Arenobufagin, isolated from toad venom, inhibited epithelial-to-mesenchymal transition and suppressed migration and invasion of lung cancer cells via targeting IKKβ/NFκB signal cascade

Zhao, Jing; Zhang, Qiansen; Zou, Gangyong; Gao, Guogang; Yue, Qing-Xi

doi:10.1016/j.jep.2019.112492

Cited by 22 publications

(11 citation statements)

References 46 publications

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“…ArBu possesses significant antineoplastic activity in vitro and in vivo. 18 , 19 , 20 , 22 , 36 , 37 This is associated the regulation of proliferation, cell cycle, apoptosis, autophagy, and migration. There are no reports on the modulation of ArBu on ferroptosis.…”

Section: Discussionmentioning

confidence: 99%

Arenobufagin causes ferroptosis in human gastric cancer cells by increasing rev-erbα expression

Chen

Wang

et al. 2023

Journal of Traditional and Complementary Medicine

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Section: Discussionmentioning

confidence: 99%

Arenobufagin causes ferroptosis in human gastric cancer cells by increasing rev-erbα expression

Chen

Wang

et al. 2023

Journal of Traditional and Complementary Medicine

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“…Inhibition of HIF-1α synthesis suppresses PD-L1 expression and induces lysosomal degradation of PD-L1, enhancing the ability of CTLs to kill cancer cells. 427 The deletion of HIF-1α in NK cells significantly inhibits cancer growth and improves patient survival outcomes by activating the NF-κB pathway and stimulating the expression of effector molecules, such as IL-18. 428 Single inhibition of HIF-1α in immune cells restores immune cytotoxicity; however, it also induces PD-L1 expression in cancer cells, impairing anticancer immunity.…”

Section: Hypoxia and Immunotherapymentioning

confidence: 99%

Hypoxic microenvironment in cancer: molecular mechanisms and therapeutic interventions

Zhou

Han

et al. 2023

Sig Transduct Target Ther

264

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Having a hypoxic microenvironment is a common and salient feature of most solid tumors. Hypoxia has a profound effect on the biological behavior and malignant phenotype of cancer cells, mediates the effects of cancer chemotherapy, radiotherapy, and immunotherapy through complex mechanisms, and is closely associated with poor prognosis in various cancer patients. Accumulating studies have demonstrated that through normalization of the tumor vasculature, nanoparticle carriers and biocarriers can effectively increase the oxygen concentration in the tumor microenvironment, improve drug delivery and the efficacy of radiotherapy. They also increase infiltration of innate and adaptive anti-tumor immune cells to enhance the efficacy of immunotherapy. Furthermore, drugs targeting key genes associated with hypoxia, including hypoxia tracers, hypoxia-activated prodrugs, and drugs targeting hypoxia-inducible factors and downstream targets, can be used for visualization and quantitative analysis of tumor hypoxia and antitumor activity. However, the relationship between hypoxia and cancer is an area of research that requires further exploration. Here, we investigated the potential factors in the development of hypoxia in cancer, changes in signaling pathways that occur in cancer cells to adapt to hypoxic environments, the mechanisms of hypoxia-induced cancer immune tolerance, chemotherapeutic tolerance, and enhanced radiation tolerance, as well as the insights and applications of hypoxia in cancer therapy.

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“…Some differences with the Peruvian R. marina are the occurrence of arenobufagin derivatives and a higher number of oxidized compounds in R. horribilis compared with the Amazonian species. Interestingly, most of the compounds reported in the R. horribilis PGS have been previously described from South American Rhinella species [9,10,18] and/or from the crude drug Venenum Bufonis or Ch'an Su from China and Eastern Asia [27,30,31], which exhibit anti-cancer effects in several cancer cell lines [35][36][37][38][39][40]. Based on this, we propose to evaluate the anti-cancer effect of crude PGS of R. horribilis and their fractions A, B, and C.…”

Section: Argininyl Diacids Of Bufadienolidesmentioning

confidence: 99%

The Parotoid Gland Secretion from Peruvian Toad Rhinella horribilis (Wiegmann, 1833): Chemical Composition and Effect on the Proliferation and Migration of Lung Cancer Cells

Schmeda-Hirschmann

Andrade

Soto-Vásquez

et al. 2020

Toxins

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Since Rhinella sp. toads produce bioactive substances, some species have been used in traditional medicine and magical practices by ancient cultures in Peru. During several decades, the Rhinella horribilis toad was confused with the invasive toad Rhinella marina, a species documented with extensive toxinological studies. In contrast, the chemical composition and biological effects of the parotoid gland secretions (PGS) remain still unknown for R. horribilis. In this work, we determine for the first time 55 compounds from the PGS of R. horribilis, which were identified using HPLC-MS/MS. The crude extract inhibited the proliferation of A549 cancer cells with IC50 values of 0.031 ± 0.007 and 0.015 ± 0.001 µg/mL at 24 and 48 h of exposure, respectively. Moreover, it inhibited the clonogenic capacity, increased ROS levels, and prevented the etoposide-induced apoptosis, suggesting that the effect of R. horribilis poison secretion was by cell cycle blocking before of G2/M-phase checkpoint. Fraction B was the most active and strongly inhibited cancer cell migration. Our results indicate that the PGS of R. horribilis are composed of alkaloids, bufadienolides, and argininyl diacids derivatives, inhibiting the proliferation and migration of A549 cells.

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Arenobufagin, isolated from toad venom, inhibited epithelial-to-mesenchymal transition and suppressed migration and invasion of lung cancer cells via targeting IKKβ/NFκB signal cascade

Cited by 22 publications

References 46 publications

Arenobufagin causes ferroptosis in human gastric cancer cells by increasing rev-erbα expression

Arenobufagin causes ferroptosis in human gastric cancer cells by increasing rev-erbα expression

Hypoxic microenvironment in cancer: molecular mechanisms and therapeutic interventions

The Parotoid Gland Secretion from Peruvian Toad Rhinella horribilis (Wiegmann, 1833): Chemical Composition and Effect on the Proliferation and Migration of Lung Cancer Cells

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