Capsaicin enhances anti-proliferation efficacy of pirarubicin via activating TRPV1 and inhibiting PCNA nuclear translocation in 5637 cells

Abstract

The recurrence of bladder cancer after surgery with or without chemotherapy remains a major challenge in bladder cancer treatment. Previous studies have shown that transient receptor potential vanilloid 1 (TRPV1) acts as a tumor suppressor through inducing apoptosis in bladder cancer cells. However, whether activation of TRPV1 has any synergistic effects with pirarubicin (THP), one of main drugs used in urinary bladder instillation chemotherapy to improve chemotherapeutic efficacy has remained elusive. The present study verified that TRPV1 was differentially expressed in bladder cancer cell lines. Furthermore, activation of TRPV1 by capsaicin was shown to induce growth inhibition of 5637 cells in which TRPV1 was highly expressed, while the growth of T24 cells, which express TRPV1 at low levels, was not affected. In addition, the present study demonstrated that activation of TRPV1 enhanced the anti‑proliferative effects of pirarubicin using an MTT assay and cell cycle analysis. Finally, immunofluorescent microscopy revealed that activation of TRPV1 prevented the translocation of proliferating cell nuclear antigen to the nucleus. This phenomenon was reversed by pre‑treatment with capsazepine, a specific TRPV1 antagonist. In conclusion, the present study confirmed the anti‑tumor activity of TRPV1 against bladder cancer. Activation of TRPV1 may be applied as a novel strategy to treat bladder cancer or enhance the therapeutic efficacy of traditional chemotherapeutic drugs.

Expression and functionality of TRPV1 in breast cancer cells

“…This finding was in accordance with the results of Vercelli et al,43 who demonstrated a significant decrease in the cell growth rate of MCF-7 breast cancer cells upon capsaicin stimulation. Interestingly, Zheng et al44 furthermore showed that capsaicin was capable of enhancing the antineoplastic effects of pirarubicin, which is an analog of the antibiotic doxorubicin 45. In HCT116 cells, the inhibition of cell proliferation by TRPV1 signaling was demonstrated as well.…”

Capsaicin synergizes with camptothecin to induce increased apoptosis in human small cell lung cancers via the calpain pathway

“…Similarly, the treatment of stomach cancer cells with a combination of cisplatin and capsaicin caused greater than apoptosis than either of these agents given singly [11, 12]. A similar effect was also observed when capsaicin was given in combination with the doxorubicin analog pirarubicin [13]. The present manuscript investigates for the first time the anti-cancer activity of the combination of capsaicin and camptothecin.…”

Applicability of electrospun polypropylene carbonate polymers as a drug carrier for sirolimus

“…Subsequent to the first investigations into polymer-controlled drug release in cancer therapy (8,24,25), the field has rapidly expanded and applied to the treatment of other diseases (18,26,27). Aliphatic polyesters, particularly PLGA, have been extensively explored for local drug delivery.…”

“…Preparation of PPC polymer loaded with sirolimus. Various ratios of PPC and sirolimus were used to produce PPC-sirolimus polymers and cell growth experiments, performed by MTT assay as previously described (18), demonstrated that the polymer made with 900 mg PPC and 100 mg sirolimus resulted in the greatest cell inhibitory effect; therefore, this ratio was used in the present study. The polymer solution was as follows: 1,000 mg PPC alone (PPC polymer) or 900 mg PPC plus 100 mg sirolimus (PPC-sirolimus polymer) was dissolved in 10 ml acetonitrile following stirring for 6 h. Electrospinning was performed using the electrospinning apparatus (Model ET2535; Beijing Ucalery Technology and Development Co., Ltd., Beijing, China).…”