Inhibition of Chemoresistance in Primary Tumor Cells by Camellia sinensis non fermentatum Extract Noviphenone (NPE®).

BACKGROUND/AIM: Despite improvements in cancer therapy, life expectancy after tumor recurrence remains low. Relapsed cancer is characterized by drug resistance, often mediated through overexpression of multidrug resistance (MDR) genes. Camellia sinensis non fermentatum extract is known for its anticancer properties in several cancer cell lines and might improve cancer therapy outcome after tumor recurrence. MATERIALS AND METHODS: Embryonal rhabdomyosarcoma cell lines, alveolar rhabdomyosarcoma cell lines and primary rhabdomyosarcoma MAST139 cells were used to test NPE® effects on cell viability in combination with chemotherapeutic agents. Cell viability was measured by the WST-1 assay and CV staining. Gene expression levels of chemotherapy-induced efflux pumps and their activity was assessed upon NPE® treatment by measuring doxorubicin retention through evaluation of the autofluorescence signal. RESULTS: Administration of increasing doxorubicin concentrations triggered immediate adaptation to the drug, which was surprisingly overcome by the addition of NPE®. Investigating the mechanism of immediate adaptation, MDR1 gene overexpression was observed upon doxorubicin treatment. Although NPE® did not alter pump gene expression, it was able to reduce pump activity, thus allowing the chemotherapeutic agent to stay inside the cells to exert its full anticancer activity. CONCLUSION: NPE® might improve chemotherapeutic treatment by re-sensitizing relapsed tumors to anticancer drugs. Fighting MDR represents the key to overcome tumor relapse and improve the overall survival of cancer patients.

Prevention of Acute Radiation-Induced Skin Reaction with NPE® Camellia Sinensis Nonfermentatum Extract in Female Breast Cancer Patients Undergoing Postoperative Radiotherapy: A Single Centre, Prospective, Open-Label Pilot Study.

BACKGROUND: To assess effectiveness of NPE, a proprietary Camellia sinensis nonfermentatum (CSNF) extract, in prevention and recovery of acute radiation-induced skin reaction (ARSR) and skin care during postoperative whole breast radiotherapy (RT). METHODS: Twenty patients were enrolled in this single centre, prospective, open-label pilot study. The outcomes of 20 prospective data sets were compared with 100 retrospectively collected matched data sets derived from hospital records. The preventive CSNF gel (2.5%) was administered 1 to 2 hours before each session on the irradiated fields. The care CSNF lotion (0.4%) was administered as 7-day pretreatment after each RT session, twice daily between RT sessions, and 4 to 8 weeks thereafter. The control group was treated according to the hospital care guidelines. The primary endpoint was time to ARSR ≥ Grade 2 (CTCAE v4.03); secondary endpoints were frequencies of ARSR grades 1, 2, 3, and 4, recovery of ARSR, frequencies of interruption and RT stop, complications and required rescue interventions, and tolerability of CSNF. RESULTS: Time to ARSR ≥ G2 (censoring) was significantly longer (p = 0.014) in the CSNF group. The hazard ratio was 2.33 (95% CI: 1.15-4.72), demonstrating a 50% decrease in the risk of developing ARSR ≥ G2. There was a trend to faster recovery from ARSR G2 in the CSNF group (100% versus 47%; p = 0.078). The proportion of patients requiring rescue treatment during RT and follow-up was markedly higher in the control compared to the CSNF group (1% to 51% versus 0% to 15%). CSNF gel and lotion were well tolerated both during and after RT. CONCLUSIONS: This pilot study provides the first evidence on the potential pharmacological effectiveness of CSNF extract in prevention of RT-induced ARSR and recovery of skin irritation in patients undergoing postoperative whole breast RT and may reflect a novel concept for prevention of RT-induced ARSR and care of irritated skin.