Radiotherapy is a powerful tool in the treatment of cancer that has the advantage of preserving normal tissues. However, tumor radioresistance currently remains a major impediment to effective RT. Thus, exploring effective radiation sensitizers is urgently needed. In this study, we have shown that diosmetin, the aglycone of the lavonoid glycoside from olive leaves, citrus fruits and some medicinal herbs, has a promising effect on radiotherapy sensitization. In our results, DIO could induce G1 phase arrest and thus enhance the radiosensitivity of radioresistant A549/IR lung cancer cells. Furthermore, DIO also restrains the IR-induced DNA damage repair by inhibiting the activated Akt signaling pathway. The combination of Akt inhibition (DIO, LY294002 or MK-2206) and radiation potently blocked A549/IR cancer cell proliferation. In summary, these observations suggest that the natural compound DIO could act as a potential drug for the treatment of radioresistant lung cancer cells.

No abstract

Aloperine (ALO), an isolated alkaloid from the leaves of Sophora alopecuroides (S. alopecuroides), has been suggested to exhibit anti-inflammatory and antitumor properties, and has been traditionally used to treat various diseases, including cancers. However, little is known about the effects of ALO on the radio-sensitivity of lung cancer cells. In the present study, we confirmed that agent ALO inhibits cell growth, promotes cell aopotosis and induces G1 phase arrest and consequently enhanced the radio-sensitivity in radio-resistant lung cancer cells A549/IR. Mechanically, ALO markedly down-regulates the G1/S transition regulators, CDK4/6 and cyclin D1. Moreover, ALO decreases cell autophagy signaling, which is characterized by downregulated Beclin1 and upregulated p62, two key autophagy-associated proteins. We also observed that autophagy inhibitors, bafilomycin A1 (BafA) and chloroquine (CQ), could sensitize the radio-resistant cells to the ionizing radiation (IR) treatment, which is similar to the effect of ALO. Taken together, the findings from the present study suggest that inhibition of cell autophagy by ALO shows marked results in radio-resistant lung cancer cells, and is shown to enhance the effect of IR.