Jatropha-6(17),11E-diene class derivatives induce apoptosis effects in OVCAR-3 and Caov-4 ovarian cancer cell lines via a mitochondrial pathway

Abstract

We investigated the molecular mechanism of apoptosis induced by novel jatropha-6(17),11E-diene class derivatives, compounds A, B, and C that were extracted from Euphorbia osyridea Boiss, in the ovarian cancer cell lines Caov-4 and OVCAR-3. The OVCAR-3 and Caov-4 cell lines were treated with different concentrations of these compounds. Cytotoxicity was evaluated using MTT, clonogenic survival assay, and flow cytometry assays. The production of reactive oxygen species (ROS), mitochondrial membrane potential (Δ), and the activity of caspase 3 and 9 were evaluated. Compounds A, B, and C reduced cell viability in a dose-dependent manner (P < 0.05). The IC values were calculated as 46.27 ± 3.86, and 38.81 ± 3.30 μmol/L for compound A, 36.48 ± 3.18 and 42.59 ± 4.50 μmol/L for compound B, and 85.86 ± 6.75 and 75.65 ± 2.56 μmol/L for compound C against the Caov-4 and OVCAR-3 cell lines, respectively. Apoptosis evaluation showed that jatrophane derivatives increase both early and late apoptosis (P < 0.01). These compounds also increased ROS generation, Δ, and the activity of caspase 3 and 9 in the treated cells. These results showed that compounds A and B have significant inhibitory effects on OVCAR-3 and Caov-4 proliferation and induction of apoptosis.

A2a adenosine receptor agonist improves endoplasmic reticulum stress in MIN6 cell line through protein kinase A/ protein kinase B/ Cyclic adenosine monophosphate response element‐binding protein/ and Growth Arrest And DNA‐Damage‐Inducible 34/ eukaryotic Initiation Factor 2α pathways

“…Finally, colonies were fixed with paraformaldehyde 4% for 20 min at room temperature and stained with crystal violet (0.5% in PBS) (Sigma‐Aldrich Merck (St. Louis, MI)). Plating efficiency and surviving fraction (SF) were calculated for each treatment as previously described (Bahmani, Keyvanloo Shahrestanaki, Ghanadian, Hajiahmadi, & Aghaei, ). The results were presented as SF values.…”

“…Louis, MI)). Plating efficiency and surviving fraction (SF) were calculated for each treatment as previously described (Bahmani, Keyvanloo Shahrestanaki, Ghanadian, Hajiahmadi, & Aghaei, 2017).…”

Adenosine protects pancreatic beta cells against apoptosis induced by endoplasmic reticulum stress

“…Colonies were counted under a magnified field using an inverted microscope. Colony numbers was estimated and then plating efficiency (PE) and surviving fraction (SF) calculated as mentioned previously …”

Jatrophane and rearranged jatrophane-type diterpenes: biogenesis, structure, isolation, biological activity and SARs (1984–2019)

“…It showed weak cytotoxicity with IC 50 values of 55.67 ± 7.09 lM against MDA-MB and moderate cytotoxicity with IC 50 values of 24.33 ± 3.21 lM against MCF-7 cell line (Shadi et al 2015). Bahmani et al (2017) evaluated cytotoxicity and the molecular mechanism of apoptosis induced by the novel 'jatropha-6(17),11E-diene' class derivatives (342-344) previously extracted from E. osyridea on Caov-4 and OVCAR-3 ovarian cancer cell lines. 133 showed the lowest activity against Caov-4 and OVCAR-3 ovarian cell lines (IC 50 = 85.86 ± 6.75 and 75.65 ± 2.56 lM, respectively).…”

“…Induced ROS production in Caov-4 and OVCAR-3 was evaluated 2.6 and 4.4 for 131; and 4.7 and 9.9 fold/control for 343, respectively. In this regard, ROS overproduction and trigger of caspase activation might be the potential mechanism of these compounds interposing apoptosis in the ovarian cancer cells by mitochondria or pro-oxidant activity of ionizable groups of 342 and 343 (Bahmani et al 2017).…”