The selective effect of genistein on the toxicity of bleomycin in normal lymphocytes and HL-60 cells

Lee, Rami; Kim, Yang Jee; Lee, Young Joon; Chung, Hai Won

doi:10.1016/j.tox.2003.08.011

Cited by 37 publications

(13 citation statements)

References 26 publications

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“…Similar observations has been reported by other investigators showing that the antitumor effects of chemotherapeutics, including 5-fluorouracil (5-FU), adriamycin, cytosine arabinoside, tamoxifen and perifosine could be potentiated by genistein [84;122-126]. Genistein also enhanced the antitumor effect of bleomycin in HL-60 cells, but not in normal lymphocytes in an in vitro study [127]. The synergistic action of genistein and cisplatin or carmustine (BCNU) on the growth inhibition of glioblastoma and medulloblastoma cells has also been observed [128].…”

Section: The Sensitizing Effect Of Genistein In Cancer Treatmentsupporting

confidence: 86%

Multi-targeted therapy of cancer by genistein

Banerjee¹,

Li²,

Wang³

et al. 2008

Cancer Letters

560

383

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Soy isoflavones have been identified as dietary components having an important role in reducing the incidence of breast and prostate cancers in Asian countries. Genistein, the predominant isoflavone found in soy products, has been shown to inhibit the carcinogenesis in animal models. There is a growing body of experimental evidence showing that the inhibition of human cancer cell growth by genisteinis mediated via the modulation of genes that are related to the control of cell cycle and apoptosis. It has been shown that genistein inhibits the activation of NF-κB and Akt signaling pathways, both of which are known to maintain a homeostatic balance between cell survival and apoptosis. Moreover, genistein antagonizes estrogen-and androgen-mediated signaling pathways in the processes of carcinogenesis. Furthermore, genistein has been found to have antioxidant properties, and shown to be a potent inhibitor of angiogenesis and metastasis. Taken together, both in vivo and in vitro studies have clearly shown that genistein, one of the major soy isoflavones, is a promising agent for cancer chemoprevention and further suggest that it could be an adjunct to cancer therapy by virtue of its effects on reversing radioresistance and chemoresistance. In this review, we attempt to provide evidence for these preventive and therapeutic effects of genistein in a succinct manner highlighting comprehensive state-of-the-art knowledge regarding its multi-targeted biological and molecular effects in cancer cells.

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Section: The Sensitizing Effect Of Genistein In Cancer Treatmentsupporting

confidence: 86%

Multi-targeted therapy of cancer by genistein

Banerjee¹,

Li²,

Wang³

et al. 2008

Cancer Letters

560

383

View full text Add to dashboard Cite

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“…Similarly, WR-2721 and genstein have been reported to protect bleomycin-induced DNA damage in the normal lymphocytes but not in tumor cells (Buschini et al, 2002). An identical effect has been observed with vitamin E ((+)-alpha-tocopherol) against the DNA damage induced by bleomycin (Wozniak et al, 2004;Lee et al, 2004). Similarly (−)-epigallocatechin-3-gallate (EGCG) has been reported to protect against bleomycininduced DNA damage in human leukocytes (Glei and Pool-Zobel, 2006).…”

Section: Discussionmentioning

confidence: 68%

Naringin, a grapefruit flavanone, protects V79 cells against the bleomycin‐induced genotoxicity and decline in survival

Jagetia

Jha

2006

J of Applied Toxicology

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The effect of naringin, a grapefruit flavonone was studied on bleomycin-induced genomic damage and alteration in the survival of cultured V79 cells. Exposure of V79 cells to bleomycin induced a concentration dependent elevation in the frequency of binucleate cells bearing micronuclei (MNBNC) and a maximum number of MNBNCs were observed in the cells treated with 50 microg ml(-1) bleomycin, the highest concentration evaluated. This genotoxic effect of bleomycin was reflected in the cell survival, where a concentration dependent decline was observed in the cells treated with different concentrations of bleomycin. Treatment of cells with 1 mm naringin before exposure to different concentrations of bleomycin arrested the bleomycin-induced decline in the cell survival accompanied by a significant reduction in the frequency of micronuclei when compared with bleomycin treatment alone. The cell survival and micronuclei induction were found to be inversely correlated. The repair kinetics of DNA damage induced by bleomycin was evaluated by exposing the cells to 10 microg ml(-1) bleomycin using single cell gel electrophoresis. Treatment of V79 cells with bleomycin resulted in a continuous increase in DNA damage up to 6 h post-bleomycin treatment as evident by migration of more DNA into the tails (% tail DNA) of the comets and a subsequent increase in olive tail moment (OTM), an index of DNA damage. Treatment of V79 cells with 1 mm naringin reduced bleomycin-induced DNA damage and accelerated DNA repair as indicated by a reduction in % tail DNA and OTM with increasing assessment time. A maximum reduction in the DNA damage was observed at 6 h post-bleomycin treatment, where it was 5 times lower than bleomycin alone. Our study, which was conducted on the basis of antioxidant, free radical scavenging and metal chelating properties of naringin demonstrates that naringin reduced the genotoxic effects of bleomycin and consequently increased the cell survival and therefore may act as a chemoprotective agent in clinical situations.

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“…Another part of our proposed hypothesis is that propolis and their flavonoids compounds in combination with standard tumor therapeutic agents may reduce the toxicity of Table 3 The effect of WSDP, EEP, naringenin, or quercetin alone and/or in combination with irinotecan on hematological parameters in tumor bearing mice Experimental The value was significantly different (P \ 0.05) from the corresponding value of irinotecan-treated animals analyzed by Student's t-test Table 4 The chemotherapeutic agent (irinotecan) on normal cells. Several studies using animal models also support this part of the hypothesis [13][14][15]. Our previous work [5] has shown that WSDP, EEP, naringin, and quercetin given in combination with chemotherapeutic agent irinotecan delayed Ehrlich ascites tumor (EAT) growth and increased life span of EATbearing mice.…”

Section: Discussionmentioning

confidence: 81%

Protective effects of propolis and related polyphenolic/flavonoid compounds against toxicity induced by irinotecan

et al. 2009

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Despite the excellent chemotherapeutic effect of irinotecan, its cytotoxicity and genotoxicity in normal cells remains a major problem in chemotherapy. This study was carried out to find whether propolis preparations and related flavonoids (quercetin, naringin) might enhance irinotecan-induced cytotoxicity to tumor cells in mice bearing Ehrlich ascites tumors (EAT) while protecting normal blood, liver, and kidney cells. The preparation of propolis and their flavonoids were given to mice intraperitoneally at a dose of 100 mg kg(-1) body weight for three consecutive days before the ip injection of EAT cells (2×10(6)). Irinotecan was administered ip at dose of 50 mg kg(-1) on days 3, 4, and 5 after tumor cell inoculation. The combination treatment resulted in substantial inhibition of the growth of EAT cells as well as treatment with quercetin or irinotecan alone, whereas other treatment by itself showed little effect. However, when mice were pre-treated with test components prior to irinotecan, the frequencies of irinotecan-induced micronuclei (MN) was decreased but in mice bearing tumor QU and EEP increased number of micronucleated cells. Propolis preparation and related flavonoids were found to exhibit an important immunomodulatory effect and could decrease irinotecan-induced toxic and genotoxic effects to normal cells without effecting irinotecan cytotoxicity in EAT cells.

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The selective effect of genistein on the toxicity of bleomycin in normal lymphocytes and HL-60 cells

Cited by 37 publications

References 26 publications

Multi-targeted therapy of cancer by genistein

Multi-targeted therapy of cancer by genistein

Naringin, a grapefruit flavanone, protects V79 cells against the bleomycin‐induced genotoxicity and decline in survival

Protective effects of propolis and related polyphenolic/flavonoid compounds against toxicity induced by irinotecan

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