curcumin and Rectal-Neoplasms

Colorectal cancer (CRC) is the third most common cancer in men and the second most common in women. Treatment of metastatic CRC consists of highly toxic chemotherapeutic drug combinations that often negatively affect patient quality of life (QoL). Moreover, chemotherapy-induced toxicity and chemotherapy resistance are among the most important factors limiting cancer treatment and can lead to the interruption or discontinuation of potentially effective therapy. Several preclinical studies have demonstrated that curcumin acts through multiple cellular pathways and possesses both anti-cancer properties against CRC and the capacity to mitigate chemotherapy-related side effects and overcome drug resistance. In this review article, we suggest that the addition of curcumin to the standard chemotherapeutic treatment for metastatic CRC could reduce associated side-effects and overcome chemotherapy resistance, thereby improving patient QoL.

Topics: Colonic Neoplasms; Curcumin; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Quality of Life; Rectal Neoplasms

To investigate the function of repair gene LIG4 in radiosensitivity enhancement of rectal cancer cells by curcumin.. Human rectal cancer cells HT-29 were cultured in normal. LIG4-overexpression HT-29 cells and blank control plasmid HT-29 cells were established by gene transfection. Both kind of HF-29 cells were further randomly divided into curcumin group, radiotherapy group, curcumin plus radiotherapy group (combined group) and control group. The growth inhibition and apoptosis of cells were detected by MTT and Annexin V/PI respectively. Change of tumor volume was observed in nude mouse xenograft model, and the apoptosis of tumor cells was analyzed by TUNEL.. Regarding blank control plasmid HT-29 cells, the growth inhibition rate and apoptosis rate in combined group were significantly higher than those in radiotherapy group(all P<0.05); tumor volume of nude mouse in combined group was significantly smaller than that in radiotherapy group, and the apoptotic index in combined group was significantly higher than that in radiotherapy group (all P<0.05). However, regarding LIG4-overexpression HT-29 cells, the growth inhibition rate and apoptosis rate were not significantly different between combined group and radiotherapy group(all P>0.05); the tumor volume of nude mouse and the apoptotic index were also not significantly different between combined group and radiotherapy group (all P>0.05).. Down-regulation of LIG4 is an important mechanism of radiosensitivity enhancement of rectal cancer cells by curcumin.

Topics: Animals; Apoptosis; Cell Count; Curcumin; Down-Regulation; HT29 Cells; Humans; Mice; Mice, Nude; Plasmids; Radiation Tolerance; Rectal Neoplasms; Transfection

To elucidate the mechanism of curcumin in radiotherapy sensitization for colorectal cancer cells.. Colorectal cancer HT-29 cells were cultured and treated with radiation and curcumin. MTT method was used to detect the cell growth inhibition. Then the high-throughput microarray was used to detect the differences in gene expression levels for each test group to identify differentially expressed genes, and each differential gene was validated by Western blotting.. Cell growth inhibition rates at 48-hour and 72-hour in curcumin combined with radiotherapy group were significantly higher than those in simple radiotherapy group (P<0.05). Expression of 95 genes associated with gene-injury repair was detected by microarray. Compared to simple radiotherapy group, LIG4 and PNKP expression was down-regulated, and XRCC5 and CCNH expression was up-regulated in the curcumin combined with radiotherapy group (all P<0.05). Western blotting revealed LIG4 and PNKP protein expression decreased, and XRCC5 and CCNH protein expression increased in the curcumin combined with radiotherapy group as compared to the simple radiotherapy group (all P<0.05).. Radiation sensitization effect of curcumin on colorectal cancer cells HT-29 may be associated with the regulation of genes of CCNH, LIG4, XRCC5, PNKP.

Topics: Blotting, Western; Cell Line, Tumor; Curcumin; Down-Regulation; Gene Expression; Gene Expression Regulation, Neoplastic; Humans; Rectal Neoplasms

Radiation therapy is an integral part of the preoperative treatment of rectal cancers. However, only a minority of patients achieve a complete pathologic response to therapy because of resistance of these tumors to radiation therapy. This resistance may be mediated by constitutively active pro-survival signaling pathways or by inducible/acquired mechanisms in response to radiation therapy. Simultaneous inhibition of these pathways can sensitize these tumors to radiation therapy.. Human colorectal cancer cells were exposed to clinically relevant doses of gamma rays, and the mechanism of their radioresistance was investigated. We characterized the transcription factor nuclear factor-kappaB (NF-kappaB) activation as a mechanism of inducible radioresistance in colorectal cancer and used curcumin, the active ingredient in the yellow spice turmeric, to overcome this resistance.. Curcumin inhibited the proliferation and the post-irradiation clonogenic survival of multiple colorectal cancer cell lines. Radiation stimulated NF-kappaB activity in a dose- and time-dependent manner, whereas curcumin suppressed this radiation-induced NF-kappaB activation via inhibition of radiation-induced phosphorylation and degradation of inhibitor of kappaB alpha, inhibition of inhibitor of kappaB kinase activity, and inhibition of Akt phosphorylation. Curcumin also suppressed NF-kappaB-regulated gene products (Bcl-2, Bcl-x(L), inhibitor of apoptosis protein-2, cyclooxygenase-2, and cyclin D1).. Our results suggest that transient inducible NF-kappaB activation provides a prosurvival response to radiation that may account for development of radioresistance. Curcumin blocks this signaling pathway and potentiates the antitumor effects of radiation therapy.

Topics: Apoptosis; Cell Line, Tumor; Cell Proliferation; Colonic Neoplasms; Colorectal Neoplasms; Curcumin; Dose-Response Relationship, Drug; Enzyme Inhibitors; Gene Expression Regulation; HT29 Cells; Humans; Neoplasm Proteins; NF-kappa B; Phosphorylation; Proto-Oncogene Proteins c-akt; Radiation Tolerance; Radiation-Sensitizing Agents; Rectal Neoplasms