Etoposide cytotoxicity

Stuart NS, Philip P, Harris AL, et al. High-dose tamoxifen as an enhancer of etoposide cytotoxicity. Clinical effects and in vitro assessment in p-glycoprotein expressing cell lines. Br J Cancer 1992 66(5) 833-839. 

DNAS1L3 Is Required for Etoposide-induced Internucleosomal DNA Fragmentation and Increases Etoposide Cytotoxic in Transfected Osteosarcoma Cells... 

Examples of inhibitors of chromatin function derived from flowering plants (Fig. 80) are etoposide (lignan) and alkaloids camptothecin, Vinca alkaloids, and 7 epitaxol. The rhizome of Podophyllum peltatum L. (May apple, Berberidaceae) has been used to remove warts and to relieve the bowels from costiveness since very early times. It contains podophyllo-toxin, a cytotoxic lignan from which etoposide (Vepesid ), which is used to treat lung cancer, lymphomas, and leukemias on account of its ability to inhibit the activity of... 

Etoposide and teniposide are synthetic derivatives of the extract of the American mandragora plant (May Apple). The mechanism of their action has not been completely explained however, they act on the enzyme topoisomerase II, which disturbs the twisting of DNA. In addition, they inhibit DNA and RNA synthesis, as well as transport of nucleotides to cells. Cytotoxic action on normal cells is observed only in very high doses. These drugs exhibit significant activity in lymphomas, leukemia, Kaposi s sarcomas, and in testicular cancer. 

Etoposide and teniposide derivatives Lundberg (1994) Enhanced solubilization, cellular uptake, and cytotoxic activity of lipophilic prodrugs... 

P-Carotene has been shown to enhance the cytotoxicity of melphalan and BCNU on human squamous carcinoma cells and of cisplatin and dacarbazine on melanoma cells. In mice with transplanted mammary carcinoma, P-carotene enhanced the antitumor effect of cyclophosphamide, and in mice transplanted with Fsall fibrosarcoma or SCC VII carcinoma, p-carotene enhanced the antitumor effect of melphalan, BCNU, doxorubicin, and etoposide. p-Carotene (5 to 50 mg/kg) has been shown to reduce the genotoxicity of cyclophosphamide in mice and of mitomycin C, methyl methanesulfonate, and bleomycin in cultured cells. P-Carotene also reduced the rate of tumor induction in animals receiving chronic low doses of cyclophosphamide. 

Rappa G, Shyam K, Lorico A et al (2000) Structure-activity studies of novobiocin analogs as modulators of the cytotoxicity of etoposide (VP-16). Oncol Res 12 113-119... 

Drugs used in cancer chemotherapy are cytotoxic drugs, hormones, plant derivatives, radioactive isotopes, and miscellaneous agents (e.g., procarbazine, hydroxyurea, mitotane). The plant-based drugs vincristine, vinblastine, vinorel-bine, etoposide, and campothecins. Radioactive isotopes, such as 131 iodine (131 I), are used in the treatment of thyroid tumors. Cytotoxic drugs (e.g., cis-platin, cyclophosphamide, 6-mercaptopurine, 5-fluorouracil, and methotrexate are used for the treatment of cancer. 

Kaufmann SH. Induction of endonucleolytic DNA cleavage in human acute myelogenous leukemia cells by etoposide, camptothecin, and other cytotoxic anticancer drugs A cautionary note. Cancer Res 1989 49 5870-5878. 

Cytotoxic chemotherapy is the cornerstone of therapy for metastatic testicular cancer. This type of cancer (known as a type of germ cell tumour as it is thought to be derived from cells in the germ cell lineage that are blocked in maturation) has been found to be extremely responsive to chemotherapeutic agents, in particular cisplatin and etoposide. There is no role for radiotherapy at this stage due to the advanced nature of the disease. 

Figure 3.1 Combined effects of a combination of 7 anticancer drugs with different sites of action. Shown are the predicted (solid line concentration addition, broken line independent action), and the observed (circles) cytotoxic effects on DU 145 prostate cancer cells. Doxorubicin, daunorubicin, vincristin, cis-platin, etoposide, melphalan and 5-fluorouracil were combined at equitoxic concentrations. The mixture effect predictions were derived from the concentration-response curves of the individual anticancer drugs...

Selected experimental agents were evaluated for cytotoxicity against KB cells using nasopharyngeal carcinoma cells and tested for stimulation of cellular protein-linked DNA breaks using etoposide as a positive control. Testing results are provided in Table 2. 

Black cohosh 2. Caffeine 3. Evening primrose oil 4. Scutellaria baicalensis 5. Starflower (borage) 1. Docetaxel 2. Paditaxel 3. Doxorubicin 4. Tamoxifen 5. Cisplatin 6. Vinorelbine t cytotoxic properties Unknown mechanism (black cohosh). Caffeine t cytotoxic effects of cisplatin wogonin present in Scutellaria enhances etoposide-induced apoptosis. Gamolenic acid found in evening primrose oil and borage potentiated the in vitro toxicity of paditaxel and vinorelbine, attributed to an unsaturated fatty acid as modulators of tumour cell chemosensitivity Be aware and avoid concomitant use... 

In 37 patients with HIV-associated non-Hodgkin s lymphoma who were treated with a 96-hour continuous intravenous infusion of cyclophosphamide + doxorubicin + etoposide, severe (grade 3 or 4) mucositis occurred in eight of 12 patients who received concomitant saquinavir (600 mg tds) compared with three of 25 who did not receive saquinavir. Although the authors did not measure saquinavir plasma concentrations, they suggested that this finding may have been explained by inhibition of the metabolism of one or more of the cytotoxic drugs by saquinavir (17). 

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