Bufothionine

Last updated
Bufothionine
Bufothionine Structure.png
Names
Preferred IUPAC name
5,5-Dimethyl-6-(sulfinooxy)-1,3,4,5-tetrahydropyrrolo[4,3,2-de]quinolin-5-ium
Identifiers
3D model (JSmol)
ChemSpider
PubChem CID
  • InChI=1S/C12H14N2O3S/c1-14(2)6-5-8-7-13-9-3-4-10(17-18(15)16)12(14)11(8)9/h3-4,7,13H,5-6H2,1-2H3/p+1
  • O=S(O)Oc1ccc2c3c1[N+](CCc3c[nH]2)(C)C
Properties
C12H15N2O3S+
Molar mass 267.32 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Bufothionine is a sulfur-containing compound which is present in the bufotoxins secreted by the parotoid gland of certain toads of the genera Bufo and Chaunus . This specific compound can be found in the skin of certain species of toad such as the Asiatic Toad, [1] [2] Chaunus arunco , Chaunus crucifer , Chaunus spinulosus , and Chaunus arenarum . [3]

Research

In ancient times, cinobufacini, which is extracted from the skin and the parotid venom glands of toad of the bufo genus [4] was used to treat symptoms like swelling and pain. In the present time, cinobufacinin injections are used to achieve satisfactory effect on Hepatocellular carcinoma (HCC) in China. [5] Bufothionine is a major active component of cinobufacini. Bufothionine has been shown to suppress growth of cancerous liver cells in vitro . In vivo, bufothionine has also been showing relieved symptoms and anti inflammatory activities in tumor bearing mice. [5] Experiments were conducted in which cultured cancer cells were shown to have an increase in G2-M damage checkpoint, ensuring that growth of the cell will not continue until the damage to the DNA is corrected while also showing a drop in the G0 and G1 activity, which pertains to phase where there is cell growth and RNA production. [6]  

Bufothionine is shown to induce autophagy in hepatocellular carcinomas by inhibiting JAK2/STAT3 pathways, which may present possibilities of anti cancer mechanism in bufothionine through cinobufacini injections. [5] Similarly, bufothionine has also been shown to increase the chances of cell death and decrease cell growth of gastric cancer related cells by inhibiting the PIM3 gene, which, in cancerous cells, increases the resistance of chemotherapeutic treatments. [7] In glioblastoma multiforme (GBM), bufothionine presents anti-tumor activities in the GBM cells lines U87 and U373 by triggering endoplasmic reticulum stress to lead cell death in the U87 and U373 cells. [8]

Related Research Articles

Bufotoxins are a family of toxic steroid lactones or substituted tryptamines of which some are toxic. They occur in the parotoid glands, skin, and poison of many toads and other amphibians, and in some plants and mushrooms. The exact composition varies greatly with the specific source of the toxin.

Bufagin is a toxic steroid C24H34O5 obtained from toad's milk, the poisonous secretion of a skin gland on the back of the neck of a large toad (Rhinella marina, synonym Bufo marinus, the cane toad). The toad produces this secretion when it is injured, scared or provoked. Bufagin resembles chemical substances from digitalis in physiological activity and chemical structure.

<span class="mw-page-title-main">Bufotalin</span> Chemical compound

Bufotalin is a cardiotoxic bufanolide steroid, cardiac glycoside analogue, secreted by a number of toad species. Bufotalin can be extracted from the skin parotoid glands of several types of toad.

<span class="mw-page-title-main">Cardiotoxin III</span>

Cardiotoxin III is a sixty amino-acid polypeptide toxin from the Taiwan cobra Naja atra. CTX III is highly basic and hydrophobic protein. It is an example of a group of snake cardio/cytotoxins, which are made up of shorter snake venom three-finger toxins. Over 50 different cytotoxin polypeptides have been isolated and sequenced from venom samples. The difference in the CTX functionality may be due to the relatively small difference in the polypeptide's structure, allowing different CTXs to induce lysis in different cell types. The CTX III molecule contains multiple binding sites and is cytolytic for myocardial cells and human leukemic T cells.

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<span class="mw-page-title-main">RhoC</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">ARID1A</span> Protein-coding gene in humans

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<span class="mw-page-title-main">CKLF (gene)</span> Protein-coding gene in the species Homo sapiens

Chemokine-like factor (CKLF) is a member of the CKLF-like MARVEL transmembrane domain-containing family of proteins that in humans is encoded by the CKLF gene. This gene is located on band 22.1 in the long arm of chromosome 16.

<span class="mw-page-title-main">Arenobufagin</span> Chemical compound

Arenobufagin is a cardiotoxic bufanolide steroid secreted by the Argentine toad Bufo arenarum. It has effects similar to digitalis, blocking the Na+/K+ pump in heart tissue.

<span class="mw-page-title-main">Cinobufagin</span> Chemical compound

Cinobufagin is a cardiotoxic bufanolide steroid secreted by the Asiatic toad Bufo gargarizans. It has similar effects to digitalis and is used in traditional Chinese medicine.

mir-221 microRNA MicroRNA

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In molecular biology mir-638 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.

HuaChanSu is a traditional Chinese medicine extracted from the skin of toads from the genus Bufo that is believed by some to slow the spread of cancerous cells. The parotoid gland of toads of the Bufo genus secrete a venom, which is dried and dissolved in water. This solution, HuaChanSu, is injected into a cancerous area and targets specific cancer cells. HuaChanSu is undergoing further trials, and its effect is not completely understood.

Migration inducting gene 7 is a gene that corresponds to a cysteine-rich protein localized to the cell membrane and cytoplasm. It is the first-in-class of novel proteins translated from what are thought to be long Non-coding RNAs.

<span class="mw-page-title-main">Bufalin</span> Chemical compound

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<span class="mw-page-title-main">Cytoskeleton regulator RNA</span>

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Yu Baofa is a Chinese oncologist and researcher in intratumoral cancer therapy and drug development. He is the Founder, CEO and Chairman of Baofa Cancer Hospital Network China in Jinan, Beijing and Dongping. He also developed Ultra Minimum Incision Personalized Intra-Tumoral Chemo-Immuno (UMIPIC) Therapy.

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References

  1. ↑ Dai, L. P.; Gao, H. M.; Wang, Z. M.; Wang, W. H. (2007). "Isolation and structure identification of chemical constituents from the skin of Bufo bufo gargarizans". Yao Xue Xue Bao = Acta Pharmaceutica Sinica. 42 (8): 858–861. PMID   17944235.
  2. ↑ Dai, L. P.; Wang, Z. M.; Gao, H. M.; Jiang, X.; Ding, G. Z. (2007). "Determination of bufothionine in skin of Bufo bufo gargarizans and Huachansu injection". Zhongguo Zhong Yao Za Zhi = Zhongguo Zhongyao Zazhi = China Journal of Chinese Materia Medica. 32 (3): 224–226. PMID   17432144.
  3. ↑ V Deulofeu; Enrique Duprat (February 10, 1944). "The Basic Constituents of the Venom of some South American Toads" (PDF). Journal of Biological Chemistry . 153 (2). American Society for Biochemistry and Molecular Biology: 459–463. doi: 10.1016/S0021-9258(18)71987-X .
  4. ↑ Wang, Guojun; Liu, Guanghui; Ye, Yanwei; Fu, Yang; Zhang, Xiefu (September 2019). "Bufothionine exerts anti-cancer activities in gastric cancer through Pim3". Life Sciences. 232: 116615. doi:10.1016/j.lfs.2019.116615. PMID   31260686. S2CID   195772507.
  5. 1 2 3 Kong, Wei-Song; Shen, Fang-Xue; Xie, Rui-Fang; Zhou, Gui; Feng, Yi-Ming; Zhou, Xin (April 2021). "Bufothionine induces autophagy in H22 hepatoma-bearing mice by inhibiting JAK2/STAT3 pathway, a possible anti-cancer mechanism of cinobufacini". Journal of Ethnopharmacology. 270: 113848. doi:10.1016/j.jep.2021.113848. PMID   33485977. S2CID   231703160.
  6. ↑ Xie, Rui-Fang; Li, Zhi-Cheng; Gao, Bo; Shi, Zhi-Na; Zhou, Xin (2012-06-01). "Bufothionine, a possible effective component in cinobufocini injection for hepatocellular carcinoma". Journal of Ethnopharmacology. Modernization of Traditional Chinese Medicine. 141 (2): 692–700. doi:10.1016/j.jep.2011.12.018. ISSN   0378-8741. PMID   22210051.
  7. ↑ Wang, Guojun; Liu, Guanghui; Ye, Yanwei; Fu, Yang; Zhang, Xiefu (2019-09-01). "Bufothionine exerts anti-cancer activities in gastric cancer through Pim3". Life Sciences. 232: 116615. doi:10.1016/j.lfs.2019.116615. ISSN   0024-3205. PMID   31260686. S2CID   195772507.
  8. ↑ Sun, Yafeng; Zhang, Xianhong (November 2019). "Bufothionine Promotes Apoptosis via Triggering ER Stress and Synergizes with Temozolomide in Glioblastoma Multiforme Cells". The Anatomical Record. 302 (11): 1950–1957. doi: 10.1002/ar.24194 . ISSN   1932-8486. PMID   31177611. S2CID   182949594. (Retracted, see doi:10.1002/ar.24813, PMID   34708936 . If this is an intentional citation to a retracted paper, please replace {{ retracted |...}} with {{ retracted |...|intentional=yes}}.)
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