Additively Enhanced Antiproliferative Effect of Interferon Combined with Proanthocyanidin on Bladder Cancer Cells

Abstract

Although interferon (IFN) has been often used as immunotherapy for bladder cancer, its efficacy is rather unsatisfactory, demanding further improvement. Combination therapy is one of viable options, and grape seed proanthocyanidin (GSP) could be such an agent to be used with IFN because it has been shown to have anticancer activity. We thus investigated whether combination of IFN and GSP might enhance the overall antiproliferative effect on bladder cancer cells in vitro. Human bladder cancer T24 cells were employed and treated with the varying concentrations of recombinant IFN-α2b (0-100,000 IU/ml), GSP (0-100 μg/ml), or their combinations. IFN-α2b alone led to a ~50% growth reduction at 20,000 (20K) IU/ml, which further declined to ~67% at ≥50K IU/ml. Similarly, GSP alone induced a ~35% and ~100% growth reduction at 25 and ≥50 μg/ml, respectively. When IFN-α2b and GSP were then combined, combination of 50K IU/ml IFN-α2b and 25 μg/ml GSP resulted in a drastic >95% growth reduction. Cell cycle analysis indicated that such an enhanced growth inhibition was accompanied by a G1 cell cycle arrest. This was further confirmed by Western blot analysis revealing that expressions of G1-specific cell cycle regulators (CDK2, CDK4, cyclin E and p27/Kip1) were distinctly modulated with such IFN-α2b/GSP treatment. Therefore, these findings support the notion that combination of IFN-α2b and GSP is capable of additively enhancing antiproliferative effect on T24 cells with a G1 cell cycle arrest, implying an adjuvant therapeutic modality for superficial bladder cancer.

Fluoxetine regulates cell growth inhibition of interferon-α

“…For instance, the synergic cell growth inhibition and apoptosis of IFN-α are observed in human T-cell lymphotropic virus type I-transformed cells combined with arsenic trioxide (8), in transformed T-and monocytoid cell lines combined with IL-21 (9), in HCC combined with 5-fluorouracil (10), or in bladder cancer cells combined with proanthocyanidin (11). These results indicate that a combinatorial strategy is more effective to antitumor action.…”

Recent Advances in Anticancer Activities and Drug Delivery Systems of Tannins

“…Interestingly, PAs were also applied as chemosensitive candidates to combine with chemotherapeutic agents for synergistic anticancer efficacy, such as interferon, doxorubicin, cisplatin, and so on . In a previous study, the combination of interferon‐α2b (50K IU/mL) and GSP (25 μg/mL) showed a drastic growth reduction up to 95% via induction of cell cycle arrest in G1 . With the isolation of PAs from Urceola huaitingii , nine novel compounds were identified and the anticancer efficacies of them were also investigated, which showed that PAs with high degrees of polymerization might have higher antiproliferative effect and PAs with two doubly interflavonoid linkages possessed stronger synergistic anticancer efficacy with chemotherapeutic agents (doxorubicin or cispaltin) compared to those with single doubly interflavonoid linkage .…”

“…Interestingly, PAs were also applied as chemosensitive candidates to combine with chemotherapeutic agents for synergistic anticancer efficacy, such as interferon, doxorubicin, cisplatin, and so on . In a previous study, the combination of interferon‐α2b (50K IU/mL) and GSP (25 μg/mL) showed a drastic growth reduction up to 95% via induction of cell cycle arrest in G1 .…”

Anticancer Activities of Hesperidin and Hesperetin In vivo and their Potentiality against Bladder Cancer

“…One of the strategies would be to investigate hesperidin or hesperetin as coadjuvant of the chemotherapeutics regiment in bladder cancer (e.g., DOX, CIS, MMC, etc.). Perspectives of this research might be great, if we joint our expertise in bladder cancer on animals [57][58][59][60][61][62][63][64][65][66][67][68][69][70][71] and easiness of obtaining hesperidin and hesperetin in our laboratories. At last bit not at least, this mini-review shows the importance of introducing new, nontoxic and economically feasible natural products for the cancer treatment.…”