bufanolides

Summary

Summary: Cyclopentanophenanthrenes with a 6-membered lactone ring attached at the 17-position and SUGARS attached at the 3-position. They are found in BUFONIDAE and often possess cardiotonic properties.

Top Publications

  1. Zhang L, Nakaya K, Yoshida T, Kuroiwa Y. Induction by bufalin of differentiation of human leukemia cells HL60, U937, and ML1 toward macrophage/monocyte-like cells and its potent synergistic effect on the differentiation of human leukemia cells in combination with other inducers. Cancer Res. 1992;52:4634-41 pubmed
    ..These results suggest that bufalin in combination with VP16, all-trans retinoic acid, 1 alpha,25-dihydroxyvitamin D3, rTNF-alpha, or gamma-interferon may be very useful in the differentiation of human leukemia. ..
  2. Cao Hong -, Shibayama Imazu T, Masuda Y, Shinki T, Nakajo S, Nakaya K. Involvement of Tiam1 in apoptosis induced by bufalin in HeLa cells. Anticancer Res. 2007;27:245-9 pubmed
    ..Our results suggest that Tiam1 is a downstream mediator of bufalin-induced apoptosis in the human solid tumor HeLa cell line, as well as in leukemia cell lines. ..
  3. Dong Y, Yin S, Li J, Jiang C, Ye M, Hu H. Bufadienolide compounds sensitize human breast cancer cells to TRAIL-induced apoptosis via inhibition of STAT3/Mcl-1 pathway. Apoptosis. 2011;16:394-403 pubmed publisher
    ..Our findings for the first time provided strong evidences that bufadienolide compounds have excellent potential to be developed as a novel class of sensitizers of TRAIL. ..
  4. Supratman U, Fujita T, Akiyama K, Hayashi H, Murakami A, Sakai H, et al. Anti-tumor promoting activity of bufadienolides from Kalanchoe pinnata and K. daigremontiana x tubiflora. Biosci Biotechnol Biochem. 2001;65:947-9 pubmed
    ..Bryophyllin C (2), a reduction analogue of 1, and bersaldegenin-3-acetate (3) lacking the orthoacetate moiety were less active. These results strongly suggest that bufadienolides are potential cancer chemopreventive agents. ..
  5. Ko W, Park T, Park C, Kim Y, Yoon H, Lee S, et al. Induction of apoptosis by Chan Su, a traditional Chinese medicine, in human bladder carcinoma T24 cells. Oncol Rep. 2005;14:475-80 pubmed
    ..Taken together, these findings partially provide novel insights into the possible molecular mechanisms of the anti-cancer activity of Chan Su. ..
  6. Lu C, Nan K, Lei Y. Agents from amphibians with anticancer properties. Anticancer Drugs. 2008;19:931-9 pubmed publisher
    ..This paper discusses the medical and pharmaceutical significance of products derived from amphibians. ..
  7. Bick R, Poindexter B, Sweney R, Dasgupta A. Effects of Chan Su, a traditional Chinese medicine, on the calcium transients of isolated cardiomyocytes: cardiotoxicity due to more than Na, K-ATPase blocking. Life Sci. 2002;72:699-709 pubmed
  8. Gao H, Zehl M, Kaehlig H, Schneider P, Stuppner H, Moreno Y Banuls L, et al. Rapid structural identification of cytotoxic bufadienolide sulfates in toad venom from Bufo melanosticus by LC-DAD-MS(n) and LC-SPE-NMR. J Nat Prod. 2010;73:603-8 pubmed publisher
    ..Compound 3 and hellebrin displayed similar and marked in vitro cytotoxicity. ..
  9. Li D, Qu X, Hou K, Zhang Y, Dong Q, Teng Y, et al. PI3K/Akt is involved in bufalin-induced apoptosis in gastric cancer cells. Anticancer Drugs. 2009;20:59-64 pubmed publisher
    ..These results suggested that the PI3K/Akt pathway might play a key role in bufalin-induced apoptosis in gastric cancer MGC803 cells. ..

More Information

Publications61

  1. Pastor N, Cortés F. Bufalin influences the repair of X-ray-induced DNA breaks in Chinese hamster cells. DNA Repair (Amst). 2003;2:1353-60 pubmed
    ..The possible involvement of topo II in radiation damage repair is discussed. ..
  2. Yu C, Kan S, Pu H, Jea Chien E, Wang P. Apoptotic signaling in bufalin- and cinobufagin-treated androgen-dependent and -independent human prostate cancer cells. Cancer Sci. 2008;99:2467-76 pubmed publisher
    ..The upstream mediators might be p53 and Fas in androgen-dependent LNCaP cells and Fas in androgen-independent DU145 and PC3 cells. ..
  3. Hayes R, Crossland M, Hagman M, Capon R, Shine R. Ontogenetic variation in the chemical defenses of cane toads (Bufo marinus): toxin profiles and effects on predators. J Chem Ecol. 2009;35:391-9 pubmed publisher
    ..Our results suggest a dramatic ontogenetic shift in the danger that toads pose to native predators, reflecting rapid changes in the types and amounts of toxins during toad development...
  4. Supratman U, Fujita T, Akiyama K, Hayashi H. New insecticidal bufadienolide, bryophyllin C, from Kalanchoe pinnata. Biosci Biotechnol Biochem. 2000;64:1310-2 pubmed
    ..Compounds 1 and 2 showed strong insecticidal activity against third instar larvae of the silkworm (Bombyx mori), their LD50 values being evaluated as 3 and 5 microg/g of diet, respectively. ..
  5. Amano Y, Cho Y, Matsunawa M, Komiyama K, Makishima M. Increased nuclear expression and transactivation of vitamin D receptor by the cardiotonic steroid bufalin in human myeloid leukemia cells. J Steroid Biochem Mol Biol. 2009;114:144-51 pubmed publisher
    ..Thus, the Na(+),K(+)-ATPase inhibitor bufalin modulates VDR function through several mechanisms, including Erk MAP kinase activation and increased nuclear VDR expression...
  6. Li H, Wang P, Gao Y, Zhu X, Liu L, Cohen L, et al. Na+/K+-ATPase ?3 mediates sensitivity of hepatocellular carcinoma cells to bufalin. Oncol Rep. 2011;25:825-30 pubmed publisher
    ..Thus, our study suggests that Na+/K+-ATPase ?3 might serve as a therapeutic target for bufalin in HCC, and its expression status may help predict sensitivity of HCC cells to bufalin treatment. ..
  7. Arnaud Batista F, Costa G, Oliveira I, Costa P, Santos C, Fonteles M, et al. Natriuretic effect of bufalin in isolated rat kidneys involves activation of the Na+-K+-ATPase-Src kinase pathway. Am J Physiol Renal Physiol. 2012;302:F959-66 pubmed publisher
    ..The present study shows for the first time the direct diuretic, natriuretic, and kaliuretic effects of bufalin in isolated rat kidney and the relevance of Na(+)-K(+)-ATPase-mediated signal transduction. ..
  8. Han K, Huang G, Gu W, Su Y, Huang X, Ling C. Anti-tumor activities and apoptosis-regulated mechanisms of bufalin on the orthotopic transplantation tumor model of human hepatocellular carcinoma in nude mice. World J Gastroenterol. 2007;13:3374-9 pubmed
    ..This apoptosis may be mediated mainly via up-regulating the expression of apoptosis-regulated gene bax, which may be involved in its anti-tumor mechanism of bufalin. ..
  9. Huang C, Chen A, Guo M, Yu J. Membrane dielectric responses of bufalin-induced apoptosis in HL-60 cells detected by an electrorotation chip. Biotechnol Lett. 2007;29:1307-13 pubmed
    ..The results demonstrate that the ROT technique gives a quantitative analysis of the toxic damage by chemicals to cells and can be exploited in the testing and development of new pharmaceuticals and active cell agents. ..
  10. Yin J, Shen J, Su W, Wang J, Huang G, Jin S, et al. Bufalin induces apoptosis in human osteosarcoma U-2OS and U-2OS methotrexate300-resistant cell lines. Acta Pharmacol Sin. 2007;28:712-20 pubmed
    ..The apoptosis-inducing effect of bufalin was not influenced by the presence of high levels of the DHFR protein. ..
  11. Zhang L, Nakaya K, Yoshida T, Kuroiwa Y. Bufalin as a potent inducer of differentiation of human myeloid leukemia cells. Biochem Biophys Res Commun. 1991;178:686-93 pubmed
    ..These findings suggest that bufalin might have potentiality as a new agent in the differentiation therapy for human myelogenous leukemia. ..
  12. Wu P, Hsu Y, Wu T, Bastow K, Lee K. Kalanchosides A-C, new cytotoxic bufadienolides from the aerial parts of Kalanchoe gracilis. Org Lett. 2006;8:5207-10 pubmed
    ..All eight isolated compounds showed significant cytotoxic activity against a panel of human tumor cell lines, with potency reaching the nanomolar range. However, only bryophyllin B (8) inhibited HIV replication in H9 lymphocyte cells...
  13. Nogawa T, Kamano Y, Yamashita A, Pettit G. Isolation and structure of five new cancer cell growth inhibitory bufadienolides from the Chinese traditional drug Ch'an Su. J Nat Prod. 2001;64:1148-52 pubmed
    ..Bufadienolides 1-5 provided significant inhibitory activity against the KB and HL-60 cancer cell lines. In addition, bufadienolide 1 was found active against the MH-60 cancer cell line. ..
  14. Hu K, Zhu L, Liang H, Hu F, Feng J. Improved antitumor efficacy and reduced toxicity of liposomes containing bufadienolides. Arch Pharm Res. 2011;34:1487-94 pubmed publisher
    ..5 times the LD(50) of bufadienolides solution and caused no allergen-related or blood vessel irritation effects. All these results proved that poloxamer modified bufadienolides liposomes have improved antitumor efficacy and safety. ..
  15. Tian X, Luo Y, Liu Y, Hou K, Jin B, Zhang J, et al. [Downregulation of Bcl-2 and survivin expression and release of Smac/DIABLO involved in bufalin-induced HL-60 cell apoptosis]. Zhonghua Xue Ye Xue Za Zhi. 2006;27:21-4 pubmed
    ..The mitochondria-mediated apoptotic pathway may be involved in the apoptosis induced by bufalin in HL-60 cells. ..
  16. Takai N, Ueda T, Nishida M, Nasu K, Narahara H. Bufalin induces growth inhibition, cell cycle arrest and apoptosis in human endometrial and ovarian cancer cells. Int J Mol Med. 2008;21:637-43 pubmed
    ..These results suggest that bufalin may become a useful adjuvant therapy for endometrial and ovarian cancers with minimal side effects. ..
  17. Ye M, Guo D. Analysis of bufadienolides in the Chinese drug ChanSu by high-performance liquid chromatography with atmospheric pressure chemical ionization tandem mass spectrometry. Rapid Commun Mass Spectrom. 2005;19:1881-92 pubmed
    ..A total of 35 bufadienolides were identified, including four new constituents. The method established here facilitated the convenient and rapid quality control of ChanSu crude drug and its pharmaceutical preparations. ..
  18. Liu D, Feng J. [Determination of apparent aqueous solubility and apparent oil-water partition coefficients of three bufadienolides composition]. Zhongguo Zhong Yao Za Zhi. 2008;33:1256-8 pubmed
    ..RBG, CBG, BL are liposoluble components and the sequence of log P is RBG > BL > CBG. RBG, CBG, BL is water-insoluble and hydrophobic. Surfactants can be applied to increase the solubility of three bufadienolides composition. ..
  19. Yeh J, Huang W, Kan S, Wang P. Effects of bufalin and cinobufagin on the proliferation of androgen dependent and independent prostate cancer cells. Prostate. 2003;54:112-24 pubmed
    ..Bufalin and cinobufagin may inhibit the proliferation of prostate cancer cell lines associated with sustained elevation of the [Ca(2+)](i) and that of apoptosis. ..
  20. Chen A, Yu J, Zhang L, Sun Y, Zhang Y, Guo H, et al. Microarray and biochemical analysis of bufalin-induced apoptosis of HL-60 Cells. Biotechnol Lett. 2009;31:487-94 pubmed publisher
    ..Our study provides new insights into the molecular mechanisms of bufalin, might prove to be beneficial in leukemia therapy. ..
  21. Kostakis C, Byard R. Sudden death associated with intravenous injection of toad extract. Forensic Sci Int. 2009;188:e1-5 pubmed publisher
    ..It also shows the difficulties that may be associated with attempting to identify low levels of organic toxins in postmortem specimens necessitating a targeted screening approach guided by information obtained at the death scene...
  22. Li F, Wang Y, Liu Z, Lin X, He H, Tang X. Formulation and characterization of bufadienolides-loaded nanostructured lipid carriers. Drug Dev Ind Pharm. 2010;36:508-17 pubmed publisher
    ..These results indicated that NLC could be developed as a carrier with improved drug plasma stability and offering controlled drug release. ..
  23. Song H, Guo T, Bi K, Wang H, Zhang R. Determination of resibufogenin and cinobufagin in heart-protecting musk pill by HPLC. Biomed Chromatogr. 2000;14:130-2 pubmed
    ..5 ng for resibufogenin and 2.0 ng for cinobufagin at a signal-to-noise ratio of 4:1. It is a rapid, simple and accurate method for quantitative analysis of resibufogenin and cinobufagin in heart-protecting musk pill. ..
  24. Xie C, Chan W, Yu S, Zhao J, Cheng C. Bufalin induces autophagy-mediated cell death in human colon cancer cells through reactive oxygen species generation and JNK activation. Free Radic Biol Med. 2011;51:1365-75 pubmed publisher
    ..Our findings unveil a novel mechanism of drug action by bufalin in colon cancer cells and open up the possibility of treating colorectal cancer through a ROS-dependent autophagy pathway. ..
  25. Cui X, Inagaki Y, Xu H, Wang D, Qi F, Kokudo N, et al. Anti-hepatitis B virus activities of cinobufacini and its active components bufalin and cinobufagin in HepG2.2.15 cells. Biol Pharm Bull. 2010;33:1728-32 pubmed
    ..Results suggested that cinobufacini had more potent activity against HBV antigen secretion than its components bufalin and cinobufagin and this inhibitory role was attributed to the specific inhibition of HBV mRNA expression. ..
  26. Gao H, Zehl M, Leitner A, Wu X, Wang Z, Kopp B. Comparison of toad venoms from different Bufo species by HPLC and LC-DAD-MS/MS. J Ethnopharmacol. 2010;131:368-76 pubmed publisher
    ..Toad venom, called Chansu in China, has been widely used for the treatment of heart failure, sores, pains, and various cancers for a long time in clinic...
  27. Daniel D, Süsal C, Kopp B, Opelz G, Terness P. Apoptosis-mediated selective killing of malignant cells by cardiac steroids: maintenance of cytotoxicity and loss of cardiac activity of chemically modified derivatives. Int Immunopharmacol. 2003;3:1791-801 pubmed
    ..The description of compounds without cardiac activity but with tumor-specific cytotoxicity suggests the potential of using them in cancer therapy. ..
  28. Qin T, Zhao X, Yun J, Zhang L, Ruan Z, Pan B. Efficacy and safety of gemcitabine-oxaliplatin combined with huachansu in patients with advanced gallbladder carcinoma. World J Gastroenterol. 2008;14:5210-6 pubmed
    ..GEMOX combined with huachansu (cinobufagin) injection is well tolerated, effective, thus improving the QOL of patients with advanced GBC. ..
  29. Takai N, Kira N, Ishii T, Yoshida T, Nishida M, Nishida Y, et al. Bufalin, a traditional oriental medicine, induces apoptosis in human cancer cells. Asian Pac J Cancer Prev. 2012;13:399-402 pubmed
    ..The compound is able to mediate inhibition of cell growth, cell cycle arrest, apoptosis, and expression of genes related to the malignant phenotype in human cancer cells. ..
  30. Bhuiyan M, Fant M, Dasgupta A. Study on mechanism of action of Chinese medicine Chan Su: dose-dependent biphasic production of nitric oxide in trophoblastic BeWo cells. Clin Chim Acta. 2003;330:179-84 pubmed
    ..The presence of bufalin in Chan Su preparation was confirmed by thin layer chromatography (TLC) analysis. Chan Su as well as bufalin is able to modulate the production of NO in BeWo cell line. ..
  31. Tian X, Wang P, Liu Y, Hou K, Jin B, Luo Y, et al. [Effect of bufalin-inducing apoptosis on Bcl-2 and PKC in HL-60 cells]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2007;15:67-71 pubmed
    ..It is concluded that apoptosis induced by bufalin is associated with downregulation of protein expression, dephosphorylation, and cleavage of Bcl-2 in HL-60 cells. ..
  32. Nasu K, Nishida M, Ueda T, Takai N, Bing S, Narahara H, et al. Bufalin induces apoptosis and the G0/G1 cell cycle arrest of endometriotic stromal cells: a promising agent for the treatment of endometriosis. Mol Hum Reprod. 2005;11:817-23 pubmed
    ..Caspase-9-mediated cascade is involved in this mechanism. Therefore, bufalin could be used as a therapeutic agent for the treatment of endometriosis. ..
  33. Qi F, Inagaki Y, Gao B, Cui X, Xu H, Kokudo N, et al. Bufalin and cinobufagin induce apoptosis of human hepatocellular carcinoma cells via Fas- and mitochondria-mediated pathways. Cancer Sci. 2011;102:951-8 pubmed publisher
    ..Taken together, bufalin and cinobufagin induce apoptosis of HepG(2) cells via both Fas- and mitochondria-mediated pathways, and a Fas-mediated caspase-10-dependent pathway might play a crucial role. ..
  34. Yun H, Yoo H, Shin D, Hong S, Kim J, Cho C, et al. Apoptosis induction of human lung carcinoma cells by Chan Su (Venenum Bufonis) through activation of caspases. J Acupunct Meridian Stud. 2009;2:210-7 pubmed publisher
    ..Data from this study indicates that SVB induces the apoptosis of A549 cells through a signaling cascade of death receptor-mediated extrinsic and mitochondria-mediated intrinsic caspase pathways. ..
  35. Price Rees S, Brown G, Shine R. Interacting impacts of invasive plants and invasive toads on native lizards. Am Nat. 2012;179:413-22 pubmed publisher
    ..As a result, populations of lizards from areas previously exposed to these alien plants may be preadapted to deal with the toxins of the more recent anuran invader...
  36. Qu X, Zhao M, Liu Y, Teng Y, Qu J, Zhang Y, et al. [Effects of Bufalin on SYK and CBL family proteins in induction of HL-60 cell apoptosis]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2009;17:65-8 pubmed
    ..It is concluded that SYK activation and CBL protein down-regulation may be involved in Bufalin-induced HL-60 cell apoptosis. ..
  37. Fedorova O, Zhuravin I, Agalakova N, Yamova L, Talan M, Lakatta E, et al. Intrahippocampal microinjection of an exquisitely low dose of ouabain mimics NaCl loading and stimulates a bufadienolide Na/K-ATPase inhibitor. J Hypertens. 2007;25:1834-44 pubmed
    ..Intrahippocampal administration of a low-dose ouabain mimics effects of NaCl loading and stimulates marinobufagenin, which produces natriuresis, and inhibits the vascular sodium-pump, inducing an increase in BP. ..
  38. Dasgupta A, Wahed A, Culton L, Olsen M, Wells A, Actor J. Activated charcoal is more effective than equilibrium dialysis in removing Chinese medicines Chan Su and Dan Shen from serum and activated charcoal also prevents further absorption of these agents from G.I. tract in mice: monitoring the effect in cli. Clin Chim Acta. 2002;324:51-9 pubmed
    ..Activated charcoal is effective in preventing absorption of these Chinese medicines from the G.I. tract and can also remove these agents from the serum. ..
  39. Ye M, Qu G, Guo H, Guo D. Novel cytotoxic bufadienolides derived from bufalin by microbial hydroxylation and their structure-activity relationships. J Steroid Biochem Mol Biol. 2004;91:87-98 pubmed
  40. Cunha Filho G, Schwartz C, Resck I, Murta M, Lemos S, Castro M, et al. Antimicrobial activity of the bufadienolides marinobufagin and telocinobufagin isolated as major components from skin secretion of the toad Bufo rubescens. Toxicon. 2005;45:777-82 pubmed
    ..0 and 16.0 microg/mL for E. coli and both 128 microg/mL for S. aureus. Besides the antimicrobial activity both bufadienolides promoted an increase of the contraction force in isolated frog ventricle strips...
  41. Zvartau N, Conrady A, Sviryaev Y, Rotari O, Merkulova N, Kalinkin A, et al. Marinobufagenin in hypertensive patients with obstructive sleep apnea. Cell Mol Biol (Noisy-le-grand). 2006;52:24-7 pubmed
    ..Our observations suggest that MBG may be involved in the pathogenesis of hypertension in OSA, and may be a marker of OSA severity. ..
  42. Ma H, Zhang J, Jiang J, Zhou J, Xu H, Zhan Z, et al. Bilirubin attenuates bufadienolide-induced ventricular arrhythmias and cardiac dysfunction in guinea-pigs by reducing elevated intracellular Na(+) levels. Cardiovasc Toxicol. 2012;12:83-9 pubmed publisher
  43. Park J, Shin D, Lee Y, Cho C, Kim G, Kim W, et al. Apoptotic and anti-metastatic effects of the whole skin of Venenum bufonis in A549 human lung cancer cells. Int J Oncol. 2012;40:1210-9 pubmed publisher
    ..Our data also demonstrated that MMPs are critical targets of SVB-induced anti-invasiveness in A549 cells. ..
  44. Uddin M, Horvat D, Childs E, Puschett J. Marinobufagenin causes endothelial cell monolayer hyperpermeability by altering apoptotic signaling. Am J Physiol Regul Integr Comp Physiol. 2009;296:R1726-34 pubmed publisher
  45. Xu Z, Wang F, Gao M, Chen X, Shan N, Cheng S, et al. Cardiotonic steroids attenuate ERK phosphorylation and generate cell cycle arrest to block human hepatoma cell growth. J Steroid Biochem Mol Biol. 2011;125:181-91 pubmed publisher
    ..Currently, the first generation of CS-based anticancer drugs (UNBS1450 and Anvirzel) are in Phase I clinical trials. These data clearly support their potential use as cancer therapies. ..
  46. Su Y, Qiao S, Yang H, Yang C, Jin Y, Stahr F, et al. Titanate-silica mesostructured nanocables: synthesis, structural analysis and biomedical applications. Nanotechnology. 2010;21:065604 pubmed publisher
  47. Xiong X, Zhou Y. [Mechanisms of Chansu Injection in reversing multidrug resistance of HL60/ADM cells]. Nan Fang Yi Ke Da Xue Xue Bao. 2012;32:337-40 pubmed
    ..CHS can partly reverse MDR in HL60/ADM cells possibly by down-regulating MRP and GST-?, up-regulating NF-?B and iNOS, and promoting cell apoptosis, thereby increase ADM sensitivity of HL-60/ADM cells. ..
  48. Zhu Z, Deng S, Liu D, Zhang B, Sun H, Tian Y, et al. Isolation and identification of phase I metabolites of resibufogenin in rats. Xenobiotica. 2013;43:479-85 pubmed publisher
    ..3. On the basis of these identified metabolites, a possible metabolism pathway for 1 in rats has been proposed. This is the first systematic study on the phase I metabolites of resibufogenin. ..
  49. Yang Z, Teng Y, Wang H, Hou H. Enhancement of skin permeation of bufalin by limonene via reservoir type transdermal patch: formulation design and biopharmaceutical evaluation. Int J Pharm. 2013;447:231-40 pubmed publisher
    ..The bufalin patch was successfully applied to biopharmaceutical study in rats and demonstrated the feasibility of this transdermal formulation for future development and clinical trials. ..
  50. Tempone A, Pimenta D, Lebrun I, Sartorelli P, Taniwaki N, de Andrade H, et al. Antileishmanial and antitrypanosomal activity of bufadienolides isolated from the toad Rhinella jimi parotoid macrogland secretion. Toxicon. 2008;52:13-21 pubmed publisher
    ..This novel biological effect of R. jimi steroids could be used as a template for the design of new therapeutics against Leishmaniasis and American Trypanosomiasis...
  51. Yoshika M, Komiyama Y, Konishi M, Akizawa T, Kobayashi T, Date M, et al. Novel digitalis-like factor, marinobufotoxin, isolated from cultured Y-1 cells, and its hypertensive effect in rats. Hypertension. 2007;49:209-14 pubmed
    ..41+/-0.286 versus 0.34+/-0.064 ng/day, respectively). These data suggest that MBT, arginine-suberoyl ester of marinobufagenin, can be a novel digitalis-like factor with hypertensive action and is secreted from the adrenocortical cells. ..
  52. Zhang D, Liu J, Deng L, Chen M, Yiu A, Cao H, et al. Arenobufagin, a natural bufadienolide from toad venom, induces apoptosis and autophagy in human hepatocellular carcinoma cells through inhibition of PI3K/Akt/mTOR pathway. Carcinogenesis. 2013;34:1331-42 pubmed publisher
    ..This study may provide a rationale for future clinical application using arenobufagin as a chemotherapeutic agent for HCC. ..