Bufalin enhances antitumor effect of paclitaxel on cervical tumorigenesis via inhibiting the integrin α2/β5/FAK signaling pathway

Liu, Fei; Tong, Duo; Li, Haoran; Liu, Mingming; Li, Jiajia; Wang, Ziliang; Cheng, Xi

doi:10.18632/oncotarget.6840

Cited by 37 publications

(30 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Bufalin is a kind of cardiac glycosides which is derived from the serous fluid secreted by the parotid venom glands and skin of Bufo melanostictus and Bufo bufo gargarizans [20]. Researches have showed that Bufalin has many pharmacological activities, including anti-inflammatory, anti-tumor, antiviral, cardiotonic and narcotic effects [21][22][23][24].…”

Section: Discussionmentioning

confidence: 99%

Anti-tumor Activity of Bufalin by Inhibiting c-MET Mediated MEK/ERK and PI3K/AKT Signaling Pathways in Gallbladder Cancer

Qian¹,

Su²,

Wang³

et al. 2020

J. Cancer

View full text Add to dashboard Cite

Gallbladder cancer is one of the most common malignant tumors in the biliary tract. In recent years, the chemotherapy treatment for gallbladder carcinoma has exhibited obvious characteristics of drug resistance and insensitivity, and one of the main factors is the existence of cancer stem cells. Here in this study, the effect of Bufalin on gallbladder cancer (GBC-SD) cells and the related mechanism were studied. The results indicated that Bufalin could inhibit the growth of gallbladder carcinoma both in vivo and in vitro. According to the biological behavior analysis, Bufalin induced apoptosis, inhibited the propagation, migration and invasion of GBC-SD cells, and blocked cell cycle at the G2/M stage. Besides, Bufalin inhibited the tumor sphere formation capability of gallbladder carcinoma in matrigel, reduced the expression of multiple stemness-associated proteins, including Oct4, Sox2 and the stem cell-surface marker proteins CD133 and CD44. Western blot assay showed that Bufalin inhibited MEK/ERK and PI3-K/AKT signaling pathways by inhibiting the expression of p-c-Met, which in turn affected the expression of apoptosis-related protein Mcl-1, and the invasion-associated proteins E-cadherin, MMP9 and Snail. Bufalin was found to have an inhibitory effect on the GBC-SD cell growth and reduce the self-renewal and characteristic of gallbladder cancer stem cells. It enhanced the chemotherapeutic sensitivity and reduced the metastasis of gallbladder carcinoma. In conclusion, Bufalin can be used as a new promising anticancer drug for gallbladder cancer patients who are resistant to traditional chemotherapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Anti-tumor Activity of Bufalin by Inhibiting c-MET Mediated MEK/ERK and PI3K/AKT Signaling Pathways in Gallbladder Cancer

Qian¹,

Su²,

Wang³

et al. 2020

J. Cancer

View full text Add to dashboard Cite

show abstract

“…PI3K pathway plays an important role in regulating cell survival, angiogenesis, cell invasion, and metastasis [ 32 ]. Liu et al reported that integrin α2/FAK/AKT1/ GSK3β signaling was involved in cell cycle regulation of bufalin in cervical cancer [ 33 ]. However, the link between PI3K and Aurora kinase has been limitedly described as well as the mechanism by which PI3K regulates mitotic kinase is still poorly understood.…”

Section: Discussionmentioning

confidence: 99%

Cardiac glycoside bufalin blocks cancer cell growth by inhibition of Aurora A and Aurora B activation via PI3K-Akt pathway

Xie

Lin

et al. 2018

Oncotarget

View full text Add to dashboard Cite

In our previous study, cardiac glycosides including bufalin, a group of sodium pump (Na+/K+-ATPase) inhibitors widely used to treat heart failure for many years, have been demonstrated to induce a delay of mitotic entry and mitotic arrest in many cancer cells. However, the underlying mechanism remains poorly understood. Here, we reported for the first time that cardiac glycoside bufalin induced mitotic entry delay and prometaphase arrest by inhibition of activation of Aurora A/B. Furthermore, cardiac glycoside bufalin prevented Aurora A recruitment to mitotic centrosomes and Aurora B recruitment to unattached kinetochores. Mechanistically, bufalin and knockdown of sodium pump inhibited PI3K-Akt pathway, which in turn inhibit the activation of Aurora A/B, followed by a delay in mitotic entry and mitotic arrest. These actions were reversed by overexpression of Akt. In addition, ERK, mTOR, and ROS are not involved in bufalin-mediated downregulation of active form of Aurora A/B. Taken together, cardiac glycoside bufalin induces mitotic entry delay and mitotic arrest in cancer cells through inhibition of Aurora A/B activation via PI3K-Akt pathway. Based on this novel finding we could suggest that targeting PI3K-Akt pathway may have therapeutic value for the treatment of cancers associated with sodium pump overexpression.

show abstract

“…Modern research has found BU to have strong anti-tumour effects. Its mechanism involves the inhibition of tumour cell growth and the induction of apoptosis of tumour cells[ 28 , 29 ]. This paper reports, for the first time, an investigation of the function and mechanism of BU in reversing ABCB1-mediated MDR.…”

Section: Discussionmentioning

confidence: 99%

Bufalin reverses ABCB1-mediated drug resistance in colorectal cancer

et al. 2017

View full text Add to dashboard Cite

Multidrug resistance (MDR), mainly mediated by ABCB1 transporter, is a major cause for chemotherapy failure. Bufalin (BU), an active component of the traditional Chinese medicine chan’su, has been reported to have antitumor effects on various types of cancer cells. The purpose of this present study was to investigate the reversal effect of BU on ABCB1-mediated multidrug resistance in colorectal cancer. BU at safe concentration (5, 10, 20 nM) could reverse chemosensitivity of ABCB1-overexpression HCT8/ADR, LoVo/ADR and HCT8/ABCB1 nearly back to their parental cells level. In addition, results from the drug accumulation studies revealed that BU was able to enhance intracellular accumulation of doxorubicin (DOX) and Rhodamine 123 (Rho-123) in a dose-dependent manner. Furthermore, Western blot assays showed that BU significantly inhibited the expression level of ABCB1 protein. Meanwhile, BU stimulated the ATPase activity of ABCB1, which suggested that BU might be a substrate of ABCB1. More interestingly, docking analysis predicted that BU could be docked into the large hydrophobic drug-binding cavity of human ABCB1. Importantly, BU remarkable increased the effect of DOX against the ABCB1 resistant HCT8/ADR colorectal cell xenografts in nude mice, without inducing any obvious toxicity. Overall, we concluded that BU efficiently reversed ABCB1-mediated MDR through not only inhibited the efflux function of ABCB1, but also down-regulate its protein expression, which might represent a potential and superior ABCB1 modulator in colorectal cancer.

show abstract

Bufalin enhances antitumor effect of paclitaxel on cervical tumorigenesis via inhibiting the integrin α2/β5/FAK signaling pathway

Cited by 37 publications

References 34 publications

Anti-tumor Activity of Bufalin by Inhibiting c-MET Mediated MEK/ERK and PI3K/AKT Signaling Pathways in Gallbladder Cancer

Anti-tumor Activity of Bufalin by Inhibiting c-MET Mediated MEK/ERK and PI3K/AKT Signaling Pathways in Gallbladder Cancer

Cardiac glycoside bufalin blocks cancer cell growth by inhibition of Aurora A and Aurora B activation via PI3K-Akt pathway

Bufalin reverses ABCB1-mediated drug resistance in colorectal cancer

Contact Info

Product

Resources

About