Plant-derived bioactive molecules (PBAM) that provide health benefits, including antioxidant and anti-cancer benefits, are collectively known as phytochemicals. Combinatorial phytochemotherapy is defined as an experimental method using a combination of certain PBAMs that have demonstrated antineoplastic activity, together with conventional chemotherapeutic agents. In this study, the antiproliferative activity of the phytochemical lutein was examined alone or in combination with each of the phytochemicals capsaicin, curcumin, or the conventional chemotherapeutic drug, camptothecin. The effects of these combinations on the proliferation of the prostate adenocarcinoma cell line, LnCap, were examined. Lutein exhibited significant antiproliferative activity. When combined with low-dose camptothecin, lutein significantly enhanced antiproliferative activity. Capsaicin and curcumin when employed with lutein, showed significant antiproliferative effects that were greater than that of lutein alone. Levels of c-Jun N-terminal kinases (JNK) are an indicator of chemotherapy-induced apoptosis. Capsaicin activated the JNK pathway and potentiated the antiproliferative activity of lutein. Lutein and curcumin appear to function in a manner that does not require or interfere with JNK activation. The importance of these observations rests with the potentiating effects of lutein on the traditional chemotherapy agent camptothecin, which promises a novel phytochemotherapeutic approach for treating and preventing cancer. These studies also suggest that lutein potentiates the effects of other phytochemicals such as capsaicin and curcumin. Furthermore, our studies indicate that each phytochemical may function through unique signaling pathways. Further study is warranted to examine their mechanisms.
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