Salvianolic Acid B Prevents Arsenic Trioxide-Induced CardiotoxicityIn Vivoand Enhances Its Anticancer ActivityIn Vitro

Abstract

Clinical attempts to reduce the cardiotoxicity of arsenic trioxide (ATO) without compromising its anticancer activities remain to be an unresolved issue. In this study, we determined whether Sal B can protect against ATO-induced cardiac toxicity in vivo and increase the toxicity of ATO toward cancer cells. Combination treatment of Sal B and ATO was investigated using BALB/c mice and human hepatoma (HepG2) cells and human cervical cancer (HeLa) cells. The results showed that the combination treatment significantly improved the ATO-induced loss of cardiac function, attenuated damage of cardiomyocytic structure, and suppressed the ATO-induced release of cardiac enzymes into serum in BALB/c mouse models. The expression levels of Bcl-2 and p-Akt in the mice treated with ATO alone were reduced, whereas those in the mice given the combination treatment were similar to those in the control mice. Moreover, the combination treatment significantly enhanced the ATO-induced cytotoxicity and apoptosis of HepG2 cells and HeLa cells. Increases in apoptotic marker cleaved poly (ADP-ribose) polymerase and decreases in procaspase-3 expressions were observed through western blot. Taken together, these observations indicate that the combination treatment of Sal B and ATO is potentially applicable for treating cancer with reduced cardiotoxic side effects.

Calcium homeostasis and endoplasmic reticulum stress are involved in Salvianolic acid B-offered protection against cardiac toxicity of arsenic trioxide

“…Our results also implicated ER stress-associated apoptosis inhibition in the Sal B cardioprotective mechanism. Combined with our previous report [ 19 , 20 ], our findings demonstrated that Sal B protects against ATO-induced cardiotoxicity not only through its anti-oxidative and anti-apoptotic capacities, but also by modulating calcium homeostasis and suppressing ER stress.…”

“…All animal care procedures and interventions were performed in accordance with the Guidelines and Policies for Animal Surgery provided by the Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, and were approved by the Institutional Animal Use and Care Committee (registration number: #IMPLAD2015090216). Experimental protocols were previously described [ 20 ]. In brief, rats were randomly divided into four groups (n=15/group): (I) the control group (10 mL/kg saline), (II) Sal B-treated group (2 mg/kg Sal B), (III) ATO-treated group (1 mg/kg ATO), and (IV) ATO + Sal B group (2 mg/kg Sal B 1 h before ATO administration).…”

“…Our previous studies showed that Sal B attenuates ATO-induced cardiac injury via PI3K/Akt signaling in H9c2 cells [ 19 ]. Sal B also alleviates ATO-induced loss of cardiac function and damage to cardiomyocytic structures in BALB/c mice, and can improve ATO-induced cytotoxicity and apoptosis in HepG2 and HeLa cells [ 20 ]. These data suggest that Sal B and ATO act synergistically, with reduced cardiovascular damage.…”

Salvianolic acid B reverses multidrug resistance in HCT-8/VCR human colorectal cancer cells by increasing ROS levels

“…Its role in reversing tumor MDR has attracted increasing attention (10,11). In the present study, SalB was used to treat the MDR colorectal cancer cell line HCT-8/VCR, and explore its effect on drug resistance.…”

Ionic liquid and aqueous two‐phase extraction based on salting‐out coupled with high‐performance liquid chromatography for the determination of seven rare ginsenosides in Xue‐Sai‐Tong injection

“…Many results showed that ginsenoside 20(S)-Rg 3 might provide neuroprotection against the cerebral ischemia-induced injury in rat brain through reducing lipid peroxides, scavenging free radicals and improving the energy metabolism [5]; ginsenoside 20(R)-Rg 3 could attenuate the neuronal apoptosis caused by cerebral ischemiareperfusion injury [6]; ginsenoside Rk 3 had been reported to exert cardio protective effects against hypoxia/reoxygenation (H/R) injury [7]; ginsenosides 20(S)-Rg 3 and 20(S)-Rh 2 had the potential to induce cell detachment and inhibit the proliferation of prostate cancer cells [8]; ginsenoside Rg 5 could induce apoptosis and DNA damage in human cervical cancer cells [9]; ginsenoside Rk 1 had the capability to inhibit telomerase activity and induce apoptosis in human hepatocellular carcinoma cells [10]; and ginsenoside F 4 and ginsenoside Rg 6 had the ability of inhibitory and apoptosis-inducing effect on (GF4) human lymphocytoma Jurkat (JK) cell [11,12]. Therefore, the rare ginsenosides plays an important role in the function of Xue-Sai-Tong injection.…”