Abstract：
:Combretastatin A-4 exhibits efficient anti-cancer potential in human tumors, including multidrug-resistant tumors. We evaluated the mutagenic, apoptotic and immunomodulatory potential of two diaryl sulfide analogs of combretastatin A-4, 1,2,3-trimethoxy-5-([4-methoxy-3-nitrophenyl]thio)benzene (analog 1) and 1,2,3-trimethoxy-5-([3-amino-4-methoxyphenyl]thio)benzene (analog 2), as well as their association with the anti-tumor agent cyclophosphamide, in Swiss mice. Such evaluation was achieved using the comet assay, peripheral blood micronucleus test, splenic phagocytosis assay, and apoptosis assay. Both analogs were found to be genotoxic, mutagenic and to induce apoptosis. They also increased splenic phagocytosis, although this increase was more pronounced for analog 2. When combined with cyclophosphamide, analog 1 enhanced the mutagenic and apoptotic effects of this anti-tumor agent. In contrast, analog 2 did not enhance the effects of cyclophosphamide and prevented apoptosis at lower doses. These data suggest that analog 1 could be an adjuvant chemotherapeutic agent and possibly improve the anti-neoplastic effect of cyclophosphamide. Additionally, this compound could be a candidate chemotherapeutic agent and/or an adjuvant for use in combined anti-cancer therapy.
journal_name
Environ Toxicol Pharmacoljournal_title
Environmental toxicology and pharmacologyauthors
Carvalho PC,Santos EA,Schneider BU,Matuo R,Pesarini JR,Cunha-Laura AL,Monreal AC,Lima DP,Antoniolli AC,Oliveira RJdoi
10.1016/j.etap.2015.08.028subject
Has Abstractpub_date
2015-11-01 00:00:00pages
715-21issue
3eissn
1382-6689issn
1872-7077pii
S1382-6689(15)30074-0journal_volume
40pub_type
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