Salvianolic Acid B Slows the Progression of Breast Cancer Cell Growth via Enhancement of Apoptosis and Reduction of Oxidative Stress, Inflammation, and Angiogenesis

Abstract

Breast cancer is the current leading cause of cancer death in females worldwide. Although current chemotherapeutic drugs effectively reduce the progression of breast cancer, most of these drugs have many unwanted side effects. Salvianolic acid B (Sal-B) is a bioactive compound isolated from the root of Danshen Radix with potent antioxidant and anti-inflammatory properties. Since free radicals play a key role in the initiation and progression of tumor cells growth and enhance their metastatic potential, the current study was designed to investigate the antitumor activity of Sal-B and compare it with the antitumor activity of the traditional anticancer drug, cisplatin. In vitro, Sal-B decreased the human breast cancer adenocarcinoma (MCF-7) cells proliferation in a concentration and time dependent manner. In vivo and similar to cisplatin treatment, Sal-B significantly reduced tumor volume and increased the median survival when compared to tumor positive control mice group injected with Ehrlich solid carcinoma cell line (ESC). Sal-B decreased plasma level of malondialdehyde as a marker of oxidative stress and increased plasma level of reduced glutathione (GSH) as a marker of antioxidant defense when compared to control ESC injected mice. Either Sal-B or cisplatin treatment decreased tumor tissue levels of tumor necrosis factor (TNF-α), matrix metalloproteinase-8 (MMP-8), and Cyclin D1 in ESC treated mice. Contrary to cisplatin treatment, Sal-B did not decrease tumor tissue Ki-67 protein in ESC injected mice. Immunohistochemical analysis revealed that Sal-B or cisplatin treatment increased the expression of the apoptotic markers caspase-3 and P53. Although Sal-B or cisplatin significantly reduced the expression of the angiogenic factor vascular endothelial growth factor (VEGF) in ESC injected mice, only Sal-B reduced expression level of COX-2 in ESC injected mice. Our data suggest that Sal-B exhibits antitumor features against breast cancer cells possibly via enhancing apoptosis and reducing oxidative stress, inflammation, and angiogenesis.

Chemopreventive and anticancer activities of indomethacin and vitamin D combination on colorectal cancer induced by 1,2‑dimethylhydrazine in rats

“…On the other hand, its levels were increased in the indomethacin and vitamin D treatment group. These results are in harmony with the results reported by Jung et al ( 31 ), Okda et al ( 32 ) and Katary et al ( 33 ). The authors showed that caspase-3, which is a pro-apoptotic protein, was increased after the damage of hepatocellular carcinoma which occurred by CCl4, while its level was decreased due to the partial repairing occurred.…”

Inhibition of alpha-synuclein seeded fibril formation and toxicity by herbal medicinal extracts

“…Salvianolic acid B is considered the major watersoluble component of phenolic acids extracted from the dried root Salvia miltiorrhiza Bunge with a strong antioxidant, anti-inflammatory [17,18], and a significant anti-myocardial ischemia effect [19]. It has recently been reported that salvianolic acid B shows antitumor activity against breast cancer cells [20] and suspected to have potential effect on dementia [21]. Moreover, salvianolic acid B has a high concentration in the liver and a transporter known as OATP1B1 is involved in its hepatic uptake and clearance [22].…”

Use of zebrafish larvae lateral line to study protection against cisplatin-induced ototoxicity: A scoping review

“… 12 , 29 – 31 , 32 , 33 In addition, the embryos were also kept in E3 embryo media consisting of 5 mM NaCl, 0.17 mM KCl, 0.33 mM CaCl 2 , 0.33 MgSO 4 or in a standard bath solution containing: 120 mM NaCl, 2 mM KCl, 10 mM HEPES ( 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid ), 2 mM CaCl2 and 0.7 mM NaH2PO4 adjusted to pH 7.2. 21 , 34 For the anesthesia, MS-222 ( 3-aminobenzoic acid ethyl ester, methanesulfonate salt ) was used. Various sample size was used in the studies, ranging from 3 to 30 zebrafish per experimental group.…”

“… 20 , 21 , 23 – 25 , 30 The second experimental strategy used preconditioning with an otoprotective substance (quinoxaline, Z-LLF-CHO, benzamil, quinine, leupeptin, 3-MA, D-methionine, rapamycin, Sal B, SRT1720 and FUT-175) followed by simultaneous incubation with cisplatin. 12 , 19 , 31 , 34 , 38 The last experimental strategy consisted of preconditioning with otoprotective medication (dexmedetomidine, KR-22335, CHCP1, CHCP2, ATX) and later a sole exposure to cisplatin. 17 , 26 , 27 , 40 In one experimental protocol using adult zebrafish, a single microinjection of cisplatin and drug was applied, whereas when cell cultures were used, the experimental procedure included incubation with cisplatin and then co-incubation with the otoprotective substances.…”

“…Vlasits et al 12 0-100 µM 24 h Pre-treatment for 1 h, then co-exposure for 24 h Todd et al 5 0-1000 µM 4 h CIS exposure for 4 h Monroe et al 35 100 µM 45 min Co-exposure for 45 min Hong et al 24 1000 µM 4 h Co-exposure for 4 h Lee et al 23 1000 µM 4 h Co-exposure for 4 h Choi et al 42 1000 µM 6 h Co-exposure for 6 h Min et al 26 1000 µM 6 h Pre-treatment for 150 min, then CIS exposure for 6 h Niihori et al 6 1000 μM 4 h Pre-treatment for 12 h, then co-exposure for 4 h Monroe et al 33 100-500 µM 45 min CIS exposure for 45 min,regeneration for 3 h, then coexposure for 15 h (cell culture) Coffin et al 31 250-1000 µM 6 h Pre-treatment for 1 h, then co-exposure for 6 h Uribe et al 18 250-1500 μM 4 h Co-exposure for 4 h Kitcher et al 30 25-200 µM 24 h Co-exposure for 24 h Monroe et al 36 25 mg/kg Single microinjection CIS microinjection, 24 after drug microinjection Mackenzie and Raible 29 50 µM 24 h Co-exposure for 24 h Shin et al 37 50 µM 24 h Pre-treatment for 1 h, then CIS exposure for 24 h Thomas et al 27 50 µM 24 h Pre-treatment for 1 h, then CIS exposure for 24 h Zheng et al 38 50 µM 24 h Pre-treatment for 2 h, then co-exposure for 24 h Hirose et al 22 50 µM 6 h Co-exposure for 6 h Kruger et al 25 500 µM 6 h Co-exposure for 6 h Vargo et al 21 50-200 µM 16 h Co-exposure for 16 h Thomas et al 19 50-500 µM 6 and 24 h Pre-treatment for 1 h, then co-exposure for 6 h and 24 h Rocha-Sanchez et al 34 50-800 µM 6 h Pre-treatment for 2 h, then co-exposure for 6 h Gu et al 39 60 µM 24 h Pre-treatment for 4 h, then CIS exposure for 24 h Pang et al 28 600 µM 12 and 24 h Pre-treatment for 1 h, then co-exposure for 12 h and 24 h Wang et al 40 Data not available 24 h Co-exposure for 24 h and cathepsin were implicated to be involved in apoptotic processes. 44 The therapeutic impact of quinoxaline (Qx) against cisplatin was attributed to the prevention of apoptosis of the sensory hair cells in a still indeterminate way.…”