the protective effect of QCT on Mn-induced neurotoxicity and the underlying mechanism in SK-N-MC human neuroblastoma cell line and Sprague-Dawley (SD) male rat brain. The results showed that Mn treatment significantly decreased the cell viability of SK-N-MC cell and increased the release of lactate dehydrogenase (LDH), which was attenuated by QCT pretreatment at 10 and 20 µg/mL. Compared to the Mn alone group, QCT pretreatment significantly attenuated Mn-induced oxidative stress, mitochondrial dysfunction and apoptosis. Meanwhile, QCT pretreatment markedly downregulated the NF-κB but upregulated the heme oxygenase-1 (HO-1) and Nrf2 proteins, compared to the Mn alone group. Our result showed the beneficial effect of QCT on hematological parameters against Mn in rat brain. QCT decrease reactive oxygen species (ROS) and protein carbonyl levels and increased Cu/Zn-superoxide dismutase (SOD) activity induced in Mn-treated rats. QCT administration caused a significant reduction in the Mn-induced neuroinflammation by inhibiting the expression of inflammatory markers such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). QCT lowered the Mn elevated levels of various downstream apoptotic markers, including Bax, cytochrome c, cleaved caspase-3 and polymerase-1 (PARP-1), while QCT treatment upregulated anti-apoptotic Bcl-2 proteins and prevented Mn-induced neurodegeneration. Furthermore, administration of QCT (25 and 50 mg/kg) to Mn-exposed rats showed improvement of histopathological alteration in comparison to Mn-treated rats. Moreover, administration of QCT to Mn-exposed rats showed significant reduction of 8-hydroxy-2'-deoxyguanosine (8-OHdG), Bax, activated caspase-3 and PARP-1 immunoreactivity. These results indicate that QCT could effectively inhibit Mn induced apoptosis and inflammatory response in SK-N-MC cells and SD rats, which may involve the activation of HO-1/Nrf2 and inhibition of NF-κB pathway.

Dataset Information

Lagerstroemia speciosa (L.) Pers Leaf Extract Attenuates Lung Tumorigenesis via Alleviating Oxidative Stress, Inflammation and Apoptosis.

Publications

<i>Lagerstroemia speciosa</i> (L.) Pers Leaf Extract Attenuates Lung Tumorigenesis via Alleviating Oxidative Stress, Inflammation and Apoptosis.

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