Tetrandrine antagonizes acute megakaryoblastic leukaemia growth by forcing autophagy‐mediated differentiation

Liu, Ting; Zhang, Zhenxing; Yu, Chunjie; Chen, Zeng; Xu, Xiaoqing; Wu, Guixian; Huang, Zan; Li, Wenhua

doi:10.1111/bph.14031

Cited by 34 publications

(28 citation statements)

References 57 publications

(57 reference statements)

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“…Many monomers extracted from traditional Chinese medicine have inhibitory effects on osteoclastogenesis (Chen et al, 2017). Tetrandrine, a bis-benzylisoquinoline alkaloid isolated from Stephania tetrandra S Moore and other Chinese herbs, has been shown to have anti-inflammatory, antineoplastic, immunologic, and antiallergenic effects (Mei et al, 2015;Liu et al, 2017;Yu et al, 2018;Jia et al, 2019). Clinically, it has been widely used in the treatment of rheumatoid arthritis.…”

Section: Discussionmentioning

confidence: 99%

“…Tetrandrine, a bis-benzylisoquinoline alkaloid, has been isolated from Stephania tetrandra S Moore, and other Chinese herbs. Previous studies have demonstrated that tetrandrine has antiinflammatory, antineoplastic, immunologic, and antiallergenic effects, and it has been widely used clinically in the treatment of rheumatoid arthritis (Wang et al, 2004;Liu et al, 2017;Yu et al, 2018). PMOP has a strong correlation with rheumatoid arthritis considering inflammatory cytokines played key roles in both of them.…”

Section: Introductionmentioning

confidence: 99%

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Tetrandrine Prevents Bone Loss in Ovariectomized Mice by Inhibiting RANKL-Induced Osteoclastogenesis

et al. 2020

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Postmenopausal osteoporosis (PMOP) is a metabolic bone disease characterized by decreased bone density and strength due to the imbalance between osteogenesis and osteoclastogenesis. Postmenopausal estrogen withdrawal increases proinflammatory cytokines and increases the serum level of Receptor activator of NF-kB ligand (RANKL)/Osteoprotegerin (OPG), which then leads to the overactivation of osteoclastogenesis. Tetrandrine, a bis-benzylisoquinoline alkaloid, has been widely used in the treatment of rheumatoid arthritis clinically in China. Here, we demonstrate that tetrandrine significantly prevented ovariectomy-induced bone loss and inhibited RANKL-induced osteoclastogenesis. In vivo, we found that intraperitoneal injection of tetrandrine (30 mg/kg) every other day markedly reduced bone loss in ovariectomized mice and the serum levels of TRAcp5b, TNF-a, IL-6, CTX-I, and RANKL/OPG were significantly decreased. In vitro, we found that tetrandrine significantly inhibited osteoclast differentiation in bone marrow monocytes (BMMs) and RAW264.7 cells according to the results of osteoclastogenesis-related gene expression, tartrate-resistant acid phosphatase (TRAP) staining and actin-ring formation as well as bone resorption assay. Mechanistically, tetrandrine inhibited RANKL-induced osteoclastogenesis by suppressing NF-kB, Ca2 + , PI3K/AKT, and MAPKs signaling pathways. Taken together, our findings suggest that tetrandrine suppresses osteoclastogenesis through modulation of multiple pathways and has potential value as a therapeutic agent for PMOP, especially for those suffering from RA and PMOP at the same time.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Tetrandrine Prevents Bone Loss in Ovariectomized Mice by Inhibiting RANKL-Induced Osteoclastogenesis

et al. 2020

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“…Tetrandrine has broad-spectrum antitumor effects (Bhagya and Chandrashekar 2018;Liu 2017;Liu et al 2016) in many types of cancer cells, including human liver cancer (Zhang et al 2018a;Yu and Ho 2013), osteosarcoma Lu et al 2017), oral cancer (Lien et al 2017;Huang et al 2013), colon carcinoma (Meng et al 2004;Li et al 2019), gastric cancer (Bai et al 2018;Qin et al 2013), brain glioblastoma multiforme GBM 8401 cancer (Jiang et al 2019) and lung carcinoma (Chow et al 2018;Cho et al 2009). It also exhibits antineoplastic activity against gallbladder carcinoma (Zhu et al 2014), thyroid carcinoma B-CPAP cells ), prostatic carcinoma PC3 cells (Lan et al 2018), esophageal cancer , breast cancer (Guo and Pei 2019), pancreatic cancer (Singh et al 2018), nasopharyngeal carcinoma (Lin et al 2016(Lin et al , 2017b, acute megakaryoblastic leukemia (Liu et al 2017c), cervical cancer (Zhang et al 2018b) and renal carcinoma (Chen et al 2014(Chen et al , 2017a cells. Although tetrandrine exhibited broad anti-tumor effects, a number of these studies lacked positive controls or anti-tumor evaluation of tetrandrine in vivo.…”

Section: Anti-inflammatory Effectsmentioning

confidence: 99%

A critical review: traditional uses, phytochemistry, pharmacology and toxicology of Stephania tetrandra S. Moore (Fen Fang Ji)

2020

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Stephania tetrandra S. Moore (S. tetrandra) is distributed widely in tropical and subtropical regions of Asia and Africa. The root of this plant is known in Chinese as ''Fen Fang Ji''. It is commonly used in traditional Chinese medicine to treat arthralgia caused by rheumatism, wet beriberi, dysuria, eczema and inflamed sores. Although promising reports have been published on the various chemical constituents and activities of S. tetrandra, no review comprehensively summarizes its traditional uses, phytochemistry, pharmacology and toxicology. Therefore, the review aims to provide a critical and comprehensive evaluation of the traditional use, phytochemistry, pharmacological properties, pharmacokinetics and toxicology of S. tetrandra in China, and meaningful guidelines for future investigations.

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“…Our previous studies have indicated that tetrandrine induced apoptosis at a high concentration and induced autophagy at low concentrations [ 10 – 12 ]. Moreover, tetrandrine showed potential anti-tumor activity in leukemia and hepatocellular carcinoma [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Combination therapy with protein kinase inhibitor H89 and Tetrandrine elicits enhanced synergistic antitumor efficacy

Liu

Chen

et al. 2018

J Exp Clin Cancer Res

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BackgroundTetrandrine, a bisbenzylisoquinoline alkaloid that was isolated from the medicinal plant Stephania tetrandrine S. Moore, was recently identified as a novel chemotherapy drug. Tetrandrine exhibited a potential antitumor effect on multiple types of cancer. Notably, an enhanced therapeutic efficacy was identified when tetrandrine was combined with a molecularly targeted agent. H89 is a potent inhibitor of protein kinase A and is an isoquinoline sulfonamide.MethodsThe effects of H89 combined with tetrandrine were investigated in vitro with respect to cell viability, apoptosis and autophagy, and synergy was assessed by calculation of the combination index. The mechanism was examined by western blot, flow cytometry and fluorescence microscopy. This combination was also evaluated in a mouse xenograft model; tumor growth and tumor lysates were analyzed, and a TUNEL assay was performed.ResultsCombined treatment with H89 and tetrandrine exerts a mostly synergistic anti-tumor effect on human cancer cells in vitro and in vivo while sparing normal cells. Mechanistically, the combined therapy significantly induced cancer cell apoptosis and autophagy, which were mediated by ROS regulated PKA and ERK signaling. Moreover, Mcl-1 and c-Myc were shown to play a critical role in H89/tetrandrine combined treatment. Mcl-1 ectopic expression significantly diminished H89/tetrandrine sensitivity and amplified c-Myc sensitized cancer cells in the combined treatment.ConclusionOur findings demonstrate that the combination of tetrandrine and H89 exhibits an enhanced therapeutic effect and may become a promising therapeutic strategy for cancer patients. They also indicate a significant clinical application of tetrandrine in the treatment of human cancer. Moreover, the combination of H89/tetrandrine provides new selectively targeted therapeutic strategies for patients with c-Myc amplification.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0779-2) contains supplementary material, which is available to authorized users.

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Tetrandrine antagonizes acute megakaryoblastic leukaemia growth by forcing autophagy‐mediated differentiation

Abstract: Modulating autophagy-mediated differentiation may be a novel strategy for treating AMKL, and tetrandrine has the potential to be developed as a differentiation-inducing agent for AMKL chemotherapy.

Cited by 34 publications

References 57 publications

Tetrandrine Prevents Bone Loss in Ovariectomized Mice by Inhibiting RANKL-Induced Osteoclastogenesis

Tetrandrine Prevents Bone Loss in Ovariectomized Mice by Inhibiting RANKL-Induced Osteoclastogenesis

A critical review: traditional uses, phytochemistry, pharmacology and toxicology of Stephania tetrandra S. Moore (Fen Fang Ji)

Combination therapy with protein kinase inhibitor H89 and Tetrandrine elicits enhanced synergistic antitumor efficacy

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