Bufalin Enhances Immune Responses in Leukemic Mice Through Enhancing Phagocytosis of Macrophage<i>In Vivo</i>

Shih, Yu‐Lueng; Chou, Jiann Shang; Chen, Yung Liang; Hsueh, Shu Ching; Chung, Hsueh Yu; Lee, Mei Hui; Chen, Chao-Ping; Lee, Ming Zhe; Hou, Hsin Tu; Lu, Hsu Feng; Chen, Kuo-Wei; Chung, Jing‐Gung

doi:10.21873/invivo.11355

Cited by 11 publications

(10 citation statements)

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“…Our previous findings have shown that bufalin caused apoptotic cell death in human nasopharyngeal carcinoma cells (24) and against lung cancer xenograft animals in vivo (25). Furthermore, we also found that bufalin promoted phagocytosis of macrophages in peripheral blood and the peritoneal cavity in leukemia mice in vivo (26).…”

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confidence: 55%

Combination Treatment of Sorafenib and Bufalin Induces Apoptosis in NCI-H292 Human Lung Cancer CellsIn Vitro

KUO

Liao

et al. 2022

In Vivo

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Background/Aim: Lung cancer notably contributes to tumor-associated mortality worldwide, and standard chemotherapy is used for lung cancer patients. However, its therapeutic efficacy remains unsatisfactory. This study aimed to evaluate the effects and molecular mechanisms of sorafenib and bufalin combination therapy on lung cancer cells in vitro. Materials and Methods: NCI-H292 cells were treated with sorafenib, bufalin, and sorafenib in combination with bufalin. Cell viability, ROS production, Ca 2+ release, and mitochondrial membrane potential were examined by flow cytometric assay. Annexin V/PI staining and chromatin condensation were examined by the apoptosis assays. Finally the molecular mechanism of apoptosis-associated protein expression was investigated by western blotting. Results: NCI-H292 cells treated with sorafenib in combination with bufalin showed significantly decreased viability, enhanced cellular apoptosis, and DNA condensation when compared to that with sorafenib or bufalin alone. Moreover, the combination treatment exhibited higher reactive oxygen species (ROS) production and lower mitochondrial membrane potential (ΔΨm). The combined treatment resulted in higher expression of SOD but lower catalase compared to sorafenib treatment alone. Compared to sorafenib or bufalin treatment alone, the combination treatment resulted in lower Bcl-2 expression but higher Bax, Bad, APAF-1, caspase-3, and caspase-9. Conclusion: Sorafenib in combination with bufalin shows more potent cytotoxic effects and cell apoptosis than sorafenib or bufalin treatment alone in NCI-H292 cells. The combined treatment significantly enhanced apoptotic cell death in NCI-H292 lung cancer cells by activating ROS-, mitochondria-, and caspase-signaling pathways in vitro.Cancer affects human health globally with its incidence being the most severe public issue of the 21 st century. The global number of lung cancer deaths remains high yearly (1). Lung cancers are mainly divided into two subtypes, including nonsmall cell lung cancer (NSCLC) and small cell lung cancer (SCLC). However, the NSCLC subtype occupies about 80-85% of lung cancers (2). Currently, patients undergo surgery, radiation, chemotherapy, and targeted therapy as the most commonly used strategies for lung cancer. Yet clinical outcomes of current therapies remain unsatisfactory: the 5year survival rate of lung cancer patients is less than 15% (3), and that of patients with metastatic disease is less than 10% 582 This article is freely accessible online.

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confidence: 55%

Combination Treatment of Sorafenib and Bufalin Induces Apoptosis in NCI-H292 Human Lung Cancer CellsIn Vitro

KUO

Liao

et al. 2022

In Vivo

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“…YUNG‐LUEN SHIH and colleagues found that bufalin increased the body weight, but reduced liver and spleen weights, and reduced CD3, CD16 and Mac‐3 cell markers. They finally conclude that bufalin may modulate immune responses not only through increasing monocyte (CD11b) population and T‐ and B‐cell proliferation, but also by increasing macrophage phagocytosis in leukaemic mice in vivo 42 . Marco Busnelli and colleagues found that fenretinide, a synthetic retinoid derivative, could induce spleen abnormally enlarged and markedly increased atherosclerotic lesions at the aortic arch, thoracic and abdominal aorta of fenretinide‐treated mice, just the similar results in our control (western diet) group 43 .…”

Section: Discussionmentioning

confidence: 96%

Acacetin exerts antioxidant potential against atherosclerosis through Nrf2 pathway in apoE^−/− Mice

Song

et al. 2020

J Cellular Molecular Medi

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“…[ 61 ]. The research group of Shih et al also presented a study of a bufadienolide bufalin, which affected the immune system of mice comparably to ouabain [ 62 ]. Bufalin was also described to inhibit hepatocellular carcinoma (HCC) proliferation and migration.…”

Section: Immunomodulatory Action Of Cgs In Cancer Treatmentmentioning

confidence: 99%

Cardiac Glycosides as Immune System Modulators

2021

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Cardiac glycosides (CGs) are natural steroid compounds occurring both in plants and animals. They are known for long as cardiotonic agents commonly used for various cardiac diseases due to inhibition of Na+/K+-ATPase (NKA) pumping activity and modulating heart muscle contractility. However, recent studies show that the portfolio of diseases potentially treatable with CGs is much broader. Currently, CGs are mostly studied as anticancer agents. Their antiproliferative properties are based on the induction of multiple signaling pathways in an NKA signalosome complex. In addition, they are strongly connected to immunogenic cell death, a complex mechanism of induction of anticancer immune response. Moreover, CGs exert various immunomodulatory effects, the foremost of which are connected with suppressing the activity of T-helper cells or modulating transcription of many immune response genes by inhibiting nuclear factor kappa B. The resulting modulations of cytokine and chemokine levels and changes in immune cell ratios could be potentially useful in treating sundry autoimmune and inflammatory diseases. This review aims to summarize current knowledge in the field of immunomodulatory properties of CGs and emphasize the large area of potential clinical use of these compounds.

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Bufalin Enhances Immune Responses in Leukemic Mice Through Enhancing Phagocytosis of MacrophageIn Vivo

Abstract: Bufalin increased immune responses by enhancing phagocytosis in mice with leukemia mice.

Cited by 11 publications

References 31 publications

Combination Treatment of Sorafenib and Bufalin Induces Apoptosis in NCI-H292 Human Lung Cancer CellsIn Vitro

Combination Treatment of Sorafenib and Bufalin Induces Apoptosis in NCI-H292 Human Lung Cancer CellsIn Vitro

Acacetin exerts antioxidant potential against atherosclerosis through Nrf2 pathway in apoE^−/− Mice

Cardiac Glycosides as Immune System Modulators

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Bufalin Enhances Immune Responses in Leukemic Mice Through Enhancing Phagocytosis of MacrophageIn Vivo

Abstract: Bufalin increased immune responses by enhancing phagocytosis in mice with leukemia mice.

Cited by 11 publications

References 31 publications

Combination Treatment of Sorafenib and Bufalin Induces Apoptosis in NCI-H292 Human Lung Cancer CellsIn Vitro

Combination Treatment of Sorafenib and Bufalin Induces Apoptosis in NCI-H292 Human Lung Cancer CellsIn Vitro

Acacetin exerts antioxidant potential against atherosclerosis through Nrf2 pathway in apoE−/− Mice

Cardiac Glycosides as Immune System Modulators

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Product

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Acacetin exerts antioxidant potential against atherosclerosis through Nrf2 pathway in apoE^−/− Mice