PRESENTED BY

Arpitha .B. V
2nd M.Sc Biochemistry GUIDED BY
Dr. Pavitra K
DOS in Biochemistry
 CONTENTS

• Introduction
• Materials and methods
• Results and discussion
• Conclusion
 INTRODUCTION
• Many human cancers exhibit multidrug
resistance(MDR).
• MDR tumors are cross resistant to variety of
structurally unrelated cytotoxic drugs.
• One of the reason for MDR is MDR-linked
transporters , one such is p-glycoprotein
transporter(MDR1).
• This MDR linked p-gp transports any
xenobiotic as a substrate out of the cell via
ATP dependent mechanism.
Continued
MATERIALS AND METHODS

• Cell culture
• MTT assay
• Gamma-H2AX assay
• Western blot
• Immunohistochemistry
• Transcriptional analysis of NFkB expression
• Animals and tumor xenograft experiments
 RESULTS AND DISCUSSION
• Cytotoxicity evaluation using MTT assay
Continued
 Continued
Compound KB KB ChR8-5

IC50 ± S.E.M.α (μM) FRb IC50 ± S.E.M.α (μΜ) FRb

Doxorubicin 0.11±0.03 [1.0] 5.12±0.10 [46.54]

+ FA (10 μM) 0.11±0.01 [0.9] 3.75±0.05 [34.09]

+ FA (20 μM) 0.10±0.01 [0.8] 2.13±0.03 [19.36]

+ FA (30 μM) 0.10±0.02 [0.8] 0.79±0.05 [7.18]

+ CsA (3 μM) 0.10±0.01 [0.8] 0.21±0.05 [1.90]

Vincristine 0.09±0.01 [1.0] 4.63±0.10 [51.44]

+ FA (10 μM) 0.09±0.01 [0.9] 3.51±0.05 [39.00]

+ FA (20 μM) 0.09±0.02 [0.8] 1.97±0.03 [21.88]

+ FA (30 μM) 0.08±0.01 [0.8] 0.76±0.05 [8.40]

+ CsA (3 μM) 0.08±0.01 [0.8] 0.09±0.03 [1.00]

Impact of ferulic acid on DSB
formation
Effect of ferulic acid on the expression
apoptotic markers
Effect of ferulic acid on p-gp
expression
Continued
Effect of ferulic acid on NFkB
expression
Continued
Effect of ferulic acid on PI3K and AKT
expression
Effect of ferulic acid and doxorubicin in
KBChR 8-5 xenograft tumor model
Continued
CONCLUSION
Thank you