Abstract
Breast cancer is the most frequently diagnosed cancer worldwide, and the incidence rate has increased enormously over the last three decades. Rab proteins are members of the Rab GTPase superfamily. The aberrant function of these proteins leads to the development of tumors. Mentha longifolia var. asiatica and Zygophyllum arabicum have been known for their therapeutic potential for ages. The present study aimed to synthesize ZnO nanoparticles encapsulated with the extracts of M. longifolia var. asiatica and Z. arabicum and evaluating their therapeutic potential against breast cancer, targeting the Rab22A gene and its protein. UV-Vis spectrophotometer showed characteristic absorbance peaks at 295 nm and 345 nm for Z. arabicum and M. longifolia var. asiatica ZnONPs, respectively. The FTIR bands of Z. arabicum nanoparticles suggested the presence of aldehydes, alcohols, and polyols whereas bands of M. longifolia var. asiatica ZnONPs suggested the presence of carboxyl groups, hydroxyl groups, alkynes, and amines. SEM revealed the size of Z. arabicum ZnO NPs to be 25 ± 4 nm with a spherical shape as compared to nanoparticles of M. longifolia var. asiatica having a size of 35 ± 6 nm with a hexagonal shape. EDX determined the elemental composition of both particles. The cytotoxicity of both plant extracts and respective NPs was determined against the MCF-7 breast cancer cell line, which was found to be significant with an IC50 value of 51.68 μM for Z. arabicum and 88.02 μM for M. longifolia var. asiatica ZnO compared to plant extracts (64.01 μM and 107.9 μM for Z. arabicum and M. longifolia var. asiatica). The gene expression and protein levels of Rab22A were decreased in nanoparticle-treated cells as compared to the control group. The apoptotic role of synthesized nanoparticles against the MCF-7 cell line was also determined by the expression of apoptotic pathway genes and proteins (bax, caspase 3, caspase 8 and caspase 9). All samples showed significant apoptotic activity by activating intrinsic and extrinsic pathway genes. The activity of Z. arabicum was more eminent as compared to M. longifolia var. asiatica which was evident by the greater expression of studied genes and proteins as determined by Real-time qPCR and ELISA. This is the first-ever report describing the comparative analysis of the efficacy of Z. arabicum and M. longifolia var. asiatica ZnONPs against breast cancer.
Publisher
Public Library of Science (PLoS)
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