Chemopreventive effects of pterostilbene through p53 and cell cycle in mouse lung of squamous cell carcinoma model

Surien, Omchit; Ghazali, Ahmad Rohi; Masre, Siti Fathiah

doi:10.1038/s41598-021-94508-7

Cited by 12 publications

(11 citation statements)

References 97 publications

(91 reference statements)

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“…The thickness significantly increased from the PM to the M stage as cell proliferation continued to exceed cell apoptosis 32 , 33 . In fact, increased proliferation of bronchial epithelium was observed in NTCU-induced lung SCC in vivo 16 , 18 . Our findings are in line with a study by Surien et al, who found increased epithelium thickness in BALB/c mice after NTCU treatment 15 .…”

Section: Discussionmentioning

confidence: 97%

“…According to a growing number of studies, chemical-induced cancer in animals is the best model for understanding cancer etiology and carcinogenesis as it closely mimics chronic environmental carcinogen exposure 12 . In this regard, N-nitroso-tris-chloroethylurea (NTCU); a component of nitrosoalkylureas, has been shown to induce lung SCC in mice models with a high degree of similarity and comparable histology to human lung SCC 5 , 13 – 16 . According to Wang et al, NTCU can introduce the same sequence of lung SCC lesions seen in humans, namely ‘normal-hyperplasia-metaplasia-dysplasia-SCC’ 5 .…”

Section: Introductionmentioning

confidence: 99%

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NTCU induced pre-malignant and malignant stages of lung squamous cell carcinoma in mice model

Zakaria

Rajab

Chua

et al. 2021

Sci Rep

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Mice have served as an excellent model to understand the etiology of lung cancer for years. However, data regarding dual-stage carcinogenesis of lung squamous cell carcinoma (SCC) remain elusive. Therefore, we aim to develop pre-malignant (PM) and malignant (M) lung SCC in vivo using N-nitroso-tris-chloroethylurea (NTCU). BALB/C mice were allotted into two main groups; PM and M groups which received treatment for 15 and 30 weeks, respectively. Then, the mice in each main group were allotted into three groups; control, vehicle, and cancer (n = 6), which received normal saline, 70% acetone, and 0.04 M NTCU by skin painting, respectively. Histopathologically, we discovered a mix of hyperplasia, metaplasia, and dysplasia lesions in the PM group and intracellular bridge; an SCC feature in the M group. The M group was positive for cytokeratin 5/6 protein which confirmed the lung SCC subtype. We also found significantly higher (P < 0.05) epithelium thickness in the cancer groups as compared to the vehicle and control groups at both the PM and M. Overall, this study discovered that NTCU is capable of developing PM and M lung SCC in mice model at appropriate weeks and the vehicle group was suggested to be adequate as control group for future research.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

NTCU induced pre-malignant and malignant stages of lung squamous cell carcinoma in mice model

Zakaria

Rajab

Chua

et al. 2021

Sci Rep

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“…Other than the induction of cell senescence, p53, also known as the guardian of the genome, is directly engaged in DNA repair processes such as base excision repair (BER) and nucleotide excision repair (NER) [ 61 ]. Moreover, pterostilbene has been shown to up-regulate the p53 protein expression, to exert a chemo-preventive effect against the carcinogenesis of lung squamous cell carcinoma and hepatocellular carcinoma in mouse models [ 62 , 63 ] . In addition to cell senescence and the DNA repair mechanisms of p53 as a tumour suppressor, p53 can also induce apoptosis cell death via receptor-mediated apoptosis and mitochondria-mediated apoptosis [ 64 ].…”

Section: Discussionmentioning

confidence: 99%

Chemopreventive Effects of Oral Pterostilbene in Multistage Carcinogenesis of Skin Squamous Cell Carcinoma Mouse Model Induced by DMBA/TPA

et al. 2022

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Skin squamous cell carcinoma (SCC) is a type of non-melanoma skin cancer. Pterostilbene is a natural compound proven to exhibit various pharmacological properties, including chemo-preventive effects. This study aimed to explore the chemo-preventive effect of oral pterostilbene during initiation, promotion or continuous on multistage skin SCC mouse models induced by 7,12-Dimethylbenz(a)anthracene (DMBA)/12-O-Tetradecanoylphorbol-13-acetate (TPA). The experimental design consists of five groups of female Institute of Cancer Research (ICR) mice, with two control groups of vehicle and cancer. Three oral pterostilbene groups consisted of orally administered pterostilbene during initiation, promotion, or continuously. Oral pterostilbene significantly reduced the number and volume of tumours. Oral pterostilbene demonstrated less severe skin histology changes compared to the cancer control group, with less pleomorphic in the cells and nuclei, and the basement membrane remained intact. Our results showed fewer invasive tumours in oral PT-treated groups than in cancer groups that displayed mitotic bodies, highly pleomorphic cells and nuclei, and basement membrane invasion. The cell proliferation marker (Ki-67) was reduced in oral pterostilbene-treated groups. Overall, oral pterostilbene is a promising chemo-preventive intervention due to its anti-initiation and anti-promotion on skin carcinogenesis. Thus, the potential molecular mechanisms of oral pterostilbene chemo-prevention agent should be explored.

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“…One week later, mice in each group would receive the subcutaneous injection of normal saline or DEX (0.5 mg/kg, 0.1 ml/10 g) every 5 days, and 1 month later, all mice were sacrificed to obtain the tumors to measure the width and length of tumors for calculating the volume using the formula of V = L × W 2 /2, V is the tumor volume, L is the tumor length, and W is the tumor width). Besides, qRT‐PCR was also performed to determine the expression of MALAT1 in tumors, and immunohistochemistry to examine the expression of Ki‐67 and active caspase‐3 according to the previous study 23 …”

Section: Methodsmentioning

confidence: 99%

“…Besides, qRT-PCR was also performed to determine the expression of MALAT1 in tumors, and immunohistochemistry to examine the expression of Ki-67 and active caspase-3 according to the previous study. 23…”

Section: Transwell Assaymentioning

confidence: 99%

Dexmedetomidine inhibits the growth and metastasis of esophageal cancer cells by down‐regulation of lncRNA MALAT1

Zhang

Cai

et al. 2022

The Kaohsiung J of Med Scie

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This study aims to evaluate the effect of dexmedetomidine (DEX)—on esophageal cancer (EC) via regulating long noncoding RNA (lncRNA) metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1). The effect of DEX on MALAT1 expression and EC cell viability was detected. EC cells were divided into Blank, DEX, scrambled/MALAT1 siRNA, and DEX + control/MALAT1 groups, followed by a series of experiments including quantitative reverse‐transcription polymerase chain reaction (qRT‐PCR), western blotting, 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5 diphenyl tetrazolium bromide (MTT), Annexin V‐FITC/PI staining, wound healing, and Transwell assays. Additionally, mice were subjected to the subcutaneous injection of Eca109 cells transfected by control/MALAT1 activation lentiviral vector to construct EC models with the DEX treatment, and then the tumor volume and the expression of Ki‐67 and active caspase‐3 were determined. DEX reduced the expression of MALAT1 in EC cells in a dose‐dependent manner. DEX inhibited the viability of EC cells, but increased the cell apoptosis, which, however, was reversed by MALAT1 overexpression. Moreover, MALAT1 overexpression abolished the inhibitory effect of DEX on the epithelial–mesenchymal transition (EMT) of EC cells, with enhanced migration and invasion. Furthermore, DEX succeeded in decreasing the tumor volume with the down‐regulation of MALAT1. In comparison with the DEX group, mice in the DEX + MALAT1 group had larger tumors, with the up‐regulation of Ki‐67 and the down‐regulation of active caspase‐3. DEX can reduce the expression of MALAT1 in EC cells, thereby inhibiting the proliferation, invasion and migration, as well as EMT, and promoting the apoptosis of EC cells.

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Chemopreventive effects of pterostilbene through p53 and cell cycle in mouse lung of squamous cell carcinoma model

Cited by 12 publications

References 97 publications

NTCU induced pre-malignant and malignant stages of lung squamous cell carcinoma in mice model

NTCU induced pre-malignant and malignant stages of lung squamous cell carcinoma in mice model

Chemopreventive Effects of Oral Pterostilbene in Multistage Carcinogenesis of Skin Squamous Cell Carcinoma Mouse Model Induced by DMBA/TPA

Dexmedetomidine inhibits the growth and metastasis of esophageal cancer cells by down‐regulation of lncRNA MALAT1

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