Knockdown of Ki-67 by Dicer-Substrate Small Interfering RNA Sensitizes Bladder Cancer Cells to Curcumin-Induced Tumor Inhibition

Abstract

Transitional cell carcinoma (TCC) of the urinary bladder is the most common cancer of the urinary tract. Most of the TCC cases are of the superficial type and are treated with transurethral resection (TUR). However, the recurrence rate is high and the current treatments have the drawback of inducing strong systemic toxicity or cause painful cystitis. Therefore, it would be of therapeutic value to develop novel concepts and identify novel drugs for the treatment of bladder cancer. Ki-67 is a large nucleolar phosphoprotein whose expression is tightly linked to cell proliferation, and curcumin, a phytochemical derived from the rhizome Curcuma longa, has been shown to possess powerful anticancer properties. In this study, we evaluated the combined efficacy of curcumin and a siRNA against Ki-67 mRNA (Ki-67-7) in rat (AY-27) and human (T-24) bladder cancer cells. The anticancer effects were assessed by the determination of cell viability, apoptosis and cell cycle analysis. Ki-67-7 (10 nM) and curcumin (10 µM), when treated independently, were moderately effective. However, in their combined presence, proliferation of bladder cancer cells was profoundly (>85%) inhibited; the rate of apoptosis in the combined presence of curcumin and Ki-67-7 (36%) was greater than that due to Ki-67-7 (14%) or curcumin (13%) alone. A similar synergy between curcumin and Ki-67-7 in inducing cell cycle arrest was also observed. Western blot analysis suggested that pretreatment with Ki-67-7 sensitized bladder cancer cells to curcumin-mediated apoptosis and cell cycle arrest by p53- and p21-independent mechanisms. These data suggest that a combination of anti-Ki-67 siRNA and curcumin could be a viable treatment against the proliferation of bladder cancer cells.

Polyphenolic Compounds Targeting p53-Family Tumor Suppressors: Current Progress and Challenges

“…)=acetylated lysine, p(ser. )=phosphorylated serine -increased expression of p53 and p73 [83,198] Ovarian -no change or increased expression of p53 [202,203] Erhlich Ascite carcinoma cells -increased expression of p53-ac(lys373) and total p53 [120] Colorectal cancer cells (LoVo, HCT116, p53-null HCT116, p53mutated HT29, p53-mutated Colo205)…”

New insight into ectopic thyroid glands between the neck and maxillofacial region from a 42-case study

“…Ki-67 is a large nucleolar phosphoprotein that participates the regulation of cell cycle and cell proliferation. Detailed cell cycle analysis revealed that Ki-67 antigen is present in the nuclei of actively proliferating cells (G1, S and G2 phase and mitosis) but not in the nuclei of quiescent or resting cells (G0 phase) [ 10 ]. The fraction of Ki-67-positive tumor cells (the Ki-67 labeling index) is often correlated with the clinical course of cancer patients [ 11 ].…”

Licochalcone A-Induced Human Bladder Cancer T24 Cells Apoptosis Triggered by Mitochondria Dysfunction and Endoplasmic Reticulum Stress

“…Most of the TCC cases are of the superficial type and are treated with transurethral resection (TUR). However, the recurrence rate is high and the current treatments have the drawback of inducing strong systemic toxicity or causing painful cystitis [4]. Therefore, efforts to develop a novel treatment to combat the disease with less side effects must necessarily be increased.…”