In Vitro and In Vivo Efficacy of Photofrin® and Pheophorbide a, a Bacteriochlorin, in Photodynamic Therapy of Colonic Cancer Cells¶

2002 ◽  
Vol 75 (2) ◽  
pp. 140 ◽  
Author(s):  
A. Hajri ◽  
S. Wack ◽  
C. Meyer ◽  
M. K. Smith ◽  
C. Leberquier ◽  
...  
2021 ◽  
Vol 22 (22) ◽  
pp. 12502
Author(s):  
Shoji Kokubo ◽  
Shinobu Ohnuma ◽  
Megumi Murakami ◽  
Haruhisa Kikuchi ◽  
Shota Funayama ◽  
...  

The ATP-binding cassette subfamily G member 2 (ABCG2) transporter is involved in the development of multidrug resistance in cancer patients. Many inhibitors of ABCG2 have been reported to enhance the chemosensitivity of cancer cells. However, none of these inhibitors are being used clinically. The aim of this study was to identify novel ABCG2 inhibitors by high-throughput screening of a chemical library. Among the 5812 compounds in the library, 23 compounds were selected in the first screening, using a fluorescent plate reader-based pheophorbide a (PhA) efflux assay. Thereafter, to validate these compounds, a flow cytometry-based PhA efflux assay was performed and 16 compounds were identified as potential inhibitors. A cytotoxic assay was then performed to assess the effect these 16 compounds had on ABCG2-mediated chemosensitivity. We found that the phenylfurocoumarin derivative (R)-9-(3,4-dimethoxyphenyl)-4-((3,3-dimethyloxiran-2-yl)methoxy)-7H-furo [3,2-g]chromen-7-one (PFC) significantly decreased the IC50 of SN-38 in HCT-116/BCRP colon cancer cells. In addition, PFC stimulated ABCG2-mediated ATP hydrolysis, suggesting that this compound interacts with the substrate-binding site of ABCG2. Furthermore, PFC reversed the resistance to irinotecan without causing toxicity in the ABCG2-overexpressing HCT-116/BCRP cell xenograft mouse model. In conclusion, PFC is a novel inhibitor of ABCG2 and has promise as a therapeutic to overcome ABCG2-mediated MDR, to improve the efficiency of cancer chemotherapy.


Author(s):  
Ivan Mfouo Tynga ◽  
Heidi Abrahamse

Deregulation of cell growth and development lead to cancer, a severe condition that claims millions of lives worldwide. Targeted or selective approaches used during cancer treatment determine the efficacy and outcome of the therapy. In order to enhance specificity and targeting and better treatment options for cancer, novel and alternative modalities are currently under development. Photodynamic therapy has the potential to eradicate cancer and combination therapy would yield even greater outcomes. Nanomedicine-aided cancer therapy shows enhanced specificity for cancer cells and minimal side-effects coupled with effective cancer destruction both in vitro and in vivo. Nanocarriers used in drug-delivery systems are well able to penetrate cancer stem cell niche, simultaneously killing cancer cells and eradicate drug-resistant cancer stem cells, yielding therapeutic efficiency up to 100 fold against drug-resistant cancer in comparison with free drugs. Safety precautions should be considered when using Nano-mediated therapy as the effects of extended exposure to biological environments are still to be determined.


2011 ◽  
Vol 29 (3) ◽  
pp. 155-160 ◽  
Author(s):  
Ruifeng Ge ◽  
Jin-Chul Ahn ◽  
Jang-In Shin ◽  
Chan Woong Bahk ◽  
Peijie He ◽  
...  

2014 ◽  
Vol 11 (3) ◽  
pp. 426-433
Author(s):  
Margarete K. Akens ◽  
Lisa Wise-Milestone ◽  
Emily Won ◽  
Joerg Schwock ◽  
Albert J.M. Yee ◽  
...  

Nanomaterials ◽  
2018 ◽  
Vol 8 (11) ◽  
pp. 923 ◽  
Author(s):  
Ivan Mfouo Tynga ◽  
Heidi Abrahamse

Deregulation of cell growth and development lead to cancer, a severe condition that claims millions of lives worldwide. Targeted or selective approaches used during cancer treatment determine the efficacy and outcome of the therapy. In order to enhance specificity and targeting and obtain better treatment options for cancer, novel modalities are currently under development. Photodynamic therapy has the potential to eradicate cancer, and combination therapy would yield even greater outcomes. Nanomedicine-aided cancer therapy shows enhanced specificity for cancer cells and minimal side-effects coupled with effective cancer destruction both in vitro and in vivo. Nanocarriers used in drug-delivery systems are very capable of penetrating the cancer stem cell niche, simultaneously killing cancer cells and eradicating drug-resistant cancer stem cells, yielding therapeutic efficiency of up to 100-fold against drug-resistant cancer in comparison with free drugs. Safety precautions should be considered when using nano-mediated therapy as the effects of extended exposure to biological environments are still to be determined.


1991 ◽  
Vol 11 (2) ◽  
pp. 174-182 ◽  
Author(s):  
Takashi Yano ◽  
Tohru Uozumi ◽  
Keiichi Kawamoto ◽  
Kazutoshi Mukada ◽  
Jun Onda ◽  
...  

2011 ◽  
Vol 26 (5) ◽  
pp. 734-742 ◽  
Author(s):  
Sandy Wan-Heng Hoi ◽  
Hoi Ming Wong ◽  
Judy Yuet-Wa Chan ◽  
Grace Gar Lee Yue ◽  
Gary Man-Kit Tse ◽  
...  

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1399
Author(s):  
Ben Chung Lap Chan ◽  
Priyanga Dharmaratne ◽  
Baiyan Wang ◽  
Kit Man Lau ◽  
Ching Ching Lee ◽  
...  

High prevalence rates of methicillin-resistant Staphylococcus aureus (MRSA) and lack of effective antibacterial treatments urge discovery of alternative therapeutic modalities. The advent of antibacterial photodynamic therapy (aPDT) is a promising alternative, composing rapid, nonselective cell destruction without generating resistance. We used a panel of clinically relevant MRSA to evaluate hypericin (Hy) and pheophobide a (Pa)-mediated PDT with clinically approved methylene blue (MB). We translated the promising in vitro anti-MRSA activity of selected compounds to a full-thick MRSA wound infection model in mice (in vivo) and the interaction of aPDT innate immune system (cytotoxicity towards neutrophils). Hy-PDT consistently displayed lower minimum bactericidal concentration (MBC) values (0.625–10 µM) against ATCC RN4220/pUL5054 and a whole panel of community-associated (CA)-MRSA compared to Pa or MB. Interestingly, Pa-PDT and Hy-PDT topical application demonstrated encouraging in vivo anti-MRSA activity (>1 log10 CFU reduction). Furthermore, histological analysis showed wound healing via re-epithelization was best in the Hy-PDT group. Importantly, the dark toxicity of Hy was significantly lower (p < 0.05) on neutrophils compared to Pa or MB. Overall, Hy-mediated PDT is a promising alternative to treat MRSA wound infections, and further rigorous mechanistic studies are warranted.


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