期刊
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
卷 64, 期 12, 页码 2541-2548出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jafc.5b05343
关键词
Monascus; rubropunctatin; chemotherapy; phototherapy
资金
- National Natural Science Foundation of China [J1103303]
- Natural Science Foundation of Fujian Province of China [2012J05155]
- Marine Public Welfare Research Project of China [201205022]
- Technology Development Foundation of Fuzhou University [2011-XY-7, 2013-XQ-9]
The Monascus pigment, rubropunctatin, was extracted and purified from red mold rice (RMR), and its cytatoxic activities against human cervical carcinoma HeLa cells were studied under the conditions with or without light irradiation. The IC50 value of rubropunctatin against HeLa cells in the dark was 93.71 +/- 1.96 mu M (24 h), while the cytotoxic activity was enhanced more than 3 times (IC50 = 24.02 +/- 2.17 mu M) under light irradiation (halogen lamp, 500 W; wavelength, 597-622 nm; and fluence rate, 15 mW cm(-2), for 30 min). However, the IC50 value of rubropunctatin against the immortalized human cervical epithelial H8 cells was more than 300 mu M, even under light irradiation, indicating that rubropunctatin has a favorable selectivity index (SI). Treatment of HeLa cells with rubropunctatin in the dark or under light irradiation resulted in a dose-dependent apoptosis, as validated by the increase in the percentage of cells in the sub-G1 phase and phosphatidylserine externalization; and the inductive effect on HeLa cell apoptosis was boosted by the light irradiation. In addition, treatment with rubropunctatin alone or under light irradiation was found to induce apoptosis in HeLa cells via the mitochondrial pathway, including loss of mitochondrial membrane potential, activation of caspase-3, caspase-8, and caspase-9, and increase of the level of intracellular reactive oxygen species (ROS). It was suggested that rubropunctatin could be a promising natural dual anticancer agent for photodynamic therapy and chemotherapy.
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