S, at the same time as cytotoxic effects on B16-F10-Nex2 and
S, also as cytotoxic effects on B16-F10-Nex2 and A2058 cells, apoptosis, ROS production and enhanced autophagy [104]. Another instance came from the synthetic antitumour compound 1,4-naphthoquinone derivative CB533, which induced AKT-dependent autophagy in A375 cells and mimicked ROS-induced stress signalling with out causing ROS production and apoptosis [105]. Recently, a semisynthetic p-quinol, protoapigenone 1 -O-butyl ether (PABut), was tested as an antimelanoma agent in parallel with its all-natural congener protoapigenone (PA), a derivative of apigenin [106]. Both compounds showed cytotoxicity toward A375 cells and tumour selectivity. Certainly, PABut and PA elevated apoptosis at the early and the late stage, respectively. Furthermore, PABut was much more effective than PA in enhancing autophagy even though PABut and PA similarly stimulated ROS production, which also promoted senescence. On B16 cells, octahedral platinum(IV) complexes (satraplatin analogues) exerted anticancer activity by means of a non-apoptotic cell death associated with cell membrane SB 271046 supplier damage. Of note, octahedral platinum(IV) complexes induced oxidative strain and necrosis-like cell death, but not autophagy [107]. In addition, no effects on autophagy were observed in vivo and in vitro B16 models employing the organic compound O,O-diethyl-(S,S)-ethylenediamineN,N di-2-(3-cyclohexyl) propanoate dihydrochloride, which triggered apoptosis, disruption of mitochondrial membrane potential and oxidative pressure, leading to decreased tumour development [108]. Benefits on the toxicity of copper complexes mononuclear complex 1 and dinuclear complex 2 have shown that susceptibility to these compounds in SK-Mel 05 and SK-Mel 147 cells is related to melanin content and is favoured by UV-B irradiation, which induces melanogenesis, ROS formation, and apoptosis, probably involving autophagic death process [109]. Conversely, apoptosis induction and autophagic flux blockade was detected soon after the administration of photoactive NADPH analogue NS1 [110]. In distinct, NS1 triggered cancer cell death by inhibition of NADPH oxidases NOX in A375, SK-Mel 28 and in key melanoma cells from sufferers. Additionally, NS1 established an early ER pressure induced by calcium-dependent redox-sensitive ion channels. These events initiated apoptosis and autophagy, Pinacidil custom synthesis despite the fact that the autophagic course of action was incomplete. 3.three. All-natural Substances The value of antioxidant polyphenols from nature in opening up new avenues in skin cancer therapies has been highlighted recently [111]. Within this line, quite a few organic molecules, alone or in mixture with a well-known pharmacological agent, have simultaneously activated apoptosis and autophagy and induced ROS accumulation in A375 cells. Shikonin, a botanical substance extracted from Lithospermum erythrorhizon, exerted antiproliferative action, led to apoptosis and triggered autophagy, upregulating p38 levels. Of interest, autophagy machinery activated by shikonin exerted a protective function against apoptosis and ROS-mediated ER anxiety and p38 pathways had been involved in each apoptosis and autophagy regulations [112]. In the same cell line, sasanquasaponin III (SQS III), a member of SQS class of triterpenoid saponins isolated from theaceous plant, acted as an inhibitory molecule on viability and induced apoptosis and autophagy, both associated with ROS accumulation [113]. The powerful anticancer activity of SQS III suggested that ROS are essential at the crossroad among autophagy and apoptosis. Indeed, SQS II.