Determination of Cytotoxic Activity of Sanguinaria canadensis Extracts against Human Melanoma Cells and Comparison of Their Cytotoxicity with Cytotoxicity of Some Anticancer Drugs

Abstract

Melanoma is an enormous global health burden, and should be effectively addressed with better therapeutic strategies. Therefore, new therapeutic agents are needed for the management of this disease. The aim of this study was the investigation of cytotoxic activity of some isoquinoline alkaloid standards and extracts obtained from Sanguinaria canadensis—collected before, during, and after flowering—against three different human melanoma cells (A375, G361, SK-MEL-3). The cytotoxicity of these extracts was not previously tested on these melanoma cell lines. Determination of alkaloid contents was performed by HPLC-DAD using Polar RP column and mobile phase containing acetonitrile, water, and 1-butyl-3-methylimidazolium tetrafluoroborate. The cytotoxicity of alkaloid standards was investigated by determination of cell viability and calculation of IC50 values. Significant differences were observed in the alkaloids content and cytotoxic activity of the extracts, depending on the season of collection of the plant material. In the Sanguinaria canadensis extracts high contents of sanguinarine (from 4.8543 to 9.5899 mg/g of dry plant material) and chelerythrine (from 42.7224 to 6.8722 mg/g of dry plant material) were found. For both of these alkaloids, very high cytotoxic activity against the tested cell lines were observed. The IC50 values were in the range of 0.11–0.54 µg/mL for sanguinarine and 0.14 to 0.46 µg/mL for chelerythrine. IC50 values obtained for Sanguinaria canadensis extracts against all tested cell lines were also very low (from 0.88 to 10.96 µg/mL). Cytotoxic activity of alkaloid standards and Sanguinaria canadensis extracts were compared with the cytotoxicity of anticancer drugs—etoposide, cisplatin, and hydroxyurea. In all cases except the one obtained for cisplatin against A375, which was similar to that obtained for Sanguinaria canadensis after flowering against the same cell line, IC50 values obtained for anticancer drugs were higher than the IC50 values obtained for sanguinarine, chelerythrine, and Sanguinaria canadensis extracts. Our results showed that Sanguinaria canadensis extracts and isoquinoline alkaloids, especially sanguinarine and chelerythrine, could be recommended for further in vivo experiments in order to confirm the possibility of their application in the treatment of human melanomas.

Rediscovery of Traditional Plant Medicine: An Underestimated Anticancer Drug of Chelerythrine

“…S. canadensis has a long history of curing cancer in clinical use since the mid-19th century, and people have used a black salve derived from S. canadensis (Jellinek and Maloney, 2005; Lin et al, 2018 ) to cure skin cancer ( Croaker et al, 2016 ). Basic research also confirmed the possibility of its application in the treatment of human cancer through the in vivo experiments involving the S. canadensis extracts ( Tuzimski et al, 2021 ). The anticancer activity of sanguinarine, the main component of S. canadensis , against various human malignancies has been validated and reviewed ( Achkar et al, 2017 ).…”

“…R.Br., and Sanguinaria canadensis L.) and Rutaceae (e.g., Zanthoxylum asiaticum (L.) Appelhans, Groppo & J.Wen) ( Zhang et al, 2005 ; Malikova et al, 2006 ; Wang et al, 2013 ). Direct scientific studies have proven that the abovementioned four plants have antitumor medicinal values ( Iwasaki et al, 2010 ; Deljanin et al, 2016 ; Ali et al, 2020 ; Tuzimski et al, 2021 ) , and CHE, as the most representative active compound for these plants, has also undergone a large number of studies on anticancer activity in vitro and in vivo , so there is a clear link between the compound and the traditional uses and the effects of these plants ( Chmura et al, 2000 ). ( Figure 2 )…”

“…The phosphorylation of histone H2AX was detected to evaluate the DNA damage related to behavioral activation therapy (BA) treatment, and CHE was further reported to increase the expression of gH2AX and regulate caspase-3 cleavage at different levels ( Hammerová et al, 2011 ). CHE showed strong cytotoxic activity against human melanoma cell lines (A375, G-361, and SK-MEL-3) with IC 50 values below 0.55 μg/ml compared with anticancer drugs (etoposide, cisplatin, and hydroxyurea), indicating that CHE has high anticancer potential in melanoma ( Tuzimski et al, 2021 ).…”

Phytochemical Profile and Anticancer Activity from Medicinal Plants Against Melanoma Skin Cancer: A Review

“…Standard cancer treatment includes surgery, chemotherapy, radiation therapy, and immunotherapy. However, to date, there is no effective strategy to treat melanoma in clinical practice due to the side effects of chemotherapy and the development of multidrug resistance Yang et al, 2018;Khalifa et al, 2019;Tuzimski et al, 2021). Therefore, it is necessary to find an efficient, effective drug with fewer side effects and toxicity to treat melanoma (Kim et al, 2018;Yang et al, 2018;Abdulridha et al, 2020).…”

“…Therefore, it is necessary to find an efficient, effective drug with fewer side effects and toxicity to treat melanoma (Kim et al, 2018;Yang et al, 2018;Abdulridha et al, 2020). Several studies have revealed that the phytochemical content of natural products has an anticancer activity that is very safe, non-toxic, readily available, and cost-effective (Khan et al, 2019;Mistiogiani et al, 2021;Tuzimski et al, 2021).…”