Green extraction of essential oils from Pistacia lentiscus resins: Encapsulation into Niosomes showed improved preferential cytotoxic and apoptotic effects against breast and ovarian cancer cells

Abstract

The essential oils extracted from Pistacia lentiscus resins possess promising antiproliferative effects against ovarian and breast cancer cells because of their high content of bioactive compounds. However, PO has many drawbacks that hinder its application in breast cancer therapy, such as increased volatility, hydrophobicity, and limited bioavailability. In this study, niosomal formulation loaded with Pistacia lentiscus essential oil (PO) was formulated with improved stability and cytotoxicity against two cancer cell lines. In this regard, PO was extracted from the resins of Chios mastic utilizing a green approach, hydrodistillation. Its chemical composition was analyzed using gas-chromatography–mass spectrometry. PO loaded-niosomes (PO/Ns) were prepared using the thin-film hydration method. The prepared nanovesicles were spherical and had an average size of 230.3 ± 3.7 nm, polydispersity index of 0.13 ± 0.03, and ζ potential (ZP) of −20.36 ± 4.89 mV. PO/Ns had high entrapment efficiency (EE) of 80.59 ± 3.37% and displayed a sustained release manner of PO (83.74 ± 3.34%) over 72 h. Moreover, the developed PO/Ns formulation exhibited outstanding stability in terms of size, PDI, ZP, and EE% when stored for 21 days. SRB assay showed that the IC50 values of PO against ovarian (Skov-3) and breast (MCF-7) cancer cell lines improved from 57.04 to 69.1 μg/mL to 4.88 and 7.38 μg/mL, respectively, when encapsulated in niosomes (PO/Ns). Loading PO in niosomes (PO/Ns) increased its cytotoxicity by 10-folds against Skov-3 and MCF-7 cancer cells. On the other hand, the safety of both PO and PO/Ns was evident by a computed IC50 of >200 μg/mL against the normal breast epithelial cell line (MCF10A). PO/Ns showed enhanced apoptotic effects (combined early and late apoptosis) of 9-fold and 4-fold against Skov-3 and MCF-7 cells, respectively, as compared to unloaded PO treatment. Cell cycle analysis revealed that PO/Ns mainly targets the sub-G1 phase, where it traps the cells, providing further evidence for the induction of apoptosis in both SKOV-3 and MCF-7 cancer cells. Real-time PCR (RT-qPCR) was performed to quantify the gene expression of pro-apoptotic markers as Bak and Bax, as well as the antiapoptotic marker Bcl-2 upon exposure to PO and PO/Ns treatments. Both PO and PO/Ns demonstrated a remarkable ability to upregulate Bak and Bax, and downregulate Bcl-2. As expected, the upregulation of pro-apoptotic genes and induction of mitochondrial death was significantly higher with PO/Ns than pure PO treatment among the two investigated cell lines (Skov-3 and MCF-7). Essential oils extracted from Pistacia lentiscus resins and encapsulated into niosomes showed significant cytotoxic and apoptotic effects against breast and ovarian cancer cells.