Anticancer Effects of Wild Mountain Mentha longifolia Extract in Adrenocortical Tumor Cell Models

Abstract

Mint [Mentha longifolia (L.) Hudson] is an aromatic plant that belongs to Lamiaceae family. It is traditionally used as herbal tea in Europe, Australia and North Africa and shows numerous pharmacological effects, such as spasmolytic, antioxidant, antimicrobial and anti-hemolytic. Recently, its antiproliferative role has been suggested in a small number of tumor cell models, but no data are available on adrenocortical carcinoma, a malignancy with a survival rate at 5 years of 20%-30% which frequently metastasize. This work aimed to study the effects of Mentha longifolia L. crude extract (ME) on two adrenocortical tumor cell models (H295R and SW13 cells). Chemical composition of ME was assessed by gaschromatography/mass spectrometry and NMR spectroscopy analysis. Brine shrimp lethality assay showed ME effects at >0.5 µg/µl (p < 0.05). Cell viability and vitality were determined by MTT, SRB, and trypan blue assays in H295R and SW13 cells. The antiproliferative effects of ME were more evident in SW13 cells at 72 h (ME > 0.5 µg/µl, p < 0.05). Combination of ME with mitotane (approved drug for adrenocortical carcinoma) seemed not to reinforce the efficacy of the herb. As control, human fibroblasts were treated with ME with no effect on cell viability. Clonogenic assay was concordant with previous cell viability tests (ME > 0.5 µg/µl, p < 0.05), while Wright staining demonstrated the presence of both necrotic and apoptotic cells. Cell cycle analysis showed a strong increase in subG0/G1 phase, related to cell death. Furthermore, MAPK and PI3k/Akt pathways were modulated by Western blot analysis when treating cells with ME alone or combined with mitotane. The crude methanolic extract of wild mountain mint can decrease cell viability, vitality and survival of adrenocortical tumor cell models, in particular of SW13 cells. These data show the potential anticancer effects of ME, still more work is needed to corroborate these findings.FIGURE 7 | Representative Western blot analysis for SW13 and H295R cells. Lines 1 and 5: untreated control. Lines 2 and 6: 0.5 mg/ml ME. Lines 3 and 7: mitotane 10 mM. Lines 4 and 8: ME 0.5 mg/ml + mitotane 10 mM. Experiments performed in triplicate.Patti et al.

Plant Natural Compounds in the Treatment of Adrenocortical Tumors

“…MAPK and PI3K/Akt pathways were involved in the antiproliferative effect of oregano. Similarly, a second work explored a collected wild mountain Mentha longifolia (L.) Hudson extract in the same cell lines [104]. e research showed that the extract exerted antiproliferative effect by MTT assay only in SW13 cells at 0.5 μg/μL, together with an increase in subG0/ G1 phase.…”

“…Quercetin effectively increased aromatase activity (CYP19), a key enzyme involved in the synthesis of estrogens from androgens, differently from All reduced deoxycorticosterone and androstenedione levels by the inhibition of 3β-HSD [89] Whole plant extracts SW13 and H295R cells IC50 of 0.4 μg/μL and 0.8 μg/μL, respectively Methanolic extract of Origanum vulgare impacted on colony formation, cell cycle, and morphological changes, with a prevalence of necrotic process over apoptosis, MAPK, and PI3K/Akt pathways involvement [103] SW13 and H295R cells 0.5 μg/μL in SW13 Methanolic extract of Mentha longifolia increased subG0/G1 phase, induced cytotoxicity, in both cell lines. In SW13 cells, the mixture modulated the MAPK pathway [104] International Journal of Endocrinology apigenin and resveratrol and other flavonoids that are recognized as aromatase inhibitors [144].…”

The Wonderful Activities of the Genus Mentha: Not Only Antioxidant Properties

“…Differently, aqueous extract of M. spicata showed cytotoxicity effect on U937 leukemia cells (IC 50 = 4.8 mg/mL) [ 151 ]. The methanolic extract of M. longifolia at a concentration >0.5 µg/µl demonstrated antiproliferative effects in adrenocortical tumor cell lines, with modulating activity on MAPK and PI3k/Akt pathways [ 152 ]. Ohara and Matsuhisa screened 120 medicinal plants for antitumor effects against the okadaic aid (OA) tumor inducer and noted that Mentha species were among the most effective in antiproliferative activity (86–100%) [ 153 ].…”

Molecular Interaction Studies and Phytochemical Characterization of Mentha pulegium L. Constituents with Multiple Biological Utilities as Antioxidant, Antimicrobial, Anticancer and Anti-Hemolytic Agents

“…Numerous biological activities have previously been reported for M. pulegium extract as well as its essential oils, and occasionally the activity has differed based on cultivation conditions. Previous studies reported a number of biological activities including antimicrobial activity against many microorganisms [ 8 , 9 ], decremental inflammation with oral mucosa treatment, anti-hemolytic, and anticancer activities [ 10 ] of Mentha.…”