Synergistic Effect of Graphene Oxide Coated Nanotised Apigenin with Paclitaxel (GO-NA/PTX): A ROS Dependent Mitochondrial Mediated Apoptosis in Ovarian Cancer

Title:Synergistic Effect of Graphene Oxide Coated Nanotised Apigenin with Paclitaxel (GO-NA/PTX): A ROS Dependent Mitochondrial Mediated Apoptosis in Ovarian Cancer

Volume: 17 Issue: 12

Author(s): Manish Kumar Pal, Shyam Pyari Jaiswar*, Ashish Dwivedi, Shruti Goyal, Vinay Nand Dwivedi, Anumesh Kumar Pathak, Vinod Kumar, Pushp Lata Sankhwar and Ratan Singh Ray*

Affiliation:

• Department of Obstetrics and Gynecology, KGMU, Lucknow, 226003,India

• Photobiology Division, CSIR-Indian Institute of Toxicology Research, Post Box No. 80, M.G. Marg, Lucknow, 226001,India

Keywords: Apigenin nanoparticle, apoptosis, caspase-3, SOD, Bax, Bcl-2.

Abstract: Background: Ovarian cancer is most lethal among all gynecologic malignancies. Paclitaxel (PTX) is well used chemotherapeutic regimen for cancer control; however its undesired toxicity has been a matter of concern for clinicians. Here, we used the graphene oxide coated nanotised apigenin (GO-NA) to enhance the efficacy of paclitaxel.

Objective: The combined use of paclitaxel (PTX) and nanotised apigenin (NA) may reduce the PTX dose and increase the efficacy.

Methods: GO and GO-Apigenin was prepared by modified Hummers method and the nanoparticles were characterized by dynamic light scattering and transmission electron microscopy. SKOV-3 cells were treated by DMSO, Group I (Control)-McCoy's 5A Medium, Group II-Paclitaxel (5nM), Group III- Nanotised Apigenin (GO-NA-10µM), Group IV- Paclitaxel (5nM) + GO-NA (10µM). Cell viability and IC-50 value were determined by MTT assay, synergism by Compusyn software, ROS by DCFH-DA assay, SOD activity by kit and MMP were examined by JC-1 and mitotracker/DAPI staining, cell cycle by flow cytometry, mRNA and protein level by Real Time-PCR and Western blot respectively

Results: Results showed that GO-NA-PTX enhanced the anti-proliferative effect in synergistic manner as compare to GO-NA and PTX alone. GO-NA-PTX significantly suppressed the SOD activity, promotes the ROS accumulation, mitochondrial depolarization, DNA integrity and cell cycle arrest collectively accord the apoptosis. Results of immunocytochemistry, RT-PCR and western blot showed up-regulation of caspase-3, Bax, and down-regulation of Bcl-2.

Conclusion: The combination of PTX with GO-NA produces synergistic effects in SKOV-3 cells via the modulation of pro and anti-apoptotic gene and may reduce side effects of PTX.

Cite this article as:

Pal Kumar Manish, Jaiswar Pyari Shyam*, Dwivedi Ashish, Goyal Shruti , Dwivedi Nand Vinay , Pathak Kumar Anumesh, Kumar Vinod, Sankhwar Lata Pushp and Ray Singh Ratan *, Synergistic Effect of Graphene Oxide Coated Nanotised Apigenin with Paclitaxel (GO-NA/PTX): A ROS Dependent Mitochondrial Mediated Apoptosis in Ovarian Cancer, Anti-Cancer Agents in Medicinal Chemistry 2017; 17 (12) . https://dx.doi.org/10.2174/1871520617666170425094549