Ferulic acid reverses ABCB1-mediated paclitaxel resistance in MDR cell lines.
Multidrug resistance (MDR) remains a major obstacle in cancer chemotherapy. The use of the dietary phytochemicals as chemosensitizing agents to enhance the efficacy of conventional cytostatic drugs has recently gained the attention as a plausible approach for overcoming the drug resistance. The aim of this study was to investigate whether a naturally occurring diet-based phenolic acid, ferulic acid, could sensitize paclitaxel efficacy in ABCB1 overexpressing (P-glycoprotein) colchicine selected KB Ch(R)8-5 cell line. In vitro drug efflux assays demonstrated that ferulic acid inhibits P-glycoprotein transport function in drug resistant KB Ch(R)8-5 cell lines. However, ferulic acid significantly downregulates ABCB1 expression in a concentration dependent manner. Cytotoxicity assay reveals that ferulic acid decreased paclitaxel resistance in KBCh(R)8-5 and HEK293/ABCB1 cells, which indicates its chemosensitizing potential. Clonogenic cell survival assay and apoptotic morphological staining further confirm the chemosensitizing potential of ferulic acid in drug resistant KB Ch(R)8-5 cell lines. Ferulic acid treatment enhances paclitaxel mediated cell cycle arrest and upregulates paclitaxel-induced apoptotic signaling in KB resistant cells. Hence, it has been concluded that downregulation of ABCB1 and subsequent induction of paclitaxel-mediated cell cycle arrest and apoptotic signaling may be the cause for the chemosensitizing potential of ferulic acid in P-gp overexpressing cell lines.
Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar 608002, Tamilnadu, India.
Ganesan
G
Muthusamy
Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar 608002, Tamilnadu, India.
Agilan
A
Balupillai
Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar 608002, Tamilnadu, India.
Karthikeyan
K
Ramasamy
Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar 608002, Tamilnadu, India.
Mohana
M
Shanmugam
Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar 608002, Tamilnadu, India.
Srithar
S
Gunaseelan
Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar 608002, Tamilnadu, India.
Beaulah
B
Mary
Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar 608002, Tamilnadu, India. Electronic address: drprasadnr@gmail.com.
N Rajendra
NR
Prasad
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003373:Coumaric Acids / Q000378:metabolism / Q000494:pharmacology*; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D005452:Fluoresceins / Q000378:metabolism; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007624:KB Cells; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D062105:Molecular Docking Simulation; D017239:Paclitaxel / Q000494:pharmacology*; D011487:Protein Conformation
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D003373:Coumaric Acids; D005452:Fluoresceins; C085925:calcein AM; C004999:ferulic acid; D017239:Paclitaxel
Apoptosis; Cell cycle; Ferulic acid; Multidrug resistance; P-glycoprotein; Paclitaxel