Abstract
We previously discovered the antioxidant and antiprostate cancer effects of antler extract (AE), but whether it inhibits cisplatin- (Cis-) induced toxicity has not been investigated. In this study, the effect of AE on Cis-induced side effects in the kidney and liver using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide-based cytotoxicity and cell cycle assays in prostate cancer PC-3 cells in vitro is investigated. Furthermore, we used a xenograft mouse model of the same cells to examine the in vivo effects and mechanisms of action. Cis and Cis + AE treatment attenuated prostate cancer cell growth by inducing apoptosis in vitro. Cis + AE stimulated cleaved caspases 3, 7, and 9 and polyadenosine diphosphate ribose polymerase expression. Cis + AE treatment for 1 week significantly increased the superoxide dismutase and catalase antioxidant activity while thiobarbituric acid reactive substances decreased. The histopathological damage and tumor necrosis factor-α, interleukin- (IL-) 1β and IL-6, cyclooxygenase-2, and inducible nitric oxide synthase expression in the kidney and liver tissue decreased. Therefore, AE likely possesses antiprostate cancer activity and inhibits Cis toxicity.
Highlights
Prostate cancer (PC) is one of the most common malignancies and represents the second most common cause of cancer-associated mortalities among men in the US [1]
RNase A and Tween-20 were supplied by Novagen (Darmstadt, Germany). e PC-3 human prostate cancer cell line was obtained from the Korean Cell Line Bank (Seoul, Korea, KCLB number: 21435). e Roswell Park Memorial Institute (RPMI) 1640 medium, fetal bovine serum (FBS), penicillin/streptomycin (P/S), 0.5% trypsinethylenediaminetetraacetic acid (EDTA), and phosphatebuffered saline (PBS) for the cells culture were from Invitrogen (Carlsbad, CA, USA)
Effect of Cis and antler extract (AE) on Growth and Morphology of PC-3 Cells In Vitro. e effects of Cis and AE on the proliferation of PC-3 cells were investigated. e cell line was cultured in vitro with the same concentration of Ci (200 μM) and different concentrations of AE (125–1,000 μg/mL) for 24 h, and cell viability was measured using the MTT assay. e results demonstrated that the proliferation of PC-3 cells decreased more in the Cis and Cis + AE groups than it did in the control group
Summary
Prostate cancer (PC) is one of the most common malignancies and represents the second most common cause of cancer-associated mortalities among men in the US [1]. Hormonal therapy remains the most effective therapy for patients with advanced PC by inhibiting proliferation and inducing apoptosis of tumor cells (hormone-dependent) [2]. After short-term remissions (18–24 months), the growth of surviving tumor cells recurs with castrate-resistant prostate cancer (CRPC) with inevitable progression and death within 2 to 3 years in most men (hormone-independent) [3, 4]. Cisplatin (Cis) is a widely used anticancer drug and one of the most potent antitumor drugs used against a wide spectrum of malignancies including PC, testicular, bladder, head and neck, ovarian, breast, and lung cancer [5,6,7,8,9,10]. Despite its use as a chemotherapeutic agent, Cis exerts serious side effects in several organs including the kidneys and liver [13, 14] mainly due to its high accumulation in these organs [14, 15]. ere is evidence implicating oxidative stress in the pathogenesis of Cis-induced kidney and liver injury, mediated by Journal of Chemistry increased reactive oxygen species [16,17,18,19]. erefore, there is an urgent need to discover a novel, less toxic substance without potent antitumor activity
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