Dietary phytochemicals in colorectal cancer prevention and treatment: A focus on the molecular mechanisms involved.

Cancer is a life-threatening disease and is the second leading cause of death around the world. The increasing threats of drug-resistant cancers indicate that there is an urgent need for the improvement or development of more effective anticancer agents. Curcumin, a phenolic compound originally derived from turmeric plant (Curcuma longa L. (Zingiberaceae family)) widely known as a spice and a coloring agent for food have been reported to possess notable anticancer activity by inhibiting the proliferation and metastasis, and enhancing cell cycle arrest or apoptosis in various cancer cells. In spite of all these benefits, the therapeutic application of curcumin in clinical medicine and its bioavailability are still limited due to its poor absorption and rapid metabolism. Structural modification of curcumin through the synthesis of curcumin-based derivatives is a potential approach to overcome the above limitations. Curcumin derivatives can overcome the disadvantages of curcumin while enhancing the overall efficacy and hindering drug resistance. This article reports a review of published curcumin derivatives and their enhanced anticancer activities.

https://www.mdpi.com/1420-3049/24/23/4386/pdf

Curcumin and Its Derivatives as Potential Therapeutic Agents in Prostate, Colon and Breast Cancers

Synergistic effects of curcumin and its analogs with other bioactive compounds: A comprehensive review

Lead bioactive compounds of Aloe vera as potential anticancer agent

https://jebmh.com/assets/data_pdf/Ashok_-2_-_FINAL.pdf

Incidence, consequences, and risk factors for anastomotic dehiscence after colorectal surgery: a prospective monocentric study

Dimethoxycurcumin (DMC) is a lipophilic analog of curcumin, an effective treatment for colon cancer, which has greater chemical and metabolic stability. Chemotherapy treatments, such as 5-fluorouracil (5-Fu), play a key role in the current management of colon cancer. In this study, we investigated the antitumor efficacy of DMC in combination with 5-Fu in SW480 and SW620 colon cancer cells. CCK-8 assay was used to evaluate the inhibitory effect of DMC and 5-Fu on cancer cells proliferation, and the combination index was calculated. The influence of DMC and 5-Fu on cell cycle, apoptosis, reactive oxygen species (ROS) production, and mitochondrial membrane potential in SW480 and SW620 cells was determined using flow cytometry, and the related signaling pathways were detected by western blot. Transmission electron microscopy was used to observe endoplasmic reticulum expansion. DMC- and/or 5-Fu-induced apoptosis, stimulated G0/G1 phase arrest, increased ROS levels, decreased mitochondrial membrane potential, and enhanced endoplasmic reticulum expansion. The induction of apoptosis is involved in the increasing of Bax and cytochrome c and decreasing of Bcl2 expressions. Increased production of ROS was accompanied by upregulation of CHOP and Noxa. Combination therapy of DMC and 5-Fu had increased efficacy on the above pathways compared with either drug alone. Based on the calculated IC50 , combination treatment with DMC and 5-Fu had an additive antitumor effect in both cell lines. Combined treatment with DMC and 5-Fu led to an additive antitumor effect in colon cancer cells that was related to apoptosis induction, G0/G1 phase arrest, increased ROS production, decreased mitochondrial membrane potential, and enhanced endoplasmic reticulum expansion.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/cam4.1114

In vitro additive antitumor effects of dimethoxycurcumin and 5‐fluorouracil in colon cancer cells

Background: Metastasis is the primary cause of death in colorectal cancer (CRC); the underlying mechanisms remain partly unknown. In this study, we aim to investigate the value of HOXA11-AS in survival evaluation and the potential role of HOXA11-AS/miR-149-3p axis in the CRC metastasis. Methods: The expressions of HOXA11-AS, both in obtained CRC samples and adjacent noncancerous tissues, were analyzed in survival evaluation. Competing endogenous RNAs (CeRNAs) Analysis were employed to reveal the potential relationship between HOXA11-AS and miR-149-3p. It was further confirmed by Quantitative real-time polymerase chain reaction (qRT-PCR) and Dual-luciferase reporter assay. Migration and invasion assay were used to verify the potential role of HOXA11-AS and miR-149-3p in the regulation of CRC metastasis. The potential pathway was explored by Western blot analysis. Results: The expression of HOXA11-AS in the CRC tissue is significantly higher than the expression in adjacent noncancerous tissue (p<0.0001). High expressions of HOXA11-AS were noticeably correlated with clinicopathologic characteristics including advanced clinical stage (p=0.021), larger tumor size (p<0.001) and frequent tumor recurrence (p=0.001). The overall survival in HOXA11-AS-High group was significantly shorter than the HOXA11-AS-Low group (p<0.001). Advanced clinical stage, tumor size and high expression of HOXA11-AS were showed as independent prognostic prediction factors for the 5-year tumor relapse of CRC patients (p<0.001). HOXA11-AS acts as a potential molecular sponge for miR-149-3p, in the promotion of CRC metastasis. In the miR-149-3p mimic-treated group, the expression of E-cadherin was increased, whereas the expression of N-cadherin, Snail, Slug, TGF-β1, Wnt2b, Twist and C/EBPβ was decreased. Conclusion: This study demonstrates that high expression of HOXA11-AS is correlated with CRC progression and poor prognosis and may promote metastasis via EMT by modulating miR-149-3p.

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The long non-coding RNA HOXA11-AS promotes epithelial mesenchymal transition by sponging miR-149-3p in Colorectal Cancer.

Synchronous isolated splenic metastasis from cancer of hepatic flexure of colon: A case report.

An anastomotic leak (AL) is the most serious complication observed in laparoscopic anterior resection of rectal cancer (LARRC). In order to protect anastomosis from AL and avoid stoma reversal surgery in patients with ileostomy, spontaneously closing cannula ileostomy (SCCI) was used in LARRC and its safety and feasibility were assessed in the present study. To the best of our knowledge, this is the first time that SCCI has been used in such a case. A total of 41 patients who underwent LARRC with SCCI or ileostomy procedures between November 2013 and August 2014 were retrospectively analyzed. The patient demographics, clinical features and surgical data were evaluated using a Mann-Whitney U-test, Fisher's exact test or linear-by-linear association. Demographics, surgical data and the majority of clinical features of the two groups were consistently similar. In the SCCI group, the length of postoperative stay, total cost and stoma period were significantly improved compared with those in the ileostomy group. Additionally, the median protective period in the SCCI group was 22 days [interquartile range (IQR), 19-22 days], the median time to cannula removal was 23 days (IQR, 20-24 days) and the median time to cannula stoma closure was 12 days (IQR, 11-13 days). No SCCI-associated complications occurred. No significant differences in routine complications, including staple-line bleeding, anastomotic leak, anastomotic dehiscence, anastomotic stenosis and wound infection, were identified between the two groups. In LARRC, the SCCI procedure was demonstrated to be a safe and feasible diverting technique to protect anastomosis from AL. In contrast to ileostomy, the SCCI procedure obviated the requirement for stoma reversal surgery, which resulted in decreased lengths of postoperative hospital stay, hospitalization costs and stoma periods.

/pdf/application-of-spontaneously-closing-cannula-ileostomy-in-3dv09ywy3u.pdf

Huiying Zhao

Papers

In vitro additive antitumor effects of dimethoxycurcumin and 5‐fluorouracil in colon cancer cells

The long non-coding RNA HOXA11-AS promotes epithelial mesenchymal transition by sponging miR-149-3p in Colorectal Cancer.

Synchronous isolated splenic metastasis from cancer of hepatic flexure of colon: A case report.

Application of spontaneously closing cannula ileostomy in laparoscopic anterior resection of rectal cancer