Methotrexate and 5-aminoimidazole-4-carboxamide riboside exert synergistic anticancer action against human breast cancer and hepatocellular carcinoma

Abstract

Aim: To investigate the influences of methotrexate (MTX) on the anticancer actions and pharmacokinetics of 5-aminoimidazole-4-carboxamide riboside (AICA riboside) in human breast cancer and hepatocellular carcinoma. Methods: Human breast cancer cell line MCF-7 and human hepatocellular carcinoma cell line HepG2 were examined. The cell proliferation was assessed using a sulforhodamine B assay. Western blotting and radioactivity assays were used to analyze the phosphorylation of AMPK. The DNA synthesis was analyzed with BrdU incorporation. Nude mice bearing MCF-7 cell xenografts were used to for in vivo study. MTX (50 mg/kg, ip, per week) and AICA riboside (200 mg/kg, ip, every other day) were administered the animals for 2 weeks. The concentrations of AICA riboside and its active metabolite AICA ribotide in the plasma and tumors were measured with HPLC.

Overview of Dual-Acting Drug Methotrexate in Different Neurological Diseases, Autoimmune Pathologies and Cancers

“…MTX is used (alone or in combination) to treat both early-stage (as well after surgery and other treatments) and advanced-stage breast cancer. Some selected application of MTX in breast cancer therapy are presented below [196,[213][214][215][216][217][218][219][220][221]244,[265][266][267], Table 2. Martin et al described numerous combination regimens applied in metastatic breast cancer, such as CTX, MTX, 5-FU (CMF), 5-FU, Adriamycin, CTX (FAC) and MTX in combination with tegafur and uracil followed by LV rescue (MUL) [213,214].…”

“…Under these conditions, MM chemotherapy proved to be effective and tolerated, however, only in patients who kept good performance status and bone marrow function even after multiple chemotherapy regimens. The combined effects of MTX and 5-aminoimidazole-4-carboxamide riboside (AICAR) on tumour cell proliferation were the object of research conducted by Cheng et al [220]. In the frame of these researches, the influence of MTX on AICAR anticancer action and pharmacokinetics in human breast cancer as well as concentration of active AICAR metabolites in plasma and tumours were studied.…”

Dexamethasone suppresses the growth of human non-small cell lung cancer via inducing estrogen sulfotransferase and inactivating estrogen

“…Cells were then cultured in RPMI-1640 medium mixed with 1 nmol/L E2, and various concentrations of DEX or TAM were added. The corresponding survival rates of the cells were calculated [15,28] . Sulforhodamine B assay on the sulfation-inhibitory effects of triclosan The SRB assay was further performed to investigate the effects of triclosan, an inhibitor of sulfation [29] , on the survival rate of A549 and H1299 cells exposed to DEX.…”

CKS protein overexpression renders tumors susceptible to a chemotherapeutic strategy that protects normal tissues

“…The cells were injected into the fourth, right, inguinal mammary fat pad. Mice were randomly divided into four groups and biweekly intraperitoneal injection of 0.9% saline, methotrexate (50 mg/kg) [ 36 ], gemcitabine (80 mg/kg) [ 37 ], or the combination of methotrexate and gemcitabine began once tumor volume reached ∼50 mm 3 . Tumor volume was measured biweekly using digital calipers (Traceable) and calculated as (width 2 × length)/2 = mm 3 [ 21 , 38 ].…”