Identification and biotin receptor-mediated activity of a novel seleno-biotin compound that inhibits viability of and induces apoptosis in ovarian cancer cells. (25th September 2022)

• Record Type: Journal Article
• Authors: Raza, Asif; Singh, Amandeep; Amin, Shantu; Spallholz, Julian E.; Sharma, Arun K.
• Is Part Of: Chemico-biological interactions. Volume 365(2022)
• Publication Date: 2022-09-25
• Subjects: Ovarian cancer -- Selenium -- Structure-activity relationship -- Oxidative stress -- Biotin -- Seleno-biotin -- Receptors -- Reactive oxygen species; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2022.110071
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: A series of seleno-biotin analogs were synthesized and their anticancer activity and mode of action were assessed using ovarian cancer cells. Compound 2, out of the other analogs, in direct comparison to biotin alone, more effectively reduced the cell viability and induced apoptosis in ovarian cancer cell lines in a dose dependent manner as demonstrated by the cell viability assay, trypan blue dye exclusion assay, Annexin V/7-AAD, and Caspase 3/7 apoptosis assays. Furthermore, compound 2 showed efficacy better than 5-fluorouracil (5-FU) and similar to cisplatin, in vitro ; notably it was more cytotoxic to drug-resistant Hey A8 cells than cisplatin. The cytotoxicity of compound 2 was primarily mediated by reactive oxygen species (ROS) as demonstrated by DCFDA based ROS estimation. Biotin receptors (BR) saturation and the use of a BR negative cell line showed a significant decline in the cytotoxic ativity of the compound 2, confirming that its activity is BR-mediated. These experiments demonstrated that selenium modified biotin which contains an ester linked redox cycling selenocyanate group has the potential for human therapeutic applications against ovarian and other cancers over-expressing BR. Graphical abstract: Image 1 Highlights: Novel seleno-biotin analogs were synthesized and their cytotoxicity was evaluated in ovarian cancer cell lines. Ester-linked ethyl selenocyanato biotin 2 showed potent cytotoxicity against all the ovarian cancer cell lines. Compound 2 induced apoptosis, inhibited S-phase transition to G2/M, and induced ROS in OVCAR-3 cells. The biotin receptor saturation assay confirmed biotin receptor-mediated cytotoxicity of Compound 2.