(-)-Kusunokinin inhibits breast cancer in N-nitrosomethylurea-induced mammary tumor rats
EUROPEAN JOURNAL OF PHARMACOLOGY
Authors: Tedasen, Aman; Dokduang, Sirinapa; Sukpondma, Yaowapa; Lailerd, Narissara; Madla, Siribhorn; Sriwiriyajan, Somchai; Rattanaburee, Thidarath; Tipmanee, Varomyalin; Graidist, Potchanapond
Abstract
Natural and synthetic (-)-kusunokinin inhibited breast cancer, colon cancer and cholangiocarcinoma cells at the G2/M phase and induced apoptosis. However, there is no report on the action and adverse effects of (-)-kusunokinin in animal models. In this study, we investigated the cytotoxic effect of (-)-kusunokinin from Piper nigrum on cancer cells. NMU-induced rat mammary tumors, an ER positive breast cancer model, were treated with (-)-kusunokinin. Proteins of interest related to cell cycle, angiogenesis, migration and signaling proteins were detected in tumor tissues. Results showed that (-)-kusunokinin exhibited strong cytotoxicity against breast, colon and lung cancer cells and caused low toxicity against normal fibroblast cells. For in vivo study, 7.0 mg/kg and 14.0 mg/kg of (-)-kusunokinin reduced tumor growth without side effects on body weight, internal organs and bone marrow. Combination of (-)-kusunokinin with a low effective dose of doxorubicin significantly inhibited tumor growth and provoked cell death in cancer tissues. Mechanistically, 14.0 mg/kg of (-)-kusunokinin decreased cell proliferation (c-Src, PI3K, Akt, p-Erk1/2 and c-Myc), cell cycle (E2f-1, cyclin B1 and CDK1), and metastasis (E-cadherin, MMP-2 and MMP-9) proteins in tumor tissues, which supports its anticancer effect. We further confirmed the antimigration effect of (-)-kusunokinin; the results show that this compound inhibited breast cancer cell (MCF-7) migration in a dose-dependent manner. In conclusion, the results suggest that 14 mg/kg of (-)-kusunokinin inhibited tumors through the reduction of signaling proteins and their downstream molecules. Therefore, (-)-kusunokinin becomes an intriguing candidate for cancer treatment as it provides a strong potency in cancer inhibition.
The use of curcumin as an effective adjuvant to cancer therapy: A short review
BIOTECHNOLOGY AND APPLIED BIOCHEMISTRY
Authors: Bashang, Hadi; Tamma, Seetha
Abstract
Turmeric (Curcuma longa) is a popular spice that has been used in Ayurvedic medicine for its ability to treat various common ailments. There have been statistical correlations between turmeric consumption and lower incidences of cancer development, prompting research into its primary component curcumin. Several in vitro and in vivo studies over the last decade into cancer treatment have provided experimental evidence that curcumin contains antiproliferative, antiangiogenic, and apoptotic properties. The results of human clinical trials however, have proven mostly to be inconclusive. This short review provides an insight into the properties of curcumin including its bioavailability, biological activity, and potential usage in clinical trials as a chemotherapeutic drug.