title: Luteolin enhances paclitaxel-induced apoptosis in human breast cancer MDA-MB-231 cells by blocking STAT3.
abstract: The potential use of low-dose chemotherapy has been appealing because lower dosages are more attainable during cancer therapy and cause less toxicity in patients. Combination therapy of paclitaxel, a promising frontline chemotherapy agent, with natural anti-tumor agents that are considerably less toxic and possess the capability of activating additional apoptotic signals may provide a rational molecular basis for novel chemotherapeutic strategies. Luteolin, a natural flavone, possesses multiple biological activities, including anti-tumor potential. In the present study, the effects of concomitant administration of luteolin and paclitaxel were investigated in human breast cancer MDA-MB-231 cells. Luteolin alone demonstrated an anti-proliferative effect. Co-administration of luteolin and paclitaxel resulted in an increase in apoptosis compared with the treatment of paclitaxel alone as evidenced by the results of a diamidino-2-phenylindole (DAPI) stain and Annexin-V-based assay. Moreover, immunoblotting analysis also showed that the co-administration of luteolin and paclitaxel activated caspase-8 and caspase-3 and increased the expression of Fas. Furthermore, the increased expression of Fas due to co-administration was shown to be due to the blocking of signal transducer and activator of transcription 3 (STAT3). Finally, combination therapy with luteolin and paclitaxel significantly reduced tumor size and tumor weight in an orthotopic tumor model of MDA-MB-231 cells in nude mice. These results suggest that the luteolin-paclitaxel combination could be a novel strategy for the treatment of breast cancer.
authors: Institute of Biochemistry and Biotechnology, Chung Shan Medical University, No. 110, Section 1, Chien-Kuo N. Road, Taichung, Taiwan.
authors: Mon-Yuan
authors: MY
authors: Yang
authors: Institute of Biochemistry and Biotechnology, Chung Shan Medical University, No. 110, Section 1, Chien-Kuo N. Road, Taichung, Taiwan; Department of Medical Education, Chung Shan Medical University Hospital, No. 110, Section 1, Chien-Kuo N. Road, Taichung 402, Taiwan.
authors: Chau-Jong
authors: CJ
authors: Wang
authors: School of Applied Chemistry, Chung Shan Medical University, No. 110, Section 1, Chien-Kuo N. Road, Taichung 402, Taiwan.
authors: Nai-Fang
authors: NF
authors: Chen
authors: Department of Anatomy, School of Medicine, Chung Shan Medical University, No. 110, Section 1, Chien-Kuo N. Road, Taichung, Taiwan.
authors: Wen-Hsin
authors: WH
authors: Ho
authors: School of Applied Chemistry, Chung Shan Medical University, No. 110, Section 1, Chien-Kuo N. Road, Taichung 402, Taiwan.
authors: Fung-Jou
authors: FJ
authors: Lu
authors: School of Applied Chemistry, Chung Shan Medical University, No. 110, Section 1, Chien-Kuo N. Road, Taichung 402, Taiwan; Department of Medical Education, Chung Shan Medical University Hospital, No. 110, Section 1, Chien-Kuo N. Road, Taichung 402, Taiwan. Electronic address: tht@csmu.edu.tw.
authors: Tsui-Hwa
authors: TH
authors: Tseng
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D047311:Luteolin / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008819:Mice, Nude; D017239:Paclitaxel / Q000494:pharmacology* / Q000627:therapeutic use; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors*
chemical_list: D050796:STAT3 Transcription Factor; D047311:Luteolin; D017239:Paclitaxel
keywords: Apoptosis; Fas; Luteolin; Paclitaxel; STAT3