Antitumoral, antioxidant, and antimelanogenesis potencies of Hawthorn, a potential natural agent in the treatment of melanoma

Abstract

The lack of an efficient agent that does not have the disadvantage of low activity (kojic acid), high cytotoxicity, and mutagenicity (hydroquinone), poor skin penetration (arbutin), or low stability in formulation (glabridin) led us to continue our research on new antipigmentation/skin-lightening agents. Therefore, research of natural products that can modulate the metabolism of pigmentation is of great interest. Otherwise, malignant melanoma is one of the most aggressive forms of skin cancer, with high metastatic potential, and currently, there is no effective chemotherapy against invasive melanoma. Therefore, it is necessary to develop new drugs with potent activity and weak side effects against melanoma. The in-vitro anticancer effect of hawthorn was analyzed against B16F10 melanoma cells using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The effect of isolated compounds from hawthorn on melanogenesis in B16F10 melanoma cells was investigated by measuring the amounts of melanin and tyrosinase spectrophotometrically at 475 nm. Balb/c mice models inoculated with B16F10 mouse tumor cells were used to evaluate the in-vivo antitumoral potential of hawthorn by assessing its effect on the growth of transplanted tumors. The antioxidant potential of tested samples was evaluated in B16F10 and primary human keratinocyte cells using a cellular antioxidant activity assay. Hawthorn tested samples inhibited effectively the growth of melanoma cells in vitro. Furthermore, it appears that tested samples from hawthorn reduced melanogenesis by inhibiting the tyrosinase activity of B16F10 cells in a dose-dependent manner. In-vivo studies showed that hawthorn total oligomer flavonoids extract treatment at a dose of 150 mg/kg body weight for 21 days in implanted tumor mice resulted in significant inhibition of the tumor growth volume and weight. In addition, tested samples showed significant cellular antioxidant capacity against the reactive oxygen species in B16F10 and primary human keratinocyte cells. Our results indicate that hawthorn could be considered as a promising agent for the treatment of melanoma as it shows antitumor activity in vitro and in vivo. Moreover, hawthorn constituents are shown to be highly effective at inhibiting tyrosinase-mediated melanogenesis in vitro on melanoma cells by preventing oxidation in these cells and without affecting the viability of normal human keratinocyte cells. Then, hawthorn might also be used as a new candidate of natural skin depigmenting agents in skin care products.

Phytochemical composition and bioactivities of hawthorn (Crataegus spp.): review of recent research advances

“…Extract-induced growth inhibitory effect in human colorectal cancer cell lines HCT-116 and HT-29 was associated with DNA fragmentation, sub-G1 peak, loss of mitochondrial potential, and poly (ADP-ribose) polymerase (PARP) cleavage. The extract also induced the cleavage of caspase-8 and had no effect on steady-state levels of total Bcl-2 protein, whereas Bax levels decreased significantly in a dose-dependent manner in both tested cell lines (Mustapha et al, 2016b). It may also be mentioned that in searching of relatively mild and safe tyrosinase inhibitors, one of six isolated from C. pinnatifida seeds 8-0-4′ neolignans, demonstrated promising tyrosinase-inhibiting and good antioxidant activities (Huang et al, 2015b).…”

“…The studies performed by Mustapha et al (2015Mustapha et al ( , 2016a, c) demonstrated various effects of C. azarolus ethyl acetate extract as well as isolated from it hyperoside and vitexin-2″-O-rhamnoside. The extract and vitexin rhamnoside exhibited anti-proliferative activity against B16F10 melanoma cells and the ability to reduce melanin content by inhibiting the tyrosinase activities (Mustapha et al, 2015); it also demonstrated significant cellular antioxidant capacity against the ROS in B16F10 and primary human keratinocyte cells (Mustapha et al, 2016b). In addition, total oligomeric flavonoids extract (150 mg/kg body weight, 21 days) significantly inhibited tumor growth volume and weight in Balb/c mice inoculated with B16F10 cells and therefore was suggested as a new candidate for skin care products (Mustapha et al, 2016b).…”

“…The extract and vitexin rhamnoside exhibited anti-proliferative activity against B16F10 melanoma cells and the ability to reduce melanin content by inhibiting the tyrosinase activities (Mustapha et al, 2015); it also demonstrated significant cellular antioxidant capacity against the ROS in B16F10 and primary human keratinocyte cells (Mustapha et al, 2016b). In addition, total oligomeric flavonoids extract (150 mg/kg body weight, 21 days) significantly inhibited tumor growth volume and weight in Balb/c mice inoculated with B16F10 cells and therefore was suggested as a new candidate for skin care products (Mustapha et al, 2016b). The extract and hyperoside also exhibited an immunomodulatory effect by modulating macrophage lysosomal enzyme activity and NO release in mice and anti-inflammatory activity, which was concomitant with the cellular antioxidant effect against macrophages and solenocytes (Mustapha et al, 2016a).…”

Nitidine chloride acts as an apoptosis inducer in human oral cancer cells and a nude mouse xenograft model via inhibition of STAT3

“…Numerous natural products have been tested in efforts to discover novel anti-cancer therapeutic agents for the treatment of various tumors because natural agents typically exhibit fewer side effects than currently used anti-cancer chemotherapeutic drugs [ 14 , 15 ]. Nitidine chloride (NC), a natural benzophenanthridine alkaloid, is a major active compound present in a well-known traditional Chinese medicinal herb Zanthoxylum nitidum [ 16 ].…”

Arbutin increases Caenorhabditis elegans longevity and stress resistance

“…The latter group inhibits melanin synthase to lighten hair and it is the reason that arbutin was widely used in the cosmetic hairdressing industry. Furthermore, recent reports have showed that arbutin exhibited many biological activities, including antioxidant, diuretic, antibacterial, anti-inflammatory, anti-tussive, anticancer and so on ( Mustapha et al, 2016 ).…”