Pharmacological manipulation of Ezh2 with salvianolic acid B results in tumor vascular normalization and synergizes with cisplatin and T cell-mediated immunotherapy

Qian, Cheng; Yang, Chunmei; Tang, Yu; Zheng, Weiwei; Zhou, Yueke; Zhang, Shan; Song, Mengyao; Peng, Cheng; Wei, Zhonghong; Zhong, Chongjin; Wan, Li; Wang, Aiyun; Zhao, Yang; Lu, Yin

doi:10.1016/j.phrs.2022.106333

Cited by 31 publications

(14 citation statements)

References 62 publications

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“…The study's results indicate that Sal B-treated NSCLC A549 cells experienced reduced proliferation, migration, and invasion, suggesting that Sal B inhibits NSCLC growth and metastasis. Previous research has shown that Sal B significantly reduces tumour volume and improves overall survival of solid tumour cells by decreasing levels of the oxidative stress marker malondialdehyde and increasing plasma levels of the antioxidant marker glutathione (GSH) [24]. Thus, we have concluded that Sal B's antioxidant activity regulates ROS levels and alters oxidative stress in the tumour microenvironment, leading to the inhibition of A549 cell proliferation and metastasis.…”

Section: Discussionmentioning

confidence: 85%

Salvianolic acid B inhibits the growth and metastasis of A549 lung cancer cells through the NDRG2/PTEN pathway by inducing oxidative stress

Yang,

Huang,

Gao

et al. 2024

Preprint

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Salvianolic acid B (Sal B) has demonstrated anticancer activity against various types of cancer. However, the underlying mechanism of Sal B-mediated anticancer effects remains incompletely understood. This study aims to investigate the impact of Sal B on the growth and metastasis of human A549 lung cells, as well as elucidate its potential mechanisms. In this study, different concentrations of Sal B were administered to A549 cells. The effects on migration and invasion abilities were assessed using MTT, wound healing, and transwell assays. Flow cytometry analysis was employed to evaluate Sal B-induced apoptosis in A549 cells. Western blotting and immunohistochemistry were conducted to measure the expression levels of cleaved caspase 3 (an apoptosis marker) and E-cadherin (a metastasis marker). Commercial kits were utilized for detecting intracellular reactive oxygen species (ROS) and NAD+. Additionally, a xenograft model with transplanted A549 tumors was employed to assess the antitumor effect of Sal B in vivo. The expression levels of NDRG2, p-PTEN, and p-AKT were determined through western blotting. Our findings demonstrate that Sal B effectively inhibits proliferation, migration, and invasion in A549 cells while inducing dose-dependent apoptosis. These apoptotic responses and inhibition of tumor cell metastasis are accompanied by alterations in intracellular ROS levels and NAD+/NADH ratio. Furthermore, our in vivo experiment reveals that Sal B significantly suppresses A549 tumor growth compared to an untreated control group while promoting increased cleavage of caspase-3. Importantly, we observe that Sal B upregulates NDRG2 expression while downregulating p-PTEN and p-AKT expressions. Collectively, our results provide compelling evidence supporting the ability of Sal B to inhibit both growth and metastasis in A549 lung cancer cells through oxidative stress modulation as well as involvement of the NDRG2/PTEN/AKT pathway.

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Section: Discussionmentioning

confidence: 85%

Salvianolic acid B inhibits the growth and metastasis of A549 lung cancer cells through the NDRG2/PTEN pathway by inducing oxidative stress

Yang,

Huang,

Gao

et al. 2024

Preprint

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“…According to the established protocol, in vivo bioluminescence imaging was processed with minor modifications [ 29 ]. For bioluminescence imaging of MKN-45-luc and BGC-823-luc tumor-bearing mice, D-luciferin (15 mg/mL stock solution, 200 μL/mice, Gold Biotechnology) was inoculated into mice by the retro-orbital venous plexus using 30G needles.…”

Section: Methodsmentioning

confidence: 99%

Capsaicin orchestrates metastasis in gastric cancer via modulating expression of TRPV1 channels and driving gut microbiota disorder

Deng,

Yu,

Ruan

et al. 2023

Cell Commun Signal

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The association between capsaicin, the major natural pungent compound of chili peppers, and gastric cancer progression has engendered conflicting findings. In this work, we sought to explore the character of a high capsaicin diet in gastric cancer metastasis and its possible mechanism. The impact of high capsaicin consumption on gastric cancer metastasis was investigated in vivo (xenograft mouse and zebrafish models) and in vitro (biochemical and molecular assays). It was demonstrated that high diet of capsaicin gave rise to accelerate tumor metastasis, which was partially mediated by elevating the expression of transient receptor potential vanilloid 1 (TRPV1) in gastric cancer cells. Importantly, we found that genetic depletion of TRPV1 could reduce gastric cancer metastasis by diminishing the motility of tumor cells in vitro, but acted poorly in xenograft mouse model. Considering the distribution of capsaicin in vivo, 16S rRNA sequencing and fecal microbiota transplantation (FMT) were used to appraise whether the gut microbiota involved in the high capsaicin diet induced metastasis. It was demonstrated that the level of Firmicutes and Clostridiales was expressively boosted following the high consumption of capsaicin. This microbial shift contributed to the increased peripheral 5-hydroxytryptamine (5-HT) levels, yielding the aggravated metastatic burden. Collectively, our findings highlighted the potential risk of high capsaicin diet in promoting gastric cancer metastasis by virtue of modulating TRPV1 expression and gut microbiota composition, indicating the importance of controlled consumption of chili peppers for patients with gastric cancer.

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“…A wide range of mechanisms explain how phytochemicals benefit human health, and they offer special benefits in the treatment of conditions like diabetes, cancer, and cardiovascular disease (Qian et al, 2022; Zhang et al, 2018). Furthermore, because their primary mode of action is frequently against oxidative stress, phytochemicals are regarded as strong and effective weapons against a number of human ailments.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Advance in the pharmacological effects of quercetin in modulating oxidative stress and inflammation related disorders

Zhou

Qian

Tang

et al. 2023

Phytotherapy Research

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Numerous pharmacological effects of quercetin have been illustrated, including antiinflammation, antioxidation, and anticancer properties. In recent years, the antioxidant activity of quercetin has been extensively reported, in particular, its impacts on glutathione, enzyme activity, signaling transduction pathways, and reactive oxygen species (ROS). Quercetin has also been demonstrated to exert a striking antiinflammatory effect mainly by inhibiting the production of cytokines, reducing the expression of cyclooxygenase and lipoxygenase, and preserving the integrity of mast cells. By regulating oxidative stress and inflammation, which are regarded as two critical processes involved in the defense and regular physiological operation of biological systems, quercetin has been validated to be effective in treating a variety of disorders. Symptoms of these reactions have been linked to degenerative processes and metabolic disorders, including metabolic syndrome, cardiovascular, neurodegeneration, cancer, and nonalcoholic fatty liver disease. Despite that evidence demonstrates that antioxidants are employed to prevent excessive oxidative and inflammatory processes, there are still concerns regarding the expense, accessibility, and side effects of agents. Notably, natural products, especially those derived from plants, are widely accessible, affordable, and generally safe. In this review, the antioxidant and antiinflammatory abilities of the active ingredient quercetin and its application in oxidative stress‐related disorders have been outlined in detail.

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Pharmacological manipulation of Ezh2 with salvianolic acid B results in tumor vascular normalization and synergizes with cisplatin and T cell-mediated immunotherapy

Cited by 31 publications

References 62 publications

Salvianolic acid B inhibits the growth and metastasis of A549 lung cancer cells through the NDRG2/PTEN pathway by inducing oxidative stress

Salvianolic acid B inhibits the growth and metastasis of A549 lung cancer cells through the NDRG2/PTEN pathway by inducing oxidative stress

Capsaicin orchestrates metastasis in gastric cancer via modulating expression of TRPV1 channels and driving gut microbiota disorder

Advance in the pharmacological effects of quercetin in modulating oxidative stress and inflammation related disorders

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