Anticancer activity of a novel methylated analogue of L-mimosine against an in vitro model of human malignant melanoma

• DOI: 10.1007/s10637-019-00809-0
• Publication Date: 2019-06-26T01:02:47Z
• Authors: Sotiris Kyriakou; Melina Mitsiogianni; Theodora Mantso; William Cheung; Stephen Todryk; Stephany Veuger; Aglaia Pappa; David Tetard; Mihalis I. Panayi...
• Keywords: Keratinocytes; Preclinical Studies; 0303 health sciences; B200; Antineoplastic Agents; Apoptosis; Cell Cycle Checkpoints; Cell Line; 3. Good health; 03 medical and health sciences; Cell Line, Tumor; Carcinoma, Squamous Cell; Humans; Mimosine; Reactive Oxygen Species; Melanoma

SummaryThe anticancer activity of a series of novel synthesized, hydroxypyridone-based metal chelators (analogues of L-mimosine) was evaluated in an in vitro model of melanoma consisting of malignant melanoma (A375), non-melanoma epidermoid carcinoma (A431) and immortalized non-malignant keratinocyte (HaCaT) cells. More specifically, we have demonstrated that the L-enantiomer of a methylated analogue of L-mimosine (compound 22) can exert a potent anticancer effect in A375 cells when compared to either A431 or HaCaT cells. Moreover, we have demonstrated that this analogue has the ability to i) promote increased generation of reactive oxygen species (ROS), ii) activate both intrinsic and extrinsic apoptosis and iii) induce perturbations in cell cycle growth arrest. Our data highlights the potential of compound 22 to act as a promising therapeutic agent against an in vitro model of human malignant melanoma.