Assessment of Photo-Induced Cytotoxic Activity of Cachrys sicula and Cachrys libanotis Enriched-Coumarin Extracts against Human Melanoma Cells

Abstract

Photochemotherapy is one of the most interesting current therapeutic approaches for the treatment of melanoma. Different classes of naturally occurring phytochemicals demonstrated interesting photoactive properties. The aim of this study was to evaluate the photocytotoxic potential of two Cachrys species from Southern Italy: C. sicula and C. libanotis (Apiaceae). The enriched-coumarin extracts were obtained from aerial parts through both traditional maceration and pressurized cyclic solid-liquid (PCSL) extraction using Naviglio extractor®. Qualitative and quantitative analyses of furanocoumarins were performed with GC-MS. The photocytotoxic effects were verified on C32 melanoma cells irradiated at a dose of 1.08 J/cm2. The apoptotic responses were also assessed. Moreover, phenolic content and the in vitro antioxidant potential were estimated. Xanthotoxin, bergapten, and isopimpinellin were identified. All the samples induced concentration-dependent photocytotoxic effects (IC50 ranging from 3.16 to 18.18 μg/mL). The C. libanotis sample obtained with Naviglio extractor® was the most effective one (IC50 = 3.16 ± 0.21 μg/mL), followed by C. sicula sample obtained with the same technique (IC50 = 8.83 ± 0.20 μg/mL). Both Cachrys samples obtained through PCSL induced up-regulation of apoptotic signals such as BAX (Bcl2-associated X protein) and PARP (poly ADP-ribose polymerase) cleavage. Moreover, these samples proved to be more photoactive, giving a greater upregulation of p21 protein in the presence of UVA radiation. Obtained results suggest that investigated species could be promising candidates for further investigations aimed to find new potential drugs for the photochemotherapy of skin cancer.

Towards an In Vitro 3D Model for Photosynthetic Cancer Treatment: A Study of Microalgae and Tumor Cell Interactions

“…Among all melanoma cells available for research, the C32 human cell line was chosen due to being amelanotic, thus not interfering with the illumination settings of the study. Moreover, they have been previously combined with photosensitizers [ 41 , 42 ] and used for toxicological screenings of plant compounds [ 43 , 44 , 45 , 46 ]. Finally, due the feasibility of further illumination and administration of microalgae in prospective patients, melanomas represent a good candidate for the translation of this concept into clinics.…”

Cachrys spp. from Southern Italy: Phytochemical Characterization and JAK/STAT Signaling Pathway Inhibition

“…(n = 3). 3 Marrelli et al, 2021 [11]. Results are expressed as mg of chlorogenic acid (for phenolics) and mg of quercetin (for flavonoids) per g of dry plant material.…”

“…The name C. ferulacea is a synonymous of Prangos ferulacea Lindl., being the Cachrys group divided into a number of genera including not only Cachrys and Prangos , but also Alocacarpum , Azilia , Bilacunaria , Diplotaenia , Eriocycla and Ferulago [ 10 ]. The major secondary metabolites of these species were identified in coumarins and furanocoumarins, among which bergapten represents one of the most interesting molecules [ 11 ].…”

“…In a previous study, we already reported the interesting coumarin content of C. libanotis extract [ 11 ]. Here, the phytochemical characterization and quantitative analyses were performed by means of gas chromatography—mass spectrometry (GC-MS) on the other two Cachrys species, and Principal Component Analysis (PCA) was used to highlight the differences among the composition of the three extracts.…”

Xanthotoxin (8‐methoxypsoralen): A review of its chemistry, pharmacology, pharmacokinetics, and toxicity

“…Therefore, screening for natural anti‐cancer drugs has become an essential tool in the treatment and prevention of cancer (Lu et al, 2021). More and more studies have shown that XAT has great potential in treating cancer, and according to incomplete statistics, XAT can inhibit a range of diseases such as colon cancer (Bartnik, Slawinska‐Brych, Zurek, Kandefer‐Szerszen, & Zdzisinska, 2017), Hepatocellular carcinoma (HCC) (El‐Nakkady, Roaiah, El‐Serwy, Bassyouni, & Soliman, 2015; Palacharla et al, 2019), skin cancer (Marrelli et al, 2021), T‐cell lymphoma (Cunderlikova et al, 2014), prostate cancer, and glioma (Lu et al, 2017). The anti‐cancer mechanism of XAT mainly includes two aspects, one is the induction of apoptosis and the other is the inhibition of disorderly cell proliferation.…”