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Anti-Cancer Agents in Medicinal Chemistry


ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Research Article

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

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*

Volume 17, Issue 12, 2017

Page: [1721 - 1732] Pages: 12

DOI: 10.2174/1871520617666170425094549

Price: $65


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.

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

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