Functionalized Sulfur-Containing Heterocyclic Analogs Induce Sub-G1 Arrest and Apoptotic Cell Death of Laryngeal Carcinoma In Vitro
B. Haridevamuthu,
Tamilvelan Manjunathan,
Carlton Ranjith Wilson Alphonse,
Rajendran Saravana Kumar,
Sundaram Thanigaivel,
Somasundaram Chandra Kishore,
Vickram Sundaram,
Pushparathinam Gopinath,
Jesu Arockiaraj,
Stefano Bellucci
Affiliations
B. Haridevamuthu
Department of Biotechnology, College of Science and Humanities, SRM Institute of Science and Technology, Kattankulathur, Chennai 603203, Tamil Nadu, India
Tamilvelan Manjunathan
Department of Chemistry, College of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur, Chennai 603203, Tamil Nadu, India
Carlton Ranjith Wilson Alphonse
Molecular and Nanomedicine Research Unit, Centre for Nanoscience and Nanotechnology, Sathyabama Institute of Science and Technology, Chennai 600119, Tamil Nadu, India
Rajendran Saravana Kumar
Chemistry Division, School of Advanced Sciences, VIT University, Chennai Campus, Chennai 600127, Tamil Nadu, India
Sundaram Thanigaivel
Department of Biotechnology, College of Science and Humanities, SRM Institute of Science and Technology, Kattankulathur, Chennai 603203, Tamil Nadu, India
Somasundaram Chandra Kishore
Department of Biomedical Engineering, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences, Chennai 602105, Tamil Nadu, India
Vickram Sundaram
Department of Biotechnology, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences, Chennai 602105, Tamil Nadu, India
Pushparathinam Gopinath
Department of Chemistry, College of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur, Chennai 603203, Tamil Nadu, India
Jesu Arockiaraj
Department of Biotechnology, College of Science and Humanities, SRM Institute of Science and Technology, Kattankulathur, Chennai 603203, Tamil Nadu, India
Stefano Bellucci
INFN—Laboratori Nazionali di Frascati, 00044 Frascati, Italy
In this study, we speculate that the hydroxyl-containing benzo[b]thiophene analogs, 1-(3-hydroxybenzo[b]thiophen-2-yl) ethanone (BP) and 1-(3-hydroxybenzo[b]thiophen-2-yl) propan-1-one hydrate (EP), might possess antiproliferative activity against cancer cells. Hydroxyl-containing BP and EP show selectivity towards laryngeal cancer cells (HEp2), with IC50 values of 27.02 ± 1.23 and 35.26 ± 2.15 µM, respectively. The hydroxyl group present in the third position is responsible for the anticancer activity and is completely abrogated when the hydroxyl group is masked. BP and EP enhance the antioxidant enzyme activity and reduce the ROS production, which are correlated with the antiproliferative effect in HEp-2 cells. An increase in the BAX/BCL-2 ratio occurs during the BP and EP treatment and activates the caspase cascade, resulting in apoptosis stimulation. It also arrests the cells in the Sub-G1 phase, indicating the induction of apoptosis. The molecular docking and simulation studies predicted a strong interaction between BP and the CYP1A2 protein, which could aid in combinational therapy by enhancing the bioavailability of the drugs. BP and EP possess an antioxidant property with low antiproliferative effects (~5.18 µg/mL and ~7.8 µg/mL) as a standalone drug, therefore, they can be combined with other drugs for effective chemotherapy that might trigger the effect of pro-oxidant drug on healthy cells.
