Abstract
Jatropha meal produced from the kernel of Jatropha curcas Linn. grown in Malaysia contains phorbol esters (PEs). The potential benefits of PEs present in the meal as anticancer agent are still not well understood. Hence, this study was conducted to evaluate the cytotoxic effects and mode of actions of PEs isolated from Jatropha meal against breast (MCF-7) and cervical (HeLa) cancer cell lines. Isolated PEs inhibited cells proliferation in a dose-dependent manner of both MCF-7 and HeLa cell lines with the IC50 of 128.6 ± 2.51 and 133.0 ± 1.96 µg PMA equivalents/mL respectively, while the values for the phorbol 12-myristate 13-acetate (PMA) as positive control were 114.7 ± 1.73 and 119.6 ± 3.73 µg/mL, respectively. Microscopic examination showed significant morphological changes that resemble apoptosis in both cell lines when treated with PEs and PMA at IC50 concentration after 24 h. Flow cytometry analysis and DNA fragmentation results confirmed the apoptosis induction of PEs and PMA in both cell lines. The PEs isolated from Jatropha meal activated the PKC-δ and down-regulated the proto-oncogenes (c-Myc, c-Fos and c-Jun). These changes probably led to the activation of Caspase-3 protein and apoptosis cell death occurred in MCF-7 and HeLa cell lines upon 24 h treatment with PEs and PMA. Phorbol esters of Jatropha meal were found to be promising as an alternative to replace the chemotherapeutic drugs for cancer therapy.
Highlights
Jatropha curcas Linn. is receiving a lot of attention nowadays due to the demand for seed oils for the biodiesel industry [1]
The high performance liquid chromatography (HPLC) analysis (Figure 2) illustrated that the Jatropha meal phorbol esters (PEs) appeared in four peaks which were labelled as PE1, PE2, PE3 and PE4
The PEs isolated from Jatropha meal activated the protein kinase C (PKC)-δ and down-regulated the proto-oncogenes (c-Myc, c-Fos and c-Jun)
Summary
Jatropha curcas Linn. (family Euphorbiaceae) is receiving a lot of attention nowadays due to the demand for seed oils for the biodiesel industry [1]. The byproduct which is called Jatropha meal contains bioactive peptides [7] and phytochemicals including phenolics, phytic acid, trypsin inhibitors, lectins, saponins and phorbol esters (PEs) [8]. The presence of phorbol esters was first reported in croton oil [9]. They are polycyclic compounds, where two hydroxyl groups on neighboring carbon atoms are esterified with fatty acids. Concomitant to the PEs present in other plant materials, PEs from Jatropha meal may have cytotoxic properties and could be an alternative source of chemotherapeutic drugs. This research was conducted to evaluate the cytotoxic effects and mode of actions of PEs isolated from Jatropha meal against breast (MCF-7) and cervical (HeLa) cancer cell lines
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