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Chemical composition and pharmacological bio-efficacy of Parrotiopsis jacquemontiana (Decne) Rehder for anticancer activity.

ABSTRACT: Consistent STAT3 (Single transducer and activator of transcription 3) activation is observed in many tumors and promotes malignant cell transformation. In the present investigation, we evaluated the anticancer effects of Parrotiopsis jacquemontiana methanol fraction (PJM) on STAT3 inhibition in HCCLM3 and MDA-MB 231 cells. PJM suppressed the activation of upstream kinases i.e. JAK-1/2 (Janus kinase-1/2), and c-Src (Proto-oncogene tyrosine-protein kinase c-Src), and upregulated the expression levels of PIAS-1/3 (Protein Inhibitor of Activated STATs-1/3), SHP-1/2 (Src-homology region 2 domain-containing phosphatase-1/2), and PTP-1β (Protein tyrosine phosphatase 1 β) which negatively regulate STAT3 signaling pathway. PJM also decreased the levels of protein products conferring to various oncogenes, which in turn repressed the proliferation, migration, invasion, and induced apoptosis in cancer cell lines. The growth inhibitory effects of PJM on cell-cycle and metastasis were correlated with decreased expression levels of CyclinD1, CyclinE, MMP-2 (Matrix metalloproteinases-2), and MMP-9 (Matrix metalloproteinases-9). Induction of apoptosis was indicated by the cleavage and subsequent activation of Caspases (Cysteine-dependent Aspartate-directed Proteases) i.e. caspase-3, 7, 8, 9, and PARP (Poly (ADP-ribose) polymerase) as well as through the down-regulation of anti-apoptotic proteins. These apoptotic effects of PJM were preceded by inhibition of STAT3 cell-signaling pathway. STAT3 was needed for PJM-induced apoptosis, and inhibition of STAT3 via pharmacological inhibitor (Stattic; SC-203282) abolished the apoptotic effects. Conclusively, our results demonstrate the capability of PJM to inhibit cancer cell-proliferation and induce apoptosis by suppressing STAT3 via upregulation of STAT3 inhibitors and pro-apoptotic proteins whereas the down-regulation of upstream kinases and anti-apoptotic protein expression. In future, one-step advance studies of PHM regarding its role in metastatic inhibition, immune response modulation for reducing tumor, and inducing apoptosis in suitable animal models would be an interesting and promising research area.

SUBMITTER: Ali S

PROVIDER: S-EPMC8381063 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundConventional cancer treatments, such as chemotherapy, radiation therapy, and surgery, often affect the patients' quality of life due to their serious side effects, indicating the urgent need to develop less toxic and more effective alternative treatments. Medicinal plants and their derivatives are invaluable sources for such remedies. The present study aimed to determine the chemical composition, anticancer and antibacterial activities of Nepeta mahanesis essential oil (EO).MethodsThe chemical composition of EO was analyzed by gas chromatography-mass spectrometry (GC-MS). Cytotoxicity and apoptosis/necrosis induction of EO was analyzed by MTT assay and Flow cytometry. Real-time PCR was performed to evaluate the Bax/Bcl2 gene expression. Also, the effect of the EO on the cells' mitochondrial membrane potential (MMP) and ROS level was assessed. DPPH assay was done to assess the free radical scavenging activity of the EO. The Antimicrobial activity, MIC, and MBC of the oil were determined via well-diffusion and broth microdilution methods.ResultsBased on the GC-MS analysis, 24 compounds were identified in the EO, of which 1,8-cineole (28.5%), Nepetalactone (18.8%), germacrene D (8.1%), and β-pinene (7.2%), were the major compounds. Also, the EO showed considerable cytotoxicity against MCF-7, Caco-2, SH-SY5Y, and HepG2 after 24 and 48 h treatment with IC50 values between 0.0.47 to 0.81 mg/mL. It was revealed that this compound increased the Bax/Bcl2 ratio in the MCF-7 cells and induced apoptosis (27%) and necrosis (18%) in the cells. Moreover, the EO treatment led to a substantial decrease in MMP, which is indicative of apoptosis induction. A significant increase in ROS level was also detected in the cells following exposure to the EO. This compound showed strong DPPH radical scavenging activity (IC50: 30). It was also effective against Gram-positive E. faecalis (ATCC 29,212) and Gram-negative E. coli (ATCC 11,333) bacteria.ConclusionsThe results of this study demonstrated that the EO of N. mahanesis could be considered a bioactive product with biomedical applications that can be used as an alternative cancer treatment and applied in the biomedical industries.

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Chemical composition and pharmacological bio-efficacy of Parrotiopsis jacquemontiana (Decne) Rehder for anticancer activity.

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