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Anticancer Efficacy of Photodynamic Therapy with Lung Cancer-Targeted Nanoparticles
Published on: December 1, 2016
Enhancement of docetaxel anticancer activity by a novel diindolylmethane compound in human non-small cell lung cancer
Nkechi Ichite1, Mahavir B Chougule, Tanise Jackson
1College of Pharmacy and Pharmaceutical Sciences. Florida A&M University, Tallahassee, Florida 32307, USA.
Purpose:
This study was conducted to examine the cytotoxic effects of a peroxisome proliferator-activated receptor gamma (PPARgamma) agonist, 1,1-bis (3'-indolyl)-1-(p-biphenyl) methane (DIM-C-pPhC(6)H(5)), alone and in combination with docetaxel in vitro in A549 lung cancer cells and in vivo in nude mice bearing A549 orthotopic lung tumors.
Experimental Design:
Isobolographic method was used to calculate combination index values from cell viability data. Apoptosis was evaluated in A549 cells by terminal deoxynucleotidyl transferase-mediated nick end labeling assay and measurement of cleaved poly(ADP-ribose) polymerase level. Expression of proteins was studied by Western blotting. A549 cells were implanted to induce orthotopic lung tumors in nude mice and the efficacy of docetaxel, DIM-C-pPhC(6)H(5), or combination was determined. Apoptosis and cleaved caspase-3 expression in the harvested tissues were studied by terminal deoxynucleotidyl transferase-mediated nick end labeling and immunohistochemistry, respectively.
Results:
The combination index values (0.36-0.9) suggested synergistic to additive effects of docetaxel + DIM-C-pPhC(6)H(5) and resulted in the highest increase in percentage of apoptotic cells and expression of cleaved poly(ADP-ribose) polymerase, Bax, and N-cadherin compared with treatment with either agent. The combination also enhanced procaspase-3 and -9 cleavage. In vivo, docetaxel + DIM-C-pPhC(6)H(5) reduced lung weights by 57% compared with 39% by docetaxel or 22% by DIM-C-pPhC(6)H(5) alone, induced apoptosis in 43% of the tumor cells compared with 29% and 22% in tumors treated with docetaxel and DIM-C-pPhC(6)H(5), respectively, and increased procaspase-3 cleavage compared with either agent alone.
Conclusions:
These findings suggest potential benefit for use of docetaxel and DIM-C-pPhC(6)H(5) combination in lung cancer treatment.
Insights
The combination of docetaxel and DIM-C-pPhC(6)H(5) shows synergistic effects against lung cancer cells. This combination therapy enhances apoptosis and reduces tumor growth in vivo, suggesting potential for lung cancer treatment.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Lung cancer remains a leading cause of cancer-related mortality worldwide.
- Novel therapeutic strategies are crucial for improving patient outcomes.
- Targeting cellular pathways involved in cancer progression is a key area of research.
Purpose of the Study:
- To investigate the cytotoxic effects of a PPARgamma agonist, DIM-C-pPhC(6)H(5), alone and in combination with docetaxel.
- To evaluate the efficacy of this combination in vitro using A549 lung cancer cells.
- To assess the in vivo efficacy in nude mice bearing A549 orthotopic lung tumors.
Main Methods:
- Isobolographic analysis to determine drug interactions (combination index).
- Assays for apoptosis (TUNEL, cleaved PARP, cleaved caspase-3) and protein expression (Western blotting).
- In vivo studies using orthotopic lung tumor models in nude mice.
Main Results:
- The combination of docetaxel and DIM-C-pPhC(6)H(5) demonstrated synergistic to additive effects (Combination Index: 0.36-0.9).
- Combination treatment significantly increased apoptosis and cleaved PARP levels in vitro and in vivo.
- In vivo, the combination reduced tumor weight and enhanced apoptosis more effectively than either agent alone.
Conclusions:
- Docetaxel and DIM-C-pPhC(6)H(5) combination exhibits significant anti-cancer activity in lung cancer models.
- The synergistic interaction enhances apoptosis and tumor growth inhibition.
- This combination holds promise as a potential therapeutic strategy for lung cancer treatment.
