Bufothionine, a possible effective component in cinobufocini injection for hepatocellular carcinoma

Xie, Rui-Fang; Li, Zhicheng; Gao, Bo; Shi, Zhi-Na; Zhou, Xin

doi:10.1016/j.jep.2011.12.018

Cited by 39 publications

(31 citation statements)

References 8 publications

(9 reference statements)

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“…It has also been used as an effective traditional Chinese medicine to treat conditions like swelling, pain and heart failure [32]. The present study was designed to investigate the effects of cinobufagin on cancer pain and its peripheral immunological analgesia mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Chinese herb cinobufagin-reduced cancer pain is associated with increased peripheral opioids by invaded CD3/4/8 lymphocytes

et al. 2016

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ObjectivesTo investigate the mechanism of cinobufagin-reduced cancer pain in mouse cancer pain model and in vitro cell co-culture system.MethodsFemale Kunming mice were randomly divided into 4 groups. One group of animals was set as normal control without any treatment. Other three groups of animals received H22 hepatoma cell inoculation in right hind paw. At day 9 after inoculation, mice in other three groups were injected intraperitoneally once a day for 8 days with the solvent, morphine or cinobufagin, respectively. The pain behavior was recorded daily. On the last day, all mice were sacrificed and xenograft tissues homogenate and plasma levels of β-endorphin (β-END), corticotropin-releasing factor (CRF) and interleukin-1β (IL-1β) were assessed by ELISA assay. Immunohistochemistry was performed to determine the expression of β-END, pro-opiomelanocortin (POMC) and the μ-opioid receptor (μ-OR) in the xenograft tissues. Immunofluorescence was used to localize lymphocytes with expression of CD3+, CD4+ and CD8+ in xenograft tumors and adjacent tissues. Mice splenic lymphocytes and H22 hepatoma carcinoma ascites cells were prepared for co-culture. β-END and CRF were detected in co-culture supernatants. The MTT assay and cytometry were used to assess cell proliferation. RT-PCR was conducted to determine the gene expression of POMC and Cathepsin L (CTSL). Chemotaxis was examined using a transwell-based migration assay.ResultsCompared to the model group, the thermal and mechanical pain thresholds were increased in mice after cinobufagin treatment. The expression of β-END and CRF in the plasma and tumor tissues of cinobufagin group were much higher than that of the model group mice, but the expression of IL-1β in the plasma and tumor tissues was much lower than that in the model group mice. Meanwhile, the expression of β-END, POMC and μ-OR proteins was significantly increased in the xenograft tissues from cinobufagin group. Lymphocyte population of CD3+, CD4+, CD8+ were also elevated in xenograft tumors and adjacent tissues. In the cell co-culture assays, the content of β-END in the supernatant was significantly increased by cinobufagin in a dose-dependent manner. Cinobufagin also largely increased the proliferation of immune cells and inhibited H22 hepatoma carcinoma cell proliferation in single or co-culture cell assays. Gene expression of POMC and CTSL in cinobufagin group was significantly up-regulated comparing to the control group. Finally, cinobufagin addition enhanced the migration of immune cells in transwell assay.ConclusionsCinobufagin-induced local analgesic effect might be associated with increased activity of POMC/β-END/μ-OR pathway released from invaded CD3/4/8 lymphocytes in cancer tissues.

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Section: Discussionmentioning

confidence: 99%

Chinese herb cinobufagin-reduced cancer pain is associated with increased peripheral opioids by invaded CD3/4/8 lymphocytes

et al. 2016

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“…HuangQin (Scutellaria baicalensis) is effective to inhibit cell growth and G2/M phase arrest accompanied by increased Cyclin E and downregulation of p53, ETS1 (Vets avian erythroblastosis virus E26 oncogene homolog 1), cell division cycle 25B (Cdc25B), p63, epidermal growth factor receptor (EGFR), ERK1/2, XIAP, HIF2alpha, and Cdc25C [138] . Bufothionine also can inhibit cell proliferation and arrest cell cycle at G2/M phase in liver cancer cells [139] . Rhein, a component from DaHuang (Rheum palmatum L. or Rheum tanguticum Maxim.…”

Section: Arresting Cell Cyclementioning

confidence: 99%

Traditional Chinese medicine for prevention and treatment of hepatocarcinoma: From bench to bedside

Wang

2015

WJH

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and other TCM syndromes (Zheng). Modern treatments such as surgery, transarterial chemoembolization (TACE) and high intensity focus ultrasound treatment would influence the manifestation of TCM syndromes. Herbs with traditional efficacy of tonifying Qi, blood and Yin, soothing liver-Qi stagnation, clearing heat and detoxifying and dissolving stasis, have been demonstrated to be potent to prevent hepatocarcinogenesis. TCM has been widely used in all aspects of integrative therapy in hepatocarcinoma, including surgical resection, liver transplantation, TACE, local ablative therapies and even as monotherapy for middle-advanced stage hepatocarcinoma. Clinical practices have confirmed that TCM is effective to alleviate clinical symptoms, improve quality of life and immune function, prevent recurrence and metastasis, delay tumor progression, and prolong survival time in hepatocarcinoma patients. The effective mechanism of TCM against hepatocarcinoma is related to inducing apoptosis, autophagy, anoikis and cell senescence, arresting cell cycle, regulating immune function, inhibiting metastasis and angiogenesis, reversing drug resistance and enhancing effects of chemotherapy. Along with the progress of research in this field, TCM will contribute more to the prevention and treatment of hepatocarcinoma. AbstractTraditional Chinese medicine (TCM) has played a positive role in the management of hepatocarcinoma. Hepatocarcinoma patients may present Qi-stagnation, damp-heat, blood stasis, Qi-deficiency, Yin-deficiency REVIEWSubmit a

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“…Previous study demonstrated that bufalin inhibited the proliferation of SMMC-7721 and HepG2 human hepatocellular carcinoma cell lines in a dose-dependent and time-dependent manner and therefore would induce G2/M phase cell cycle arrest,21 induce the proteins for the mitochondria-mediated apoptosis,22 and inhibit the AKT/GSK3 beta/beta-catenin/E-cadherin signaling pathway 11…”

Section: Discussionmentioning

confidence: 99%

Radiosynthesis and pharmacokinetics of [<sup>18</sup>F]fluoroethyl bufalin in hepatocellular carcinoma-bearing mice

Yang¹,

Liu²,

Huang³

et al. 2017

OTT

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PurposeBufalin, the main component of a Chinese traditional medicine chansu, shows convincing anticancer effects in a lot of tumor cell lines. However, its in vivo behavior is still unclear. This research aimed to evaluate how bufalin was dynamically absorbed after intravenous injection in animal models. We developed a radiosynthesis method of [18F]fluoroethyl bufalin to noninvasively evaluate the tissue biodistribution and pharmacokinetics in hepatocellular carcinoma-bearing mice.Methods[18F]fluoroethyl bufalin was synthesized with conjugation of 18F-CH2CH2OTs and bufalin. The radiochemical purity was proved by the radio-high-performance liquid chromatography (HPLC). The pharmacokinetic studies of [18F]fluoroethyl bufalin were then performed in Institute of Cancer Research (ICR) mice. Furthermore, the biodistribution and metabolism of [18F]fluoroethyl bufalin in HepG2 and SMMC-7721 tumor-bearing nude mice were studied in vivo by micro-positron emission tomography (micro-PET).ResultsThe radiochemical purity (RCP) of [18F]fluoroethyl bufalin confirmed by radio-HPLC was 99%±0.18%, and [18F]fluoroethyl bufalin showed good in vitro and in vivo stabilities. Blood dynamics of [18F]fluoroethyl bufalin conformed to the two compartments in the ICR mice model. The pharmacokinetic parameters of [18F]fluoroethyl bufalin were calculated by DAS 2.0 software. The area under concentration–time curve (AUC0–t) and the values of clearance (CL) were 540.137 μg/L·min and 0.001 L/min/kg, respectively. The half-life of distribution (t1/2α) and half-life of elimination (t1/2β) were 0.693 and 510.223 min, respectively. Micro-PET imaging showed that [18F]fluoroethyl bufalin was quickly distributed via the blood circulation; the major tissue biodistribution of [18F]fluoroethyl bufalin in HepG2 and SMMC-7721 tumor-bearing mice was liver and bladder.Conclusion[18F]fluoroethyl bufalin was accumulated rapidly in the liver at an early time point (5 min) post injection (pi) and then declined slowly, mainly through both the hepatic pathway and the renal pathway. Our study showed the biodistribution of [18F]fluoroethyl bufalin in micro-PET images and provided visible information for demonstrating the bioactivities of bufalin.

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Bufothionine, a possible effective component in cinobufocini injection for hepatocellular carcinoma

Cited by 39 publications

References 8 publications

Chinese herb cinobufagin-reduced cancer pain is associated with increased peripheral opioids by invaded CD3/4/8 lymphocytes

Chinese herb cinobufagin-reduced cancer pain is associated with increased peripheral opioids by invaded CD3/4/8 lymphocytes

Traditional Chinese medicine for prevention and treatment of hepatocarcinoma: From bench to bedside

Radiosynthesis and pharmacokinetics of [<sup>18</sup>F]fluoroethyl bufalin in hepatocellular carcinoma-bearing mice

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