Anti-cancer potential of selected Nigerian medicinal plants: Gliricidia sepium (Jacq.) Walp. and Maerua angolensis DC

Abstract

Two commonly used plants were selected for anti-cancer activity and safety evaluation. To achieve this, an ethnobotanical study was undertaken and use-value analysis was employed to select the plants. The ethanolic and petroleum ether of each plant's crude extracts were subjected to phytochemical analysis, toxicity studies and anticancer testing. Both qualitative and quantitative phytochemical analyses were undertaken using standard methods. Acute and subacute oral toxicity studies were done using the OECD limit test and 28-day repeated dose methods, respectively. Brine shrimp lethality assay was used to screen for plant toxicity. The MTT assay was performed on prostate (DU 145), breast (HCC 1395) and colorectal (CT 26) cancer cell lines. Vero E6 and doxorubicin were used as a normal cell line and a positive drug control, respectively. Apoptotic potential of the extracts on DU145 and HCC1395 cell lines was evaluated by qRT-PCR for the expression of p53 and Bax genes. Data was subjected to One-Way ANOVA followed by Bonferroni multiple comparison test using SPSS, version 21.0. The values were expressed as means ± standard deviation (SD). The P-value <0.05 was considered statistically significant. Maerua angolensis and Gliricidia sepium were the most commonly used plants. Both G. sepium and M. angolensis extracts were rich in phytochemical compounds, with plants harvested during the rainy season being the richer. Both extracts were safe with LD50>5000 mg/kg. Compared to Cyclophosphamide (LD50= 59.70), both PE extracts were highly cytotoxic (LD50 =7.91-47.10). The subacute toxicity study showed a significant decline in K (4.60±0.3) and WBC (7.23±0.6) for G. sepium, and Cl, WBC and lymphocytes for M. angolensis (p > 0.05) compared to the control. The stomach and spleen showed mild erosive gastritis and moderate splenic hyperemia, respectively. The ethanolic extract of G. sepium showed high antiproliferative potential (IC50 <20µg/mL) and high selectivity index (7.2-12.3) in all cell lines. Maerua angolensis ethanolic extract also exhibited high antiproliferative activity but with a very low selectivity index (0.3-0.8) compared to doxorubicin (1.8-4.0). The qRT-PCR analysis of HCC1395 and DU145 cancer cell lines demonstrated upregulation of p53 with a high fold change (61.3-22.6) and slightly upregulated Bax genes with a low fold (1.05-1.17). In conclusion, G. sepium ethanolic extract exhibited antiproliferative activity and promoted apoptosis by inducing p53/Bax-mediated signalling pathway safely with high selectivity level. Maerua angolensis extracts, though, possessed anticancer activity, exhibited low selectivity index and some organ toxicity. Therefore, communities should use it with caution, and both extracts may be researched further to isolate and elucidate the bioactive compounds responsible for their anticancer activities.