ABSTRACT: The cytotoxic effects and related mechanisms of pumpkin (Cucurbita pepo) seed ethanolic (PS-ET) and aqueous (PS-AQ) extracts were evaluated in LNCaP prostate cancer cells. LNCaP cells were exposed to extracts for 24hr. The viability of LNCaP cells was significantly decreased following 24 hr treatment with both PS-AQ ([IC.sub.50]= 49 [micro]g/ml) and PS-ET ([IC.sub.50] = 55 [micro]g/ml) extracts. The reactive oxygen species levels were also significantly increased (4.1 [+ or -] 0.2 and 3 [+ or -] 0.3 fold) and mitochondrial membrane potential was reduced with both PS-AQ and PS-ET extracts respectively. Both extracts induced DNA fragmentation and PolyADP-ribosepolymerase (PARP) cleavage. Additionally PS-ET produced a 5 ([+ or -] 0.2) and 3.5 ([+ or -] 0.4) fold increase in caspase 3 and 9 activities respectively, whilePS-AQproduceda 7 ([+ or -] 0.4) and 3 ([+ or -] 0.9) fold increase in caspase 3 and 9 activities respectively. Our results confirm that the cytotoxic activity of both PS extracts is mediated through oxidative stress and mitochondrial depolarization. Further, the cleavage of PARP, caspase activation and DNA fragmentation confirms the induction of apoptosis as the major cytotoxic modality for the extracts. These findings could hold positive implications for potential pumpkin seed extract intervention in prostate cancer therapy.
KEY WORDS: Cytotoxicity, Pumpkin Seed Extracts, Prostate Cancer Cells
Prostate cancer is one of the most common cancers in the Jamaican population and the leading cause of cancer related deaths in the Caribbean, despite improvement in screening methods and accessibility to healthcare (Jemal et al., 2011; Gibson et al., 2010). Globally, it is the second most frequently diagnosed cancer and in the United States it is the second leading cause of cancer death in men (Jemal et al., 2011). There are several approaches to prostate cancer treatment depending on the stage of the disease. Chemotherapy is applicable in cases where the cancer has spread outside the prostate gland and when hormone therapy fails. First line chemotherapeutic agents are taxanes such as docetaxel and cabazitaxel. Docetaxel is commonly met with high levels of resistance and adverse events including bleeding, anemia, neuropathy and depressed cardiac function (Hwang, 2012); hence there is significant interest in exploring new chemotherapeutic agents for prostate cancer that might present with safer treatment profiles. One potential source of such anti-cancer agent could be the Pumpkin plant.
Cucurbita pepo Linn that is commonly referred to as Pumpkin, is a plant belonging to the family Cucurbitaceae (Oloyede, 2012). The plant along with its fruits and seeds are a main staple in the diet of many countries including Africa, Europe and Jamaica (Oloyede, 2012; Chevallier, 1996). There is strong evidence of a protective role of Pumpkin seed oil on prostate health, where is has been shown to inhibit the development of testosterone induced prostatic hyperplasia in rats (Gossell-Williams et al., 2006; Tsai et al., 2006) as well as to improve quality of life and prostate specific antigen (PSA) levels in men with benign prostatic hyperplasia (BPH) (Hong et al., 2009). The extracts of pumpkin seeds have...
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