In vitro and in vivo studies of 5,7-dihydroxy flavones isolated from Alpinia galanga (L.) against human lung cancer and ascetic lymphoma
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Alpinia galanga (A. galanga) of Zingiberaceae family has been widely studied for their potential biological and medicinal properties. In this study, chrysin, isolated from A. galanga, was screened for the presence of the flavonoid compound 5,7-dihydroxyflavone. Chrysin was found to induce cytotoxicity and apoptosis in human lung cancer cells and murine lymphoma cells at 25, 50, and 75 µg/ml concentrations sparing the normal fibroblast cells and lymphocytes. Cell cycle analysis using flow cytometry showed that there was a dose-dependent increase of accumulation of the S-phase cells, causing a G1/S-phase arrest induced by chrysin at these concentrations. Annexin V- and active caspase-3-positive cells were found to increase dose dependently in these cells as evidenced by flow cytometry. The ascetic tumor reduction studies in Dalton’s lymphoma ascites mice models revealed that a dose of 1.3 mg/kg body weight of chrysin decreased the tumor volume significantly and increased the lifespan of mice to 52.6%. Moreover, the compound showed chemoprotective effects when administered along with cyclophosphamide, thereby reducing the toxic effects. These observations were confirmed using the evaluations of hematological parameters and liver and kidney function tests from animal studies. The synergistic interaction of chrysin with cyclophosphamide in terms of reducing the tumor size and increasing the lifespan of mice compared with the individual treatments suggests the possibility of reducing cyclophosphamide concentrations in the combination treatment.
KeywordsApoptosis Chemoprotection Chrysin Lung cancer Lymphoma
We would like to acknowledge Indian Council of Medical Research (ICMR), Government of India, No. 45/31/2006/BMS/TRM for financial support. We extend our sincere thanks to Scientists and staff of Regional cancer centre (RCC) and Central tuber crops research institute (CTCRI) and HLL Lifecare Limited, Thiruvananthapuram for the support and guidance, Dr. TR Santhosh Kumar, Scientist F for flow cytometry molecular platforms at Rajiv Gandhi Centre for Biotechnology (RGCB), Thiruvananthapuram and University of Kerala, Karyavattom, Thiruvananthapuram for spectral studies and Dr. K Sujathan, Associate Professor, Regional Cancer Centre, Thiruvananthapuram for histopathological studies.
The work was funded by Indian Council of Medical Research (ICMR), Government of India, Ref No. 45/31/2006/BMS/TRM.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All applicable International, National, and Institutional guidelines for the care of animals were followed as per Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), Government of India. (Ref No: IAEC/RCC/No.1/06 dated 29.07.06).
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