Abstract
The present study was aimed to assess cellular and molecular events involved in the chemopreventive activities of β-cryptoxanthin derived from mandarin oranges (Citrus unshiu Marc.) on human cervical carcinoma (HeLa) cells. In vitro experiments established that β-cryptoxanthin significantly inhibited the proliferation of HeLa cells with the IC50 value of 4.5 and 3.7 µM after 24 and 48 h of treatments, respectively. β-cryptoxanthin-treated HeLa cells exhibited enhanced levels of oxidative stress correlated with significant downregulation of anti-apoptotic Bcl-2, and upregulation of pro-apoptotic Bax mRNA expression. Moreover, β-cryptoxanthin triggered nuclear condensation and disruption of the integrity of the mitochondrial membrane, upregulated caspase-3, -7, and -9 mRNA, and enhanced activation of caspase-3 proteins, resulting in nuclei DNA damage and apoptosis of HeLa cells. Remarkably, TUNEL assay carried out to detect nuclei DNA damage showed 52% TUNEL-positive cells after treatment with a physiological concentration of β-cryptoxanthin (1.0 μM), which validates its potential as an anticancer drug of natural origin.
Highlights
IntroductionDietary intake of fruits and vegetables that are rich in bioactive carotenoids and other antioxidant phytochemicals (e.g., polyphenols, terpenoids, and isothiocyanantes) is associated with lower risk of chronic conditions and diseases, such as age-related macular degeneration, cardiovascular diseases (CVD), diabetes, neurodegenerative disorders, and several types of cancer [1,2,3,4,5,6,7]
Dietary intake of fruits and vegetables that are rich in bioactive carotenoids and other antioxidant phytochemicals is associated with lower risk of chronic conditions and diseases, such as age-related macular degeneration, cardiovascular diseases (CVD), diabetes, neurodegenerative disorders, and several types of cancer [1,2,3,4,5,6,7]
human cervical carcinoma (HeLa) and MDCK cells at a concentration of 1.5 × 105 cells/mL were separately cultured in a 96-well plate, and incubated under 5% CO2 for 12 h at 37 ◦ C
Summary
Dietary intake of fruits and vegetables that are rich in bioactive carotenoids and other antioxidant phytochemicals (e.g., polyphenols, terpenoids, and isothiocyanantes) is associated with lower risk of chronic conditions and diseases, such as age-related macular degeneration, cardiovascular diseases (CVD), diabetes, neurodegenerative disorders, and several types of cancer [1,2,3,4,5,6,7]. The efforts to discover phytochemicals-based chemopreventive and chemotherapy drugs for cervical cancer and other types of cancer have been increasing in recent years [3]. In this regard, several antioxidant phytochemicals, including carotenoids, have shown promising results of pro-apoptotic, anti-proliferative, anti-metastatic, and anti-angiogenic effects on various cancer types [9]. Several xanthophylls, including 9-Z-neoxanthin, showed potent and selective cytotoxic effects against HeLa cells, with IC50 values of just 3.8 μM [11]
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