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

Publisher： Bentham Science Publishers

E-ISSN： 1875-5992|17|12|1721-1732

ISSN： 1871-5206

Source： Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Cancer Agents), Vol.17, Iss.12, 2018-01, pp. : 1721-1732

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Abstract

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

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

Methods: GO and GO-Apigenin was prepared by modified Hummers method and the nanoparticles werecharacterized by dynamic light scattering and transmission electron microscopy. SKOV-3 cells were treated byDMSO, Group I (Control)-McCoy#39;s 5A Medium, Group II-Paclitaxel (5nM), Group III- Nanotised Apigenin(GO-NA-10#181;M), Group IV- Paclitaxel (5nM) + GO-NA (10#181;M). Cell viability and IC-50 value were determinedby MTT assay, synergism by Compusyn software, ROS by DCFH-DA assay, SOD activity by kit andMMP were examined by JC-1 and mitotracker/DAPI staining, cell cycle by flow cytometry, mRNA and proteinlevel by Real Time-PCR and Western blot respectively

Results: Results showed that GO-NA-PTX enhanced the anti-proliferative effect in synergistic manner ascompare to GO-NA and PTX alone. GO-NA-PTX significantly suppressed the SOD activity, promotes theROS accumulation, mitochondrial depolarization, DNA integrity and cell cycle arrest collectively accord theapoptosis. 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 themodulation of pro and anti-apoptotic gene and may reduce side effects of PTX.