Apoptotic Cell Death Induction Through Pectin, Guar Gum and Zinc Oxide Nanocomposite in A549 Lung Adenocarcinomas
Indu Hira, Reena Kumari, Adesh K. Saini, Henok Gullilat, Vipin Saini, Anil Kumar, Reena V. Saini, M Mallath, D Taylor, R Badwe, G Rath, V Shanta, C Pramesh, R Digumarti, P Sebastian, B Borthakur, A Kalwar, S Kapoor, S Kumar, J Gill, Kuriakose, H Malhotra, S Sharma, S Shukla, L Viswanath, R Chacko, J Pautu, K Reddy, K Sharma, A Purushotham, R Sullivan, P Vaid, P Raizada, A Saini, R Saini, S Baig, I Seevasant, J Mohamad, A Mukheem, H Huri, T Kamarul, D Tang, R Kang, T Berghe, P Vandenabeele, G Kroemer, P Decker, S Muller, A Ayodele, A Valizadeh, M Adabi, S Esnaashari, F Madani, M Khosravani, M Adabi, N Zahin, R Anwar, D Tewari, M Kabir, A Sajid, B Mathew, M Uddin, L Aleya, M Abdel-Daim, G Sharma, M Naushad, B Thakur, A Kumar, P Negi, R Saini, A Chahal, A Kumar, F Stadler, U Aqil, Z Rad, J Mokhtari, M Abbasi, V Gollapudi, U R; Mallavarapu, J Seetha, V Duddela, V Amara, C Vatti, V S; Anumakonda, D Feldman, S Fu, Z Sun, P Huang, Y Li, N Hu, B Urbano, C Mella, M Vera, K Wong, A Lu, X Chen, Z Yang, E Zare, P Makvandi, A Borzacchiello
Abstract
Previously, we reported the immunostimulatory potential of the nanocomposite prepared from biopolymers (Pectin and Guar gum) and zinc oxide (Pec-gg-ZnO) on human peripheral-blood lymphocytes leading to enhanced anti-cancer immunity. The current study aims to describe the direct anti-cancer potential of Pec-gg-ZnO nanocomposite and the relevant mechanism of cell death induction in human lung carcinomas (A549). The cytotoxicity assay revealed the anti-cancer potential of Pec-gg-ZnO nanocomposite towards A549 cells, cervical adenocarcinoma (HeLa), and prostatic small cell carcinoma (PC-3). The IC50 values were 83.67 ± 0.10 μg/ml, 87.25 ± 0.03 μg/ml and 85.95 ± 0.03 μg/ml for A549, HeLa and PC-3 cells, respectively. The nanocomposite's cancer cells' killing capabilities were significantly higher than pectin and guar gum alone. Hemolysis assay revealed that synthesized Pec-gg-ZnO nanocomposite is biocompatible at 2.5 mg/ml. S phase arrest with enhanced sub-G1 (apoptotic cells) population was examined in A549 cells treated with Pec-gg-ZnO nanocomposite. The nanocomposite caused apoptosis of target cells by inducing mitochondrial depolarisation, reactive oxygen species generation, caspase-3 and Poly (ADP-ribose) polymerase 1 (PARP1) activation resulting in DNA fragmentation. Collectively, the current data revealed that Pec-gg-ZnO nanocomposite is a novel polymer-based anti-cancer agent capable of inducing apoptotic pathways in cancer cells.