Cytotoxic and Apoptotic Activity of the Novel Harmine Derivative ZC-14 in Sf9 Cells

Abstract

Harmine, one of the natural β-carboline alkaloids extracted from Peganum harmala L., exhibits broad spectrum but limited insecticidal ability against many pests. So there is an urgent need to synthesize novel derivatives with high efficiency. In the present study, a new synthetic compound, [1-(2-naphthyl)-3-(2-thioxo-1,3,4-oxadiazol-5-yl) β-carboline] (ZC-14), showed a strong proliferation inhibition effect against the Spodoptera frugiperda Sf9 cell line in a dose-dependent manner. Simultaneously, apoptosis induced by 7.5 μg/mL ZC-14 was confirmed with physiological and biochemical evidence, including typical apoptosis characteristics with shrinkage, apoptotic bodies, nuclear condensation/fragmentation, a clear DNA ladder, and a series of apoptotic rates. In addition, mitochondria were confirmed to be involved in apoptosis induced by ZC-14 accompanied with the loss of mitochondrial membrane potential (Δψm), the release of cytochrome c from mitochondria into the cytosol and increased expression of cleaved-caspase-3. However, harmine could not induce apoptosis at the same concentration. In summary, these data indicated that compound ZC-14 has a higher cytotoxicity than harmine against Sf9 cells. Besides, it exhibited an anti-proliferative effect in Sf9 cells via inducing apoptosis in which the mitochondrial apoptotic pathway plays a crucial role.

Cytotoxic effects of β‐asarone on Sf9 insect cells

“…Our finding that β‐asarone induces apoptosis in Sf9 cells will help to elucidate the mechanism underlying its insecticidal activity. Recently, the ability of apoptosis induction in insect cells by many active compounds, including azadirachtin (Rembold & Annadurai, ), abamectin (Huang, Tian et al, ), harmine derivative ZC‐14 (Zhang, Zhang, Shu, Cui, & Zhong, ), spinosad (Yang et al, ), and camptothecin (Huang, Lv, Hu, & Zhong, ), suggesting that toxicity that induces apoptosis is conserved in many botanical insecticides. Azadirachtin is categorized as an antimitotic insecticide that targets cell division and cause proliferation inhibition and apoptosis in insect cell lines (Huang, Shui et al, ; Huang et al, ; Rembold & Annadurai, ; Salehzadeh et al, ).…”

Evolution from Natural β-Carboline Alkaloids to Obtain 1,2,4,9-tetrahydro-3-thia-9-aza-fluorene Derivatives as Potent Fungicidal Agents against Rhizoctonia solani

“…The hyphae were treated with a stain-fixative at 4 °C overnight, and then stained with 1 mL Hoechst 33258 solution (Beyotime) at 25 °C for 10 min after being washed twice with 0.1 M PBS. The samples were observed under a fluorescence microscopy [23].…”

Synthesis and In Vitro Antitumor Activity of Novel Bivalent β-Carboline-3-carboxylic Acid Derivatives with DNA as a Potential Target

“…β -carboline alkaloids are a class of natural and synthetic indole alkaloids with a wide range of pharmacological activities, including antitumor, antiviral, antiparasitic, and antibacterial activities [ 5 , 6 ]. Particularly, previous studies have shown that β -carboline alkaloids exerted antitumor activity through insertion into DNA [ 10 , 11 , 12 ], inducing apoptosis [ 13 , 45 ], inhibiting CDKs [ 16 ], and topoisomerase I and II activity [ 13 , 15 ]. The substitution at the C 3 and N 9 positions of β -carbolines could significantly increase their DNA insertion ability [ 7 ].…”