Abstract
Cancer is the leading cause of deaths around the world, especially in low- and middle- income countries. Pirarubicin (THP) is an effective drug for treatment of cancer, however, there still exists cardiotoxic effects of THP. Rutin is a kind of antioxidative compound extracted from plants, and might be a protective compound for cardiomyocytes. Phosphatidylinositol 3-hydroxy kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway is critical for cellular survival, proliferation and metabolism, and thus we speculated rutin might perform a protective role in cardiomyocytes via PI3K/AKT/mTOR signaling pathway. And in this experiment, we first established a cardiotoxicity model of THP in mice model and cell models, and then found that rutin treatment could increase the proliferation of cells at low concentration. Then we explored the possible mechanism of the protective effect of rutin using Western blotting, quantitative polymerase chain reaction (qPCR) and ELISA methods, and found that the activation of PI3K/AKT/mTOR/nuclear factor-κB (NF-κB) signaling pathway was increased, and expression of downstream molecules involved in antioxidative stress were also increased. We further noticed that concentration of angiogenesis promoting factors were also increased in medium of cultured cells. Thus, we speculated that rutin could increase the activation of PI3K/AKT/mTOR signaling pathway, further decrease the oxidative stress level via increasing the expression of antioxidative stress enzymes with the increasing concentration of angiogenesis promoting factors, resulting in the protective role in cardiomyocytes and cardiac function.
Highlights
The mortality of cancer has been growing widely, and new cancer cases have been reported to increase to 19.3 million in 2025
Compared with treatment group (TP) group, the LVFS% and LVEF% was significantly increased in blank control group (NC) and THP treatment with low-dose rutin group (TL) group (P
Microenvironment is related to integrins and focal adhesion kinases (FAKs), membrane protrusions and degradation of extracellular matrix (ECM) is closely related to the invasion, epithelial–mesenchymal transition (EMT), and metastasis of cancer cells [13,14]
Summary
The mortality of cancer has been growing widely, and new cancer cases have been reported to increase to 19.3 million in 2025. Treatments for cancer nowadays include surgery, radiotherapy, cytotoxic chemotherapy, hormonal therapy, immunotherapy, and targeted therapies [2]. The effect of these treatments is still limited. Pirarubicin (THP) is a new anthracycline anticancer drug which could generate cell cycle. THP alone or combined with other anticancer drugs based on THP has been proven as an effective treatment for HCC and other cancers, and presented lower cardio toxicity, faster cellular uptake, and plasma clearance [3]. THP and other low-molecular weight anticancer drugs could lead to severe side effects. Rutin is a flavonol glycoside composed of quercetin and disaccharide rutinose, which is produced by consumption including buckwheat groats, vegetables, and fruits. Previous studies found that rutin performed multiple pharmacological functions including antioxidant, anticarcinogenic
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