TY - JOUR
T1 - Anti-cancer effect of Rumex obtusifolius in combination with arginase/nitric oxide synthase inhibitors via downregulation of oxidative stress, inflammation, and polyamine synthesis
AU - Ginovyan, Mikayel
AU - Javrushyan, Hayarpi
AU - Petrosyan, Gayane
AU - Kusznierewicz, Barbara
AU - Koss-Mikołajczyk, Izabela
AU - Koziara, Zuzanna
AU - Kuczyńska, Monika
AU - Jakubek, Patrycja
AU - Karapetyan, Anna
AU - Sahakyan, Naira
AU - Maloyan, Alina
AU - Bartoszek, Agnieszka
AU - Avtandilyan, Nikolay
N1 - Publisher Copyright:
© 2023 Elsevier Ltd
PY - 2023/5
Y1 - 2023/5
N2 - Cancer continues to be a leading cause of death worldwide, making the development of new treatment methods crucial in the fight against it. With cancer incidence rates increasing worldwide, ongoing research must focus on identifying new and effective ways to prevent and treat the disease. The combination of herbal extracts with chemotherapeutic agents has gained much interest as a novel strategy to combat cancer. Rumex obtusifolius L. is a wild plant known for its medicinal properties and is widely distributed worldwide. Our preclinical evaluations suggested that R. obtusifolius seed extracts possessed cancer-inhibiting properties and we also evaluated the beneficial effects of the arginase inhibitor NG-hydroxy-nor-L-arginine and nitric oxide inhibitor NG-nitro-L-arginine methyl ester in the treatment of breast cancer. The current study aimed to combine these observations and evaluate the antioxidant and antitumor properties of R. obtusifolius extracts alone and in combination with the arginase and nitric oxide synthase inhibitors. Metabolic characterization of the plant extract using a liquid chromatography/high-resolution mass spectrometry advanced system revealed the presence of 240 phenolic compounds many of which possess anticancer properties, according to the literature. In vitro studies revealed a significant cytotoxic effect of the R. obtusifolius extracts on the human colon (HT29) and breast cancer (MCF-7) cell lines. Thus, a new treatment approach of combining R. obtusifolius bioactive phytochemicals with the arginase and nitric oxide synthase inhibitors NG-nitro-L-arginine methyl ester and/or NG-hydroxy-nor-L-arginine, respectively, was proposed and could potentially be an effective way to treat breast cancer. Indeed, these combinations showed immunostimulatory, antiproliferative, antioxidant, anti-inflammatory, and antiangiogenic properties in a rat breast cancer model.
AB - Cancer continues to be a leading cause of death worldwide, making the development of new treatment methods crucial in the fight against it. With cancer incidence rates increasing worldwide, ongoing research must focus on identifying new and effective ways to prevent and treat the disease. The combination of herbal extracts with chemotherapeutic agents has gained much interest as a novel strategy to combat cancer. Rumex obtusifolius L. is a wild plant known for its medicinal properties and is widely distributed worldwide. Our preclinical evaluations suggested that R. obtusifolius seed extracts possessed cancer-inhibiting properties and we also evaluated the beneficial effects of the arginase inhibitor NG-hydroxy-nor-L-arginine and nitric oxide inhibitor NG-nitro-L-arginine methyl ester in the treatment of breast cancer. The current study aimed to combine these observations and evaluate the antioxidant and antitumor properties of R. obtusifolius extracts alone and in combination with the arginase and nitric oxide synthase inhibitors. Metabolic characterization of the plant extract using a liquid chromatography/high-resolution mass spectrometry advanced system revealed the presence of 240 phenolic compounds many of which possess anticancer properties, according to the literature. In vitro studies revealed a significant cytotoxic effect of the R. obtusifolius extracts on the human colon (HT29) and breast cancer (MCF-7) cell lines. Thus, a new treatment approach of combining R. obtusifolius bioactive phytochemicals with the arginase and nitric oxide synthase inhibitors NG-nitro-L-arginine methyl ester and/or NG-hydroxy-nor-L-arginine, respectively, was proposed and could potentially be an effective way to treat breast cancer. Indeed, these combinations showed immunostimulatory, antiproliferative, antioxidant, anti-inflammatory, and antiangiogenic properties in a rat breast cancer model.
KW - Antioxidant properties
KW - Breast cancer
KW - Cancer treatment
KW - Combination therapy
KW - L-arginine metabolic pathway
KW - Rumex obtusifolius
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U2 - 10.1016/j.biocel.2023.106396
DO - 10.1016/j.biocel.2023.106396
M3 - Article
C2 - 36918141
AN - SCOPUS:85150023797
SN - 1357-2725
VL - 158
JO - International Journal of Biochemistry and Cell Biology
JF - International Journal of Biochemistry and Cell Biology
M1 - 106396
ER -