Canagliflozin inhibits p-gp function and early autophagy and improves the sensitivity to the antitumor effect of doxorubicin

Zhong, Jin; Sun, Pengbo; Xu, Ning; Liao, Meijian; Xu, Chenke; Ding, Yipei; Cai, Jun; Zhang, Yaou; Xie, Weidong

doi:10.1016/j.bcp.2020.113856

Cited by 30 publications

(23 citation statements)

References 22 publications

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“…It seems that enhancing expression of oncosuppressor miRNAs such as miRNA-124 [86] and miRNA-223 [87] is of importance in impairing cancer proliferation and migration, and increasing their sensitivity into DOX chemotherapy. Furthermore, reducing activity of drug transporters such as P-gp elevates DOX accumulation in cancer cells and is of importance in reversing chemoresistance [88]. Overall, studies are in agreement with the fact that different molecular pathways and mechanisms can involve in inducing DOX chemoresistance and phytochemical are potential agents in triggering chemosensitivity [89][90][91][92].…”

Section: Doxorubicin: Cancer Resistance and Side Effectssupporting

confidence: 69%

Polychemotherapy with Curcumin and Doxorubicin via Biological Nanoplatforms: Enhancing Antitumor Activity

et al. 2020

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Doxorubicin (DOX) is a well-known chemotherapeutic agent extensively applied in the field of cancer therapy. However, similar to other chemotherapeutic agents such as cisplatin, paclitaxel, docetaxel, etoposide and oxaliplatin, cancer cells are able to obtain chemoresistance that limits DOX efficacy. In respect to dose-dependent side effect of DOX, enhancing its dosage is not recommended for effective cancer chemotherapy. Therefore, different strategies have been considered for reversing DOX resistance and diminishing its side effects. Phytochemical are potential candidates in this case due to their great pharmacological activities. Curcumin is a potential antitumor phytochemical isolated from Curcuma longa with capacity of suppressing cancer metastasis and proliferation and affecting molecular pathways. Experiments have demonstrated the potential of curcumin for inhibiting chemoresistance by downregulating oncogene pathways such as MMP-2, TGF-β, EMT, PI3K/Akt, NF-κB and AP-1. Furthermore, coadministration of curcumin and DOX potentiates apoptosis induction in cancer cells. In light of this, nanoplatforms have been employed for codelivery of curcumin and DOX. This results in promoting the bioavailability and internalization of the aforementioned active compounds in cancer cells and, consequently, enhancing their antitumor activity. Noteworthy, curcumin has been applied for reducing adverse effects of DOX on normal cells and tissues via reducing inflammation, oxidative stress and apoptosis. The current review highlights the anticancer mechanism, side effects and codelivery of curcumin and DOX via nanovehicles.

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Section: Doxorubicin: Cancer Resistance and Side Effectssupporting

confidence: 69%

Polychemotherapy with Curcumin and Doxorubicin via Biological Nanoplatforms: Enhancing Antitumor Activity

et al. 2020

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“…CAN inhibited energy metabolism by targeting mitochondrial complex 1 (Secker et al, 2018), in an off-target manner, which was independent of the SGLT2 receptor. In our previous studies, CAN significantly inhibited intracellular glucose metabolism (Xu et al, 2018;Zhong et al, 2020). These phenomena might partly explain why CAN inhibited ROS production, as observed in this study.…”

Section: Discussionsupporting

confidence: 83%

Canagliflozin attenuates lipotoxicity in cardiomyocytes and protects diabetic mouse hearts by inhibiting the mTOR/HIF-1α pathway

et al. 2021

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“…CAN inhibited energy metabolism by targeting mitochondrial complex 1 (41), in an off-target manner, which was independent of the SGLT2 receptor. In our previous studies, CAN signi cantly inhibited intracellular glucose metabolism (13,42). These phenomena might partly explain why CAN inhibited ROS production, as observed in this study.…”

Section: Discussionsupporting

confidence: 81%

Canagliflozin Attenuates Lipotoxicity in Cardiomyocytes and Protects Diabetic Mouse Hearts by Targeting the mTOR/HIF-1α Pathway

Sun

Ding

Luo

et al. 2020

Preprint

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BackgroundLipotoxicity plays an important role in the development of diabetic cardiomyopathy and heart failure (HF). Canagliflozin (CAN), a marketed sodium-glucose co-transporter 2 inhibitor, has significant beneficial effects on HF. However, the potential pharmacological mechanism is still unknown.MethodsIn this study, we evaluated the protective effects and mechanism of CAN in the hearts of a C57BL/6J diabetic mouse model induced by a high-fat diet/streptozotocin (HFD/STZ) for 12 weeks in vivo and using HL-1 cells (a type of mouse cardiomyocyte line) induced by palmitic acid (PA) in vitro.ResultsCAN could significantly alleviate lipid accumulation and inflammatory responses in the hearts of the HFD/STZ-induced diabetic mice. Furthermore, CAN significantly attenuated the inflammatory injury induced by PA in the HL-1 cells. In addition, CAN bound to the mammalian target of rapamycin (mTOR) and significantly inhibited mTOR phosphorylation and hypoxia inducible factor-1α (HIF-1α) expression.ConclusionCAN attenuated lipotoxicity in cardiomyocytes and protected diabetic mouse hearts by targeting the mTOR/HIF-1α pathway.

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Canagliflozin inhibits p-gp function and early autophagy and improves the sensitivity to the antitumor effect of doxorubicin

Cited by 30 publications

References 22 publications

Polychemotherapy with Curcumin and Doxorubicin via Biological Nanoplatforms: Enhancing Antitumor Activity

Polychemotherapy with Curcumin and Doxorubicin via Biological Nanoplatforms: Enhancing Antitumor Activity

Canagliflozin attenuates lipotoxicity in cardiomyocytes and protects diabetic mouse hearts by inhibiting the mTOR/HIF-1α pathway

Canagliflozin Attenuates Lipotoxicity in Cardiomyocytes and Protects Diabetic Mouse Hearts by Targeting the mTOR/HIF-1α Pathway

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