Two Metallic Nanoparticles Formulas of Phyllostachys heterocycla Extract Exhibited Potent Cytotoxicity against Ovarian Cancer Cells through Apoptosis Induction

Abstract

Phyllostachys heterocycla is well-known for its high diversity of bioactive metabolites, which are the reason for its various potential medical uses for which anticancer activity has been proven. Herein, Phyllostachys heterocycla extract was prepared in two different metallic nanoparticle formulas such as iron oxide nanoparticle-boron, and iron oxide nanoparticle-humic acid (Fe₂O₃ NP-B and Fe₂O₃ NP-HA) with average particle sizes of 12.25 nm and 15.80 nm, respectively. Phyllostachys heterocycla extract and the two nano-formulas were investigated to obtain their cytotoxic activity. The crude extract exhibited potent cytotoxic activity against the ovarian (OVCAR-3) cancer cell line, with IC₅₀ values of 16.3 µg/mL. In comparison, the two nano-loaded forms displayed a much more promising cytotoxic activity with IC₅₀ values of 0.9 µg/mL for Fe₂O₃ NP-HA, and 6.4 µg/mL for Fe₂O₃ NP-B. Additionally, NP-HA and NP-B showed potent cytotoxic activities against prostate (PC-3) and pancreatic (Panc1) cancer cell lines with IC₅₀ values of 2.31, 6.3 µg/mL for Fe₂O₃ NP-HA, and 14.9, 16.8 µg/mL for Fe₂O₃ NP-B. For apoptosis investigation, Fe₂O₃ NP-HA induced total ovarian apoptotic cell death by a 87.34-fold change, and necrosis by 1.29-fold change. Regarding cell cycle analysis, Fe₂O₃ NP-HA-PHE arrested the cell proliferation of OVCAR-3 cells in S-phase, with an increased cell population at S-phase of 42.6%. Additionally, it confirmed the apoptosis mechanism by inhibiting the antiapoptotic gene and activating the proapoptotic gene markers. Moreover, upon continuation of our phytochemical investigation of the plant, additional chemical components of the crude extract of Phyllostachys heterocycla were isolated using various chromatographic techniques. As a result, six compounds were isolated. By using different spectroscopic data, the chemical structures of the pure isolated compounds were assigned as stigmasterol (1), glyceryl monobehenate (2), vanillic acid (3), ferulic acid (4), catechin (5), and thymidine (6). These isolated compounds were previously reported for their potent cytotoxic activities against panel of cancer cell lines including pancreatic cancer and prostate cancer cell lines (Ferulic acid), beside the anti-tumor potential against ovarian cell lines (Stigmasterol). In addition to the cytotoxic activity against human larynx carcinoma HepG-2 cell lines (Catechin), human breast cancer MCF7 (Thymidine), and human colon cancer cell line HT-29 (Vanillic acid). Which may explain the significant cytotoxic and anticancer properities of the crude extract of Phyllostachys heterocycla.