Antitumor Effect of Manool in a Murine Melanoma Model

Abstract

The manool diterpene, found in abundance in Salvia of ficinalis L., showed a selective cytotoxic effect against murine melanoma cells. Therefore, the present study aimed to evaluate the antitumor potential of manool in a murine melanoma model, administered by three routes: oral, subcutaneous, and intraperitoneal. In addition, the antimelanoma effect of manool (orally) combined with cisplatin (subcutaneous) was evaluated. The results obtained revealed that manool, administered by the three routes, was able to significantly decrease the mass and frequency of mitosis of the tumor tissue. The data obtained revealed that manool, at a dose of 20 mg/kg, was able to significantly decrease the tumor mass when administered by the three routes, with the percentages of reduction being equivalent to 62.4% (oral), 48.5% (intraperitoneal), and 38.8% (subcutaneous), without toxic effects. The treatment of manool plus cisplatin led to 86.7% reduction in tumor mass, higher than that observed in treatment with manool or cisplatin alone (50.7%), although signs of toxicity have been observed. The results also showed that treatments with manool (20 mg/kg orally) and/or cisplatin did not alter the activity of caspase 3 cleaved in tumor tissue. Therefore, manool revealed a promising antimelanoma effect, but without involvement of the caspase 3 cleaved pathway.

Metabolites Profile of Extracts and Fractions of Erythroxylum mexicanum Kunth by UHPLC‐QTOF‐MS/MS and its Antibacterial, Cytotoxic and Nitric Oxide Inhibitory Activities

“…In addition, manool was significantly more cytotoxic for tumor cell lines than V79 normal cell line (IC 50 =49.3 μg/mL) [28] . In another study, manool (also isolated from S. officinalis L.) showed a selective cytotoxic effect against murine melanoma cells, and using an in vivo model in mice, a significantly decrease of the tumor mass was observed by reduction percentages of 62.4 % (oral), 48.5 % (intraperitoneal) and 38.8 % (subcutaneous) at dose of 20 mg/kg, without toxic effects [29] …”

“…[28] In another study, manool (also isolated from S. officinalis L.) showed a selective cytotoxic effect against murine melanoma cells, and using an in vivo model in mice, a significantly decrease of the tumor mass was observed by reduction percentages of 62.4 % (oral), 48.5 % (intraperitoneal) and 38.8 % (subcutaneous) at dose of 20 mg/kg, without toxic effects. [29] The studies described above indicate that the manool diterpenoid might be involved partly to the selective cytotoxicity induced by the HSF and CSF fractions towards cancer cells. Furthermore, as we previously mentioned, this same compound may be involved in the antibacterial activity of the same fractions.…”

Volatile Compounds in Norway Spruce (Picea abies) Significantly Vary with Season

“…Most compounds present in higher percentages were previously studied for their potential biological or therapeutic activities, which suggests possible usages of P. abies essential oil in conventional and complementary medicine, such as aromatherapy. Manool possesses antigenotoxic, anticarcinogenic, and anti-inflammatory potential [ 19 ], while an anti-melanoma effect was shown in vivo in mice [ 20 ]. Bornyl acetate possesses anti-inflammatory [ 21 ] properties; limonene possesses antihyperalgesic [ 22 , 23 ], antidiabetic [ 24 ], anti-inflammatory [ 25 ], and antioxidative [ 25 ] potential; α-cadinol has antifungal [ 26 ] properties; β-pinene antimicrobial [ 27 ] has antioxidative properties [ 28 ] and, in combination with linalool, antidepressant properties [ 29 ]; borneol has antiglycemical [ 30 ], antihyperlipidemic [ 30 ], antioxidative [ 30 ], and antinociceptive [ 31 ] properties; camphene has antitumor [ 32 ], antioxidative [ 33 ], and hypolipidemic [ 34 ] properties; abienol has antifungal, antimicrobial, and antineoplastic properties [ 35 ]; α-pinene has antimicrobial [ 27 , 36 ], antioxidative [ 28 ], anti-inflammatory [ 37 ], gastroprotective [ 38 ], and antinociceptive properties [ 39 ]; myrcene has antioxidative [ 40 ] and anti-inflammatory properties [ 41 ]; (E)-caryophyllene has anti-inflammatory [ 42 ], anticonvulsant [ 43 ], and antinociceptive properties [ 44 ]; T-muurolol has antifungal properties [ 26 ]; δ-cadinene has anticancer [ 45 ] and acaricidal properties [ 46 ]; α-humulene has anti-inflammatory properties [ 47 ]; and camphor has anti-inflammatory [ 48 ], eucalyptol antibacterial […”