Bufothionine induces autophagy in H22 hepatoma-bearing mice by inhibiting JAK2/STAT3 pathway, a possible anti-cancer mechanism of cinobufacini

Kong, Wei-Song; Shen, Fang-Xue; Xie, Rui-Fang; Zhou, Gui; Feng, Yiming; Zhou, Xin

doi:10.1016/j.jep.2021.113848

Cited by 16 publications

(10 citation statements)

References 30 publications

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“…and Pellina sp. p62/SQSTM1, LC3-II↑ Inhibit autophagy AsPC-1 and PANC-1 Pancreatic cancer [ 216 ] Indole-3-carbinol Cruciferous vegetables p62↓ LC3-II↑ Induce autophagy EAC cell Ehrlich ascites carcinoma [ 219 ] Mukonal Murraya koenigii Beclin-1↑ Induce autophagy MDA-MB-231; SK-BR-3 (IC 50 = 7.5 μM) Breast cancer [ 228 ] Evodiamine Evodia rutaecarpa Beclin-1↑ Induce autophagy SGC-7901 Gastric cancer [ 229 ] Bufothionine Toad Bufo bufo gargarizans Cantor JAK2/STAT3↓ Induce autophagy SMMC-7721 Hepatocellular carcinoma [ 233 ] Reduced scytonemin Nostoc commune ROS↑ LC3-II↑ Induce autophagy Jurkat (IC 50 = 1.8 μM) Leukemia [ 239 ] Fascaplysin Fascaplysinopsis sp. ROS, p8↑ …”

Section: Targeting Autophagic Signaling Pathways With Indole Alkaloid...mentioning

confidence: 99%

“…Bufothionine is the main component of cinobufacini injection with an anticancer effect. And a study demonstrates that bufothionine can inhibit proliferation and induce autophagy as a way to exert better anticancer effects [ 233 ]. Besides, in bufothionine-treated SMMC-7721 hepatocellular carcinoma cells, it could be observed that the concentration of IL-6 was decreased, the expression of p-Stat3-tyr705, p-Stat3ser727, and JAK2 was downregulated, as well as there was an increase in Atg5, Atg7, and LC3-II.…”

Section: Targeting Autophagic Signaling Pathways With Indole Alkaloid...mentioning

confidence: 99%

“…Besides, in bufothionine-treated SMMC-7721 hepatocellular carcinoma cells, it could be observed that the concentration of IL-6 was decreased, the expression of p-Stat3-tyr705, p-Stat3ser727, and JAK2 was downregulated, as well as there was an increase in Atg5, Atg7, and LC3-II. It suggested that bufothionine-induced autophagy in HCC was mediated by suppressing JAK2/STAT3 pathway [ 233 ].…”

Section: Targeting Autophagic Signaling Pathways With Indole Alkaloid...mentioning

confidence: 99%

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Naturally derived indole alkaloids targeting regulated cell death (RCD) for cancer therapy: from molecular mechanisms to potential therapeutic targets

et al. 2022

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Regulated cell death (RCD) is a critical and active process that is controlled by specific signal transduction pathways and can be regulated by genetic signals or drug interventions. Meanwhile, RCD is closely related to the occurrence and therapy of multiple human cancers. Generally, RCD subroutines are the key signals of tumorigenesis, which are contributed to our better understanding of cancer pathogenesis and therapeutics. Indole alkaloids derived from natural sources are well defined for their outstanding biological and pharmacological properties, like vincristine, vinblastine, staurosporine, indirubin, and 3,3′-diindolylmethane, which are currently used in the clinic or under clinical assessment. Moreover, such compounds play a significant role in discovering novel anticancer agents. Thus, here we systemically summarized recent advances in indole alkaloids as anticancer agents by targeting different RCD subroutines, including the classical apoptosis and autophagic cell death signaling pathways as well as the crucial signaling pathways of other RCD subroutines, such as ferroptosis, mitotic catastrophe, necroptosis, and anoikis, in cancer. Moreover, we further discussed the cross talk between different RCD subroutines mediated by indole alkaloids and the combined strategies of multiple agents (e.g., 3,10-dibromofascaplysin combined with olaparib) to exhibit therapeutic potential against various cancers by regulating RCD subroutines. In short, the information provided in this review on the regulation of cell death by indole alkaloids against different targets is expected to be beneficial for the design of novel molecules with greater targeting and biological properties, thereby facilitating the development of new strategies for cancer therapy. Graphic abstract

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Section: Targeting Autophagic Signaling Pathways With Indole Alkaloid...mentioning

confidence: 99%

Section: Targeting Autophagic Signaling Pathways With Indole Alkaloid...mentioning

confidence: 99%

Section: Targeting Autophagic Signaling Pathways With Indole Alkaloid...mentioning

confidence: 99%

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Naturally derived indole alkaloids targeting regulated cell death (RCD) for cancer therapy: from molecular mechanisms to potential therapeutic targets

et al. 2022

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“…Then, it inhibits gene expression regulated by STAT3, downregulates gene expression related to cell proliferation, survival, apoptosis and invasion, activates apoptotic protein-3 and apoptotic protein-9, and thus promotes the dependent apoptosis of liver cancer cells (108). In addition, bufothionine induces autophagy in HCC by inhibiting JAK2/STAT3 pathway (109). These indicate that regulating IL-6/JAK2/STAT3 signaling pathway may be a therapeutic strategy for liver cancer.…”

Section: Liver Cancermentioning

confidence: 96%

The role of IL-6/JAK2/STAT3 signaling pathway in cancers

2022

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Interleukin-6 (IL-6) is a pleiotropic cytokine involved in immune regulation. It can activate janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) signaling pathway. As one of the important signal transduction pathways in cells, JAK2/STAT3 signaling pathway plays a critical role in cell proliferation and differentiation by affecting the activation state of downstream effector molecules. The activation of JAK2/STAT3 signaling pathway is involved in tumorigenesis and development. It contributes to the formation of tumor inflammatory microenvironment and is closely related to the occurrence and development of many human tumors. This article focuses on the relationship between IL-6/JAK2/STAT3 signaling pathway and liver cancer, breast cancer, colorectal cancer, gastric cancer, lung cancer, pancreatic cancer and ovarian cancer, hoping to provide references for the research of cancer treatment targeting key molecules in IL-6/JAK2/STAT3 signaling pathway.

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“…In additional, bufotenines such as bufobutanoic acid and bufopyramide were demonstrated could inhibit mice P388 lymphocytic leukemia cell ( 22 ). Bufothionine, the most focused and widely studied indole alkaloids of ChanSu which have been verified possess notable anti-tumor effect on various cancer cells, including liver cancer ( 23 ), gastric cancer ( 24 ). Since the pharmaceutical active components of ChanSu and the pathogenic factors of cancers are overly complicated ( 25 ), despite an increasing number of medical scientists participating in the research of ChanSu active components, the action mechanisms of a portion of active components remain to be further studied.…”

Section: Introductionmentioning

confidence: 99%

A research update on the antitumor effects of active components of Chinese medicine ChanSu

Jia

Zheng

et al. 2022

Front. Oncol.

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Clinical data show that the incidence and mortality rates of cancer are rising continuously, and cancer has become an ongoing public health challenge worldwide. Excitingly, the extensive clinical application of traditional Chinese medicine may suggest a new direction to combat cancer, and the therapeutic effects of active ingredients from Chinese herbal medicine on cancer are now being widely studied in the medical community. As a traditional anticancer Chinese medicine, ChanSu has been clinically applied since the 1980s and has achieved excellent antitumor efficacy. Meanwhile, the ChanSu active components (e.g., telocinobufagin, bufotalin, bufalin, cinobufotalin, and cinobufagin) exert great antitumor activity in many cancers, such as breast cancer, colorectal cancer, hepatocellular carcinoma and esophageal squamous cell carcinoma. Many pharmaceutical scientists have investigated the anticancer mechanisms of ChanSu or the ChanSu active components and obtained certain research progress. This article reviews the research progress and antitumor mechanisms of ChanSu active components and proposes that multiple active components of ChanSu may be potential anticancer drugs.

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Bufothionine induces autophagy in H22 hepatoma-bearing mice by inhibiting JAK2/STAT3 pathway, a possible anti-cancer mechanism of cinobufacini

Cited by 16 publications

References 30 publications

Naturally derived indole alkaloids targeting regulated cell death (RCD) for cancer therapy: from molecular mechanisms to potential therapeutic targets

Naturally derived indole alkaloids targeting regulated cell death (RCD) for cancer therapy: from molecular mechanisms to potential therapeutic targets

The role of IL-6/JAK2/STAT3 signaling pathway in cancers

A research update on the antitumor effects of active components of Chinese medicine ChanSu

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