Chemoprotective effect of the tetrahydrofuran lignan grandisin in the in-vivo rodent micronucleus assay

Abstract

Under the conditions tested herein, this study has shown that mice treated with grandisin presented, in a dose-dependent manner, a protective effect against cyclophosphamide-induced mutagenicity. This effect could be, at least in part, associated to grandisin bioactivation. These data open new perspectives for further investigation into the toxicology and applied pharmacology of grandisin.

Grandisin induces apoptosis in leukemic K562 cells

“…Finally, caspase activation (caspase-3, -6, -8 and -9) was detected after EAT cells were exposed to grandisin (Valadares et al, 2009). On-going studies performed by our group demonstrated that this lignan has a protective effect against cyclophosphamideinduced mutagenicity and this effect could be associated to grandisin bioactivation (Valadares et al, 2011).…”

“…Throughout history, natural compounds have been used for the treatment of cancer due to their safety, low toxicity, and availability from natural sources (Pratheeshkumar et al, 2012). Grandisin is a lignan extracted from Piper solmsianum which presents antitumoral properties as well as antimalarial and trypanocidal activities (Martins et al, 2003;Bernardes et al, 2006;Valadares et al, 2011). Despite its lymphocytic activities, grandisin did not exert mutagenic effects on the bone marrow cells of exposed mice.…”

“…Despite its lymphocytic activities, grandisin did not exert mutagenic effects on the bone marrow cells of exposed mice. Moreover, grandisin proved to be a potent antiangiogenic compound due to the prolonged survival of mice bearing breast carcinoma (Valadares et al, 2011). Other pharmacological properties, such as antinociceptive, anti-inflamatory and antioxidant activities, have also been attributed to grandisin, which thereby shows the therapeutic versatility of this compound (Carvalho et al, 2010).…”

In vitro metabolism of the lignan (−)‐grandisin, an anticancer drug candidate, by human liver microsomes

“…This compound has displayed several biological activities, such as trypanocidal activity against the trypomastigote form of Trypanossoma cruzi , larvicidal activity against the mosquito Aedes aegypti , and antinociceptive and anti‐inflammatory activities . More recently, many studies have evaluated its cytotoxic and antitumor activities, suggesting (−)‐grandisin as a potential anticancer agent …”

“…[14] More recently, many studies have evaluated its cytotoxic and antitumor activities, suggesting (À)grandisin as a potential anticancer agent. [13][14][15][16][17] To date, many investigations have been performed to explore (À)-grandisin metabolism using several in vitro models, such as fungi, [17,18] insects, [19] pig ceca, Jacobsen catalysts, [20] and rat hepatic microsomes. [21] Considering that the liver is the major drug-metabolizing organ, liver-derived systems are the most suitable for metabolic studies.…”