Biol. Pharm. Bull. 28(1) 69—77 (2005)

نویسندگان

  • Ganesh Chandra
  • Venkatasubbaiah Ashoka Kumar
چکیده

and normal tissues. The nature and extent of such effects, however, depend on selected biological parameter (e.g., oxygen supply, cell cycle) and can be modified by chemical agents such as radiosensitizers, radioprotectors and chemotherapeutic agents. A precise control of the mode of action of the radiation is important in order to achieve the maximum effect on tumor tissue, while minimizing the effect on normal tissue. The concept of an optimal irradiation dose providing a maximally positive response of the target tissue and minimal toxicity to the perilesional area is the basis of various fractionation schedules for the radiotherapeutic treatment of tumors. The combination therapy of treatment of tumors with radiation and different anticancer drugs like 5-fluorouracil, mitomycin C, etoposide and carboplatin have been tried clinically. However, the side effects of such modes of treatment are severe and have resulted in the occurrence of secondary malignancies. Some agents under test are interferon beta that has cytotoxic synergism with radiation against MO59J cell line in vitro, and MDM2 inhibitors, such as antisense oligonucleotides as radiosensitizer against various neoplastic cell lines in vitro and different tumor xenografts in vivo. Nevertheless efforts to explore better radiosensitizers shall be continued to reduce toxic side effects of combination treatment. The effect of radiation on tumor tissue can be optimized by adding radiosensitizing agents, in order to achieve a greater degree of tumor damage than expected from the additive effect of each modality. Most of the known and routinely used radiosensitizers are neither selective nor tumor specific. Such compounds are commonly toxic per se and thus lead to severe systemic side effects. In addition, local failure is still commonly observed even with the application of radiosensitizers and local tumor regrowth may occur in 60 to 80% of cancer patients at the time of death. Herbs offer a vast source of new chemicals and some of them are structurally so complex that they can not be synthesized even with the advanced technology at our disposal. The herbal drugs have gained attention and popularity because of their negligible toxicity and possibly with a ray of hope that they may replace some of the available antineoplastic drugs that are highly toxic. 7-Beta-hydroxycholesterol, a natural oxysterol has been shown to posses marked antiproliferative and cytotoxic activities and demonstrated enhanced radiosensitivity of RDM4 cells. Certain herbal preparations from plants like Withania somnifera have also been reported to show a marked tumor inhibitory activity in vitro, against cells derived from human carcinoma of the nasopharynx and experimental tumors. It has also been reported to enhance the effect of radiation in mice. Plumbagin, derived from the plant Plumbago zeylanica, has been reported to enhance the effect of radiation in mice bearing sarcoma S180 and Ehrlich ascites carcinoma. Aphanamixis polystachya WALL & PARKER (Amoora rohituka (RoXB.) WIGHT & ARN. is distributed throughout India in evergreen forests and is a member of the family Meliaceae. It has been reported to posses several medicinal properties against various ailments including spleen, liver tumors and Friend’s leukemia. Our earlier experiments have shown that the alcoholic fraction of the stem bark of Aphanamixis polystachya (APE) possess anticancer activity against the Ehrlich ascites carcinoma transplanted in mice (data not shown). However, the radiosensitizing effect of APE has not been studied. Therefore, the present investigation was undertaken to study the radiosensitizing effect of APE in mice transplanted with Ehrlich ascites carcinoma and exposed to different doses of g-radiation. January 2005 Biol. Pharm. Bull. 28(1) 69—77 (2005) 69

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تاریخ انتشار 2004