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Today, herbs are used as adjuncts to reduce the toxicity of chemotherapy drugs. Here, Zataria-Multiflora Essential Oil (ZEO) was concomitantly employed with doxorubicin, as an anti-cancer drug, to reduce the doxorubicin dosage. The growth inhibition was determined using MTT assay in treated cells. The morphological alteration was observed by fluorescent staining. To verify and compare the apoptosis, AnnexinV-PI flowcytometry and DNA fragmentation assay were performed, and the influence of the compounds on ROS generation was assessed. Changes in MMP and protein expression were analyzed by flowcytometry and western blot, respectively. The results showed that ZEO can act as an amplifier to sensitize PC3 prostate cancer cells to undergo ROS generation and apoptosis. This amplification can heighten the doxorubicin efficacy in lower doses. Consequently, our results indicated that doxorubicin-ZEO combinatory treatment of PC3 cells can reduce the nonspecific toxicity of doxorubicin and can be considered as a candidate in combinatory therapy., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Efficacy of chemotherapy is limited by the resistance of cancer cells. Phytochemicals especially Essential Oils (EOs) provide an alternative mode of cancer therapy. However, EOs utilization is restricted because of low bioavailability, and high degradation. Nanoemulsification is a method developed to overcome these obstacles. Accordingly, Citrus-Pectin nanoemulsion of Zataria Essential Oil (CP/ZEONE) was prepared to evaluate the anticancer activity and the mechanisms responsible for the caused cytotoxicity. Physical properties and FTIR spectra of CP/ZEONE were characterized. CP/ZEONE progressively improves the suppression of viability of drug-resistant MCF-7, MDA-MB-231 breast cancer cells, and spheroids. It triggers apoptosis by increasing Reactive Oxygen Species (ROS), mitochondrial membrane potential (MMP) loss, DNA damage, G2 and S-phase arrest in MDA-MB-231 cells and spheroids respectively. Additionally, spectroscopy techniques revealed the interaction of CP/ZEONE with DNA via the formation of a groove binding/partial intercalative complex. Thus, ZEO-loaded CP Nano-particles can be further explored as a promising antiproliferative and therapeutic candidate against cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier B.V.)