Harringtonine injection for the treatment of castration-resistant prostate cancer after second-line treatment, a prospective single-arm, open-label clinical study

Start Date01 Jun 2023

Sponsor / Collaborator

Southeast University Affiliated Zhonda Hospital

100 Clinical Results associated with Harringtonine

100 Translational Medicine associated with Harringtonine

100 Patents (Medical) associated with Harringtonine

1,500

Literatures (Medical) associated with Harringtonine

31 Dec 2024·Bioengineered

Establishment and characterization of a highly metastatic hepatocellular carcinoma cell line

Article

Author: Zhang, Yu ; Huang, Jiacheng ; Wang, Menglan ; Yu, Anning ; Hu, Zhenhua ; Bu, Chiwen ; Sun, Mengqing ; Qiao, Yiting ; Zhou, Jie ; Zheng, Huilin

The prevalence of alcohol-related hepatocellular carcinoma (HCC) has been increasing during the last decade. Cancer research requires cell lines suitable for both in vitro and in vivo assays. However, there is a lack of cell lines with a high in vivo metastatic capacity for this HCC subtype. Herein, a new HCC cell line was established, named HCC-ZJ, using cells from a patient diagnosed with alcohol-related HCC. The karyotype of HCC-ZJ was 46, XY, del (p11.2). Whole-exome sequencing identified several genetic variations in HCC-Z that occur frequently in alcohol-associated HCC, such as mutations in TERT, CTNNB1, ARID1A, CDKN2A, SMARCA2, and HGF. Cell counting kit-8 assays, colony formation assays, and Transwell assays were performed to evaluate the proliferation, migration, and sensitivity to sorafenib and lenvatinib of HCC-Z in vitro. HCC-ZJ showed a robust proliferation rate, a weak foci-forming ability, a strong migration capacity, and a moderate invasion tendency in vitro. Finally, the tumorigenicity and metastatic capacity of HCC-Z were evaluated using a subcutaneous xenograft model, an orthotopic xenograft model, and a tail-veil injection model. HCCZJ exhibited strong tumorigenicity in the subcutaneous xenograft and orthotopic tumor models. Moreover, HCC-ZJ spontaneously formed pulmonary metastases in the orthotopic tumor model. In summary, a new HCC cell line derived from a patient with alcohol-related HCC was established, which showed a high metastatic capacity and could be applied for in vitro and in vivo experiments during pre-clinical research.Highlights• An alcohol-related HCC cell line, HCC-ZJ, was established• HCC-ZJ was applicable for in vitro functional experiment and gene editing• HCC-ZJ was applicable for in vivo tumor growth and spontaneous metastasis models.

01 Nov 2024·Heliyon

Zuogui Jiangtang Jieyu prescription improves diabetes-related depression by modulation of gut microbiota and neuroinflammation in hippocampus

Article

Author: Hui, Yang ; Hongping, Long ; Wei, Li ; Jian, Liu ; Lin, Liu ; Shihui, Lei ; Jinxi, Wang

ContextThere is a significant challenge associated with the co-morbidity of mental and physical illnesses throughout the world. A classic example of mental/physical co-morbidity is diabetes-related depression (DD).ObjectiveDD is treated with Zuogui Jiangtang Jieyu prescription (ZJJ). Diabetes and psychiatric disorders are associated with dysbiosis of the gut microbiota. In this study, the aim is to examine the effects of ZJJ on gut microbiota and neuroinflammation in DD.MethodsA model of DD was established and treated with medium and high doses of ZJJ as well as Metformin & Fluoxetine. A detection of depressive-like behavior was then conducted on the rats. Proinflammatory cytokines were measured in cerebrospinal fluid, and HPA axis-related proteins, glucose metabolism, and lipopolysaccharide (LPS) were measured in serum. Fecal samples from each group were collected and analyzed by 16S rRNA sequencing; TLR4 and MyD88 levels were detected by Western blot and immunohistochemistry (IHC) in the hippocampus.ResultsHigh doses of ZJJ (ZJJ-H) were found to alleviate HPA axis hyperactivity and improve gut microbiota in rats with DD. Additionally, ZJJ treatment attenuated the inflammatory response in cerebrospinal fluid, e.g. a significant reduction in proinflammatory factors, a decrease in serum LPS levels, and an inhibition of TLR4/MyD88-related pathways in the hippocampus.Discussion and conclusionZJJ improved DD glucose metabolism and alleviated depression-like behaviors by improving gut microbiota and inhibiting hippocampal TLR4/Myd88 signaling pathways.

01 Nov 2024·European Journal of Pharmacology

Harringtonine metabolites: 5'-de-O-methylharringtonine and cephalotaxine, targeting spike protein and TMPRSS2 to double block membrane fusion of SARS-CoV-2 and its variants

Article

Author: He, Langchong ; Zhang, Yuxiu ; Gao, Jiapan ; Ma, Weina ; Ma, Xiaoyu ; Ren, Bingxi ; Lei, Panpan ; Hu, Shiling

Membrane fusion is the main pathway for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to invade host cells. Harringtonine (HT), derived from cephalotaxus fortunei Hook. f., has been recognized as an effective antagonist of SARS-CoV-2. It can directly block the active binding of spike (S) protein to host angiotensin converting enzyme 2 (ACE2), as well as hinder the enzymolysis of transmembrane serine proteases 2 (TMPRSS2). This study examined the potential of HT metabolites, 5'-de-O-methylharringtonine and cephalotaxine, as the membrane fusion inhibitors for SARS-CoV-2. 5'-De-O-methylharringtonine was synthesized and subsequently characterized by high resolution mass spectrometry and nuclear magnetic resonance to be structurally consistent, with a purity of 92.677% determined by reverse phase high performance liquid chromatography. Both 5'-de-O-methylharringtonine and cephalotaxine can specifically bind to SARS-CoV-2 S protein and TMPRSS2 using cell membrane chromatography. They can form hydrogen bonds with key sites that correlated highly with the enhanced binding affinity of SARS-CoV-2 and its variants to ACE2 or nafamostat to TMPRSS2. Moreover, 5'-de-O-methylharringtonine and cephalotaxine can inhibit pseudotyped virus entry and membrane fusion in a dose-dependent manner, with enhanced effectiveness upon elevated expression of TMPRSS2. Importantly, they displayed low cytotoxic effects on human normal cell lines. Our study suggested that 5'-de-O-methylharringtonine and cephalotaxine were of low toxicity and safety for humans as potential antagonists of SARS-CoV-2 and its variants, which deserve further validation in a biosafety level 3 facility.

100 Deals associated with Harringtonine

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Indication	Country/Location	Organization	Date
Acute Myeloid Leukemia	CN	Hainan Hotmed Tianya Pharmaceutical Co Ltd	-
Myelodysplastic Syndromes	CN	Hainan Hotmed Tianya Pharmaceutical Co Ltd	-
Philadelphia chromosome positive chronic myelogenous leukemia	CN	Hainan Hotmed Tianya Pharmaceutical Co Ltd	-
Polycythemia Vera	CN	Hainan Hotmed Tianya Pharmaceutical Co Ltd	-

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASCO2020	Not Applicable	Prostatic Cancer	18	Combination AA+HT+RT	(uslpfqsbpf) = ybzgzjdanw cfjjankihk (xmroxaboxt ) View more	Positive	25 May 2020
				HT+RT	(uslpfqsbpf) = sgyuertxlp cfjjankihk (xmroxaboxt ) View more
ASCO_GU2020	Not Applicable	Prostatic Cancer	13	Abiraterone acetate/Enzalutamide+RT	(yydrmizqdk) = qgjbxrzzca wkdgrjsrab (ucvcihrbzy )	Positive	19 Feb 2020
				HT+RT	(yydrmizqdk) = lpavqkxmej wkdgrjsrab (ucvcihrbzy )
ASCO2015	Not Applicable	Metastatic breast cancer	63	Everolimus and HT	(cbagulejsv) = lxvmvtvqdu apkzrlorxf (nhtncjuhdn )	-	20 May 2015

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