Promising anticancer activity of cromolyn in colon cancer: in vitro and in vivo analysis.

PURPOSE: Colon cancer is a prevalent cancer globally, representing approximately 10% of all cancer cases and accounting for 10% of all cancer-related deaths. Therefore, finding new therapeutic methods with high efficiency will be very valuable. Cromolyn (C), a common anti-allergic and mast cell membrane stabilizing drug, has recently shown valuable anti-cancer effects in several studies. This study was designed to investigate the anti-cancer activity of cromolyn on colon cancer in vitro and in vivo and to determine values such as selectivity index and survival effect. METHODS: HT-29 (colon cancer) and MCF-10 (normal epithelial) cell lines were treated with C and Doxorubicin (DOX; Positive control). IC50 values and the effects of C and DOX on apoptosis were explored using methyl thiazole diphenyl-tetrazolium bromide (MTT) assay and Annexin V/PI Apoptosis Assay Kit. To investigate in an animal study, colon cancer was subcutaneously induced by CT26 cells (mouse colon cancer) in bulb/c mice. Mice were treated with 0.05 LD50 intraperitoneal every other day for 35 days. After the death of mice, tumor volume, tumor weight, and survival rate were evaluated. RESULTS: C selectively and significantly suppressed the proliferation of cancer cells in a dose-dependent manner. The IC50 values for the MCF-10 and HT29 cell lines were 7.33 ± 0.78 µM and 2.33 ± 0.6 µM, respectively. Notably, the selective index (SI) highlighted that C displayed greater selectivity in inhibiting cancer cell growth compared to DOX, with SI values of 3.15 and 2.60, respectively. C exhibited higher effectiveness and selectivity in inducing apoptosis in cancer cells compared to DOX, with a significant p-value (61% vs. 52%, P-value ≤ 0.0001). Also, in mice bearing colon cancer, C reduced the tumor volume (6317 ± 1685mm3) and tumor weight (9.8 ± 1.6 g) compared to the negative control group (weight 12.45 ± 0.9 g; volume 7346 ± 1077) but these values were not statistically significant (P ≤ 0.05). CONCLUSION: Our study showed that cromolyn is a selective and strong drug in inhibiting the proliferation of colon cancer cells. Based on our results, the efficacy of C in vitro analysis (MTT assays and apoptosis), as well as animal studies is competitive with the FDA-approved drug doxorubicin. C is very promising as a low-complication and good-efficacy drug for cancer drug repositioning. This requires clinical research study designs to comprehensively evaluate its anti-cancer effects.

In vitro and in vivo anticancer activity of mebendazole in colon cancer: a promising drug repositioning.

Colon cancer is one of the most common cancers and one of the main causes of death worldwide. Therefore, new treatment methods with better efficiency and fewer risks are very necessary. Mebendazole (MBZ), a drug commonly used for helminthic infections, has recently received attention as a suitable candidate for the treatment of various cancers. This study aimed to investigate, in vitro and in vivo, anticancer activity and selectivity Index of MBZ on colon cancer. HT-29 (human colorectal adenocarcinoma) and MCF-10 (non-tumorigenic epithelial) cell lines were treated with MBZ and Doxorubicin (DOX; positive control drug). IC50 values were estimated using methyl thiazole diphenyl-tetrazolium bromide (MTT) assay. We employed flow cytometry using annexin V-FITC and propidium iodide dyes. For the animal study, colon cancer was subcutaneously induced by CT26 cells (mouse colon cancer) in Bulb/C mice. The mice were treated with 0.05 of LD50, intraperitoneal, every other day for 35 days. Finally, the survival rate, tumor volume, and tumor weight were calculated. Our results demonstrated that IC50 values after 72 h for HT29 and MCF-10 cell lines were 0.29 ± 0.04 µM and 0.80 ± 0.02 µM, respectively. MBZ was more selective than DOX in inhibiting the proliferation of cancer cells compared to normal cells (2. 75 vs. 2.45). Annexin V/PI staining demonstrated that MBZ treatment at IC50 concentrations induced (78 ± 12%) apoptosis in the HT29 cancer cell line after 48 h (P ≤ 0.0001). Also, in mice bearing colon cancer, MBZ significantly reduced the tumor volume (1177 ± 1109 mm3; P ≤ 0.001) and tumor weight (2.30 ± 1.97 g; P ≤ 0.0001) compared to the negative control group (weight 12.45 ± 2.0 g; volume 7346 ± 1077). Also, MBZ increases mean survival time (MST) and increase life span (ILS) percentage in the animal study (51.2 ± 37% vs 93%, respectively). This study suggests that mebendazole strongly and selectively inhibits proliferation and induces apoptosis in colon cancer cells. It may be, accordingly, a promising drug for clinical research and application.

MiR-211 plays a dual role in cancer development: From tumor suppressor to tumor enhancer.

Cancer is a general term for more than 100 unique malignancies in different organs of the body. Each cancer type and subtype has its own unique genetic, epigenetic, and cellular factors accountable for malignant progression and metastasis. Small non-coding RNAs called miRNAs target mRNAs and play a vital part in the pathogenesis of human diseases, specifically cancer. Recent investigations provided knowledge of the deregulation of miR-211 in various cancer types and disclosed that miR-211 has an oncogenic or tumor-suppressive impact on tumourigenesis and cancer development. Moreover, recent discoveries which clarify the essential functions of miR-211 might provide proof for its prognosis, diagnostic and therapeutic impact on cancer. Thereby, this review will discuss recent findings regarding miR-211 expression level, target genes, and mechanisms in different cancers. In addition, the most recent results that propose miR-211 usefulness as a noninvasive biomarker and therapeutic factor for the diagnosis and treatment of cancer will be explained.

Dual drug delivery system based on layered double hydroxides/carboxymethyl cellulose-poly ethylene oxide bionanocomposite electrospun fibrous mats: Fabrication, characterization, in-vitro and in-vivo studies.

The main goal of the present project was to design and develop ibuprofen (IBU) and layered double hydroxides-vancomycin (LDH-VAN) nanohybrid loaded bionanocomposite fibrous mats to increase the wound healing rate. Thus, first, LDH-VAN nanohybrid particles was synthesized by in-situ incorporation of VAN into the Mg-Al-LDH interlayers during the co-precipitation of hydroxides. Then, LDH-VAN/IBU/CMC-PEO bionanocomposite fibrous mats were fabricated by electrospinning technique. Test samples were examined XRD, SEM, TEM, TGA, and FTIR. In vitro drug release test was performed in the phosphate buffer solution (pH = 7.4) to prove the efficiency of the fabricated bionanocomposite fibrous mats as a sustained-release carrier for both VAN and IBU. All the fabricated bionanocomposite fibrous mats did not displayed any significant cytotoxicity on NIH/3 T3 fibroblast cells. The wound area in the rats treated with LDH-VAN/IBU/CMC-PEO bionanocomposite fibrous mats was less than other treatment groups. Based on histological analysis, the LDH-VAN/IBU/CMC-PEO bionanocomposite fibrous mats possess a faster wound healing than other nanofibrous mats. Data obtained from the present project indicated that LDH-VAN/IBU/CMC-PEO bionanocomposite fibrous mats could accelerate the wound healing process.