In vitro selective cytotoxicity of the dietary chalcone cardamonin (CD) on melanoma compared to healthy cells is mediated by apoptosis

Abstract

Malignant melanoma is an aggressive type of cancer and the deadliest form of skin cancer. Even though enormous efforts have been undertaken, in particular the treatment options against the metastasizing form are challenging and the prognosis is generally poor. A novel therapeutical approach is the application of secondary plant constituents occurring in food and food products. Herein, the effect of the dietary chalcone cardamonin, inter alia found in Alpinia species, was tested using human malignant melanoma cells. These data were compared to cardamonin treated normal melanocytes and dermal fibroblasts representing healthy cells. To investigate the impact of cardamonin on tumor and normal cells, it was added to monolayer cell cultures and cytotoxicity, proliferation, tumor invasion, and apoptosis were studied with appropriate cell biological and biochemical methods. Cardamonin treatment resulted in an apoptosis-mediated increase in cytotoxicity towards tumor cells, a decrease in their proliferation rate, and a lowered invasive capacity, whereas the viability of melanocytes and fibroblasts was hardly affected at such concentrations. A selective cytotoxic effect of cardamonin on melanoma cells compared to normal (healthy) cells was shown in vitro. This study along with others highlights that dietary chalcones may be a valuable tool in anticancer therapies which has to be proven in the future in vivo.

4-Hydroxychalcone Induces Cell Death via Oxidative Stress in MYCN-Amplified Human Neuroblastoma Cells

“…However, it is known that the number of hydroxyl groups and their positioning can regulate the ability of chalcones to uncouple the mitochondria by collapsing the mitochondrial membrane [38], suggesting that structural differences between chalcones may account for the differences in the magnitude of their cytotoxic effects on NB cells. Another chalcone, cardamonin, has been found to selectively induce death of human melanoma cells, and not on healthy human melanocytes or dermal fibroblasts [57]. This is consistent with the selectivity cytotoxicity of low doses of 4HC on MYCN -amplified NB but not on cultured midbrain neurons, found here in our study.…”

Phytochemical Composition, Antioxidant, Antiacetylcholinesterase, and Cytotoxic Activities of Rumex crispus L.

“…Likewise, the DCM extract was located close to MCF-7. This extract contains several compounds at medium polarity with a major compound: cardamon is known according to the literature by its cytotoxic properties [ 69 , 70 ].…”

Emerging roles of cardamonin, a multitargeted nutraceutical in the prevention and treatment of chronic diseases

“…(2019) In vivo H460 xenograft ↓Tumor growth, Ki-67, PI3K/Akt/mTOR Zhou et al. (2019) In vitro A549 ↓Cell migration, G2/M phase arrest, ↑apoptosis, ↑caspase-3/7, ↑caspase-9, ↑PARP cleavage, ↓Mcl-1, ↓p-mTOR, ↓p-4EBP1 C Break et al, (2018) Melanoma In vitro A375 ↓Cell viability, invasion, ↑apoptosis, caspase-3, ↑PARP Berning et al. (2019) Myeloma In vitro RPMI 8226, U266, ARH-77, RPMI 8226 ↓Cell proliferation ↑ Apoptosis, caspase-3, PARP, ↓Bcl-2, Bcl-xL, ↓ survivin, XIAP, cIAP-1, cIAP-2, NF-κB/p65, ↓IKK, IKKβ, p-IκBα, ICAM-1, COX-2, VEGF Qin et al (2012) NPC In vitro HK1 ↓Cell migration, G2/M phase arrest, ↑apoptosis, ↑caspase-3/7, ↑caspase-9, ↑PARP cleavage, ↓Mcl-1, ↓p-mTOR, ↓p-4EBP1 C Break et al., (2018) Ovarian Cancer In vitro SKOV3 ↓Cell viability, VEGF, HIF-1α, HIF-2α, ↓p-mTOR, p-S6K1 Xue et al, (2016) In vitro SKOV3 ↓p-Raptor, mTORC1, p-S6K1, Lamp2 Shi et al.…”

“…In addition, the treatment of CD was shown to induce apoptosis, suppress cell proliferation, invasion, etc. in human malignant carcinoma cell lines ( Berning et al., 2019 ). These studies indicated the possible use of CD as a therapeutic agent against melanoma ( Shannan et al., 2016 ).…”