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, Department of Obstetrics and Gynecology, KGMU, Lucknow, 226003, Department of Zoology, BHU, Varanasi, Photobiology Division, CSIR-Indian Institute of Toxicology Research, Post Box No. 80, M.G. Marg, Lucknow, 226001, Department of Zoology, BHU, Varanasi, Department of Pathology, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Institute of Nanoscience & Technology Mohali-160062, Punjab, Department of Obstetrics and Gynecology, KGMU, Lucknow, 226003, Photobiology Division, CSIR-Indian Institute of Toxicology Research, Post Box No. 80, M.G. Marg, Lucknow, 226001
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.
