Monitoring and risk assessment of pesticide residues in selected herbal medicinal products in Ghana.

The high patronage of herbal medicinal products in Ghana for the treatment of diverse disease conditions raises concerns about patient safety, given that much of the raw materials for production are obtained from the wild or farmlands potentially exposed to varied agrochemical residues. Therefore, the work sought to investigate the contamination of herbal medicinal products with pesticide residues and assess the potential risk posed to patients. As a result, validated gas chromatography with mass spectrometry as a detector was used to determine forty-two pesticides in thirty herbal medicinal products. The performance parameters of the method such as linearity, accuracy, and precision were found as acceptable. Pesticide residues such as chlorpyrifos and/or bifenthrin were found in 4/30 herbal medicinal products. Specifically, 3/30 herbal medicinal products contained only one pesticide, while 1/30 was contaminated with both pesticide residues. The levels of pesticide residue contamination ranged between 2.5 and 5.0 µg/kg. The acute hazard quotient and chronic hazard quotient for the two pesticide residues were evaluated and ranged between 0.21 and 0.92% and between 8.21 × 10-4 and 5.88 × 10-3%. The detected pesticide residue levels are below the maximum residue limit values, which may not cause acute and chronic health risks due to intake of the selected herbal medicinal product. Nevertheless, patient safety and potential public health risk can be reduced by regular monitoring, and regulation of pesticide residue levels in herbal medicinal products.

CXCR4-Targeted Necrosis-Inducing Peptidomimetic for Treating Breast Cancer.

Triple-negative breast cancer is an aggressive subtype with a high recurrence rate, potential for metastasis, and a poor prognosis. The chemokine receptor, CXCR4, is a promising molecular target in breast cancer therapy. Here, we have developed a CXCR4-targeted antitumor peptidomimetic (named CTCE-KLAK), which is a fusion of the CXCR4 receptor antagonist CTCE-9908 and the D-form of proapoptotic peptide (KLAKLAK)2, for the treatment of breast cancer. First, we investigated the in vitro antitumor activity of CTCE-KLAK against various breast cancer cells and noncancerous mammary epithelial cells. CTCE-KLAK showed cell-selective cytotoxicity and induced rapid necrotic cell death in breast cancer cells but not in normal cells. In contrast, unconjugated peptides such as the carboxylate analogues of CTCE-9908 and D(KLAKLAK)2 were not cytotoxic to these cells. The tumor selectivity of CTCE-KLAK for cytotoxic activity depends on its internalization into tumor cells. There was no cleavage of caspase-3, caspase-7, or PARP1 in CTCE-KLAK-treated cells. In addition, cell death by CTCE-KLAK was not prevented by z-VAD-fmk, a pan-caspase inhibitor that inhibits cisplatin-induced cell death. These data indicate that the CTCE-KLAK conjugate is a cell-selective inducer of necrosis. Furthermore, we evaluated the in vivo antitumor activity of CTCE-KLAK in the 4T1 mouse metastatic breast cancer model. Intravenous administration of CTCE-KLAK significantly inhibited tumor growth and lung metastasis. Together, these findings suggest that the necrosis-inducing peptidomimetic CTCE-KLAK is a promising CXCR4-targeted agent for treating triple-negative breast cancer.