Curcumin inhibits malignant behavior of colorectal cancer cells by regulating M2 polarization of tumor-associated macrophages and metastasis associated in colon cancer 1 (MACC1) expression.

The present study was to investigate the underlying mechanism of the antitumor effect of curcumin in colorectal cancer cells, focusing on the M2 polarization of tumor-associated macrophages (TAMs). The effect of curcumin on the malignant behavior of colorectal cancer cells was investigated by WST assay for cell growth, and Transwell assay for cell migration/invasion. THP-1 cells were differentiated into macrophages and coculture with colorectal cancer cells to study the influence of curcumin on M2 polarization, presenting as the levels of ARG1 mRNA, IL-10, and CD163-positive cells. GEO database was searched for the shared altered gene of curcumin in colorectal cells and human monocytes. Molecular docking was used to visualize the binding between curcumin and MACC1. Curcumin restricted the proliferation, apoptosis, and migration/invasion of HCT 116 and SW620 cells. Curcumin attenuated levels of the M2 macrophage markers, CD163 + cells, IL-10 secretion, and ARG1 mRNA. MACC1 was a target of curcumin in colorectal cancer cells, relating to macrophage. Rescue experiments showed that MACC1 overexpression can reverse the antitumor effect of curcumin in colorectal cancer cells and M2 polarization of TAMs. Curcumin's antiproliferative and anti-migratory effects in colorectal cancer cells may be mediated by MACC1 and inhibition of M2 polarization of TAMs.

Folate-functionalized SMMC-7721 liver cancer cell membrane-cloaked paclitaxel nanocrystals for targeted chemotherapy of hepatoma.

In this study, we prepared a folic acid-functionalized SMMC-7721 liver cancer cell membrane (CM)-encapsulated paclitaxel nanocrystals system (FCPN) for hepatoma treatment. Transmission electron microscopy (TEM) characterization showed that FCPN was irregular spherical shapes with a particle size larger than 200 nm and a coated thickness of approximately 20 nm. In an in vitro release experiment, FCPN indicated a slowly release effect of paclitaxel (PTX). Cell experiments demonstrated that FCPN was taken up by SMMC-7721 cells and significantly inhibited the proliferation of SMMC-7721 cells, which illustrated that FCPN had good targeting ability compared with PN and CPN. According to the results of in vivo animal experiments, FCPN significantly inhibited tumor growth. Tissue distribution experiments proved that FCPN could accumulate significantly in tumor tissues, which further explained why FCPN had good targeting ability. These results clearly suggested that folate-functionalized homotypic CM bionic nanosystems might represent a very valuable method for liver cancer treatment in the future.

Puerarin Alleviates UUO-Induced Inflammation and Fibrosis by Regulating the NF-κB P65/STAT3 and TGFß1/Smads Signaling Pathways.

PURPOSE: Puerarin (PR), a Chinese medicine rich in natural components, has been reported to display anti-fibrotic, antioxidant, anti-inflammatory and immunomodulatory properties. However, the protective mechanism of PR against unilateral ureteral obstruction (UUO)-mediated renal injury is not fully clarified. Therefore, the aim of this study was to investigate the effects of PR on UUO mice and its possible mechanisms. METHODS: A total of 32 C57BL/6 mice were divided randomly into four groups (n=8): i) sham-operated group (Sham); ii) UUO group (UUO); iii) UUO + PR 50 mg/kg/day (UUO + PRL); and iv) UUO + PR 100 mg/kg/day (UUO + PRH). Continuous gavage administration for 14 days starting one week postoperatively, while the mice in Sham and UUO groups were given equal amounts of vehicle by the same means. All mice were then sacrificed and serum, 24-hour urine and tissue specimens were collected for renal function, histopathology, Western blot, immunohistochemistry. RESULTS: Renal function and histopathology revealed that PR improved UUO-mediated renal dysfunction and partially reversed tubular injury and tubulointerstitial fibrosis. Additionally, according to the results of Western blot and immunohistochemistry, PR inhibited the expression of inflammatory factors including IL-1ß, IL-6, MCP-1 and ECM-related proteins including α-SMA, COL I and VIM. More importantly, the expression of fibrotic pathways TGF-ß1, Smad3, p-Smad3 and inflammatory pathways NF-κB p65, NF-κB p-p65, STAT3, p-STAT3 were inhibited to various extents under the PR treatment, while Smad7 was upregulated. CONCLUSION: These findings indicate that PR may inhibit the recruitment of inflammatory factors and extracellular matrix (ECM) deposition through the regulation of the NF-κB p65/STAT3 and TGFß1/Smads pathways, which alleviates the UUO-induced inflammatory and fibrotic response, thereby reversing renal injury.

Evodiamine exerts anticancer effects via induction of apoptosis and autophagy and suppresses the migration and invasion of human colon cancer cells.

PURPOSE: Colon cancer ranks as the fourth common type of cancer and is responsible for significant morbidity and mortality throughout the world. Late diagnosis and the rarity of potent and safer chemotherapeutic drugs and efficient therapeutic targets create severe obstacle in the treatment of colon cancer. This study was undertaken to examine the anticancer effects of Evodiamine against human colon cancer cells. METHODS: The proliferation rate of the SW480 colon cancer cells was monitored by MTT assay. Apoptosis was detected by Annexin V/propidium iodide (PI) and acridine orange (AO)/ethidium bromide (EB) staining. Transmission electron microscopy (TEM) was used for detection of autophagy. Cell migration and invasion was detected by wound healing and transwell assays, respectively. Protein expression was determined by western blotting. RESULTS: Evodiamine suppressed the proliferation of the SW480 colon cancer cells and exhibited an IC50 of 10 µM. The cytotoxic effects of Evodiamine were found to be comparatively lower against the normal CDD-18Co colon cells as evidenced from the IC50 of 100 µM. AO/EB staining showed that Evodiamine caused apoptosis of the SW480 cells and the percentage of the apoptotic SW480 cells increased with increase in the Evodiamine concentration as indicated by annexin V/PI staining. Evodiamine-induced apoptosis was also accompanied by upregulation of caspase-3 and Bax and suppression of Bcl-2. TEM analysis showed that Evodiamine also activated autophagy in the SW480 cells by enhancing the expression of LC3 II and Beclin 1. The wound assay showed that Evodiamine suppressed the migration of the SW480 cells. Evodiamine also reduced the invasion potential of the SW480 cells as suggested by the transwell assay. CONCLUSION: The findings of the present study suggest that Evodiamine is a potent anticancer agent and may prove beneficial in the development of systemic therapy of colon cancer.

Identification of long non­coding RNA­mediated transcriptional dysregulation triplets reveals global patterns and prognostic biomarkers for ER+/PR+, HER2­ and triple negative breast cancer.

Breast cancer (BRCA) is the most common type of cancer in adult females. Estrogen receptor (ER)+/progesterone receptor (PR)+, human epidermal­growth factor receptor 2 (HER2)­ BRCA and triple­negative breast cancer (TNBC) are two important subtypes of this disease. Long non­coding RNA (lncRNA)­mediated transcriptional dysregulation triplets (lncTDTs) may contribute to the development of cancer; however, the precise functional roles of lncTDTs in ER+/PR+, HER2­ BRCA and TNBC require further investigation. In the present study, an integrated and computational approach was conducted to identify lncTDTs based on transcription factor (TF), gene, lncRNA expression profiles and experimentally verified TF­gene interactions. The regulatory patterns of these lncTDTs are complex and differed in ER+/PR+, HER2­ BRCA and TNBC. Of note, five common lncTDTs were reported for these BRCA subtypes. Functional analysis revealed lncTDTs to be enriched in the PI3K/AKT signaling pathway within the two BRCA subtypes. Additionally, certain lncTDTs were associated with survival and may be considered candidate prognostic biomarkers for BRCA subtypes. Collectively, the results of the present study provide novel insight into the functions and mechanisms of lncRNAs in ER+/PR+, HER2­ BRCA and TNBC, and may aid the development of targeted treatments against certain subtypes of BRCA.

RETRACTED: Ailanthone exerts anticancer effect by up-regulating miR-148a expression in MDA-MB-231 breast cancer cells and inhibiting proliferation, migration and invasion.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief. Given the comments of Dr Elisabeth Bik regarding this article "… the Western blot bands in all 400+ papers are all very regularly spaced and have a smooth appearance in the shape of a dumbbell or tadpole, without any of the usual smudges or stains. All bands are placed on similar looking backgrounds, suggesting they were copy/pasted from other sources, or computer generated", the journal requested the authors to provide the raw data. However, the authors were not able to fulfil this request and therefore the Editor-in-Chief decided to retract the article.

Boswellic acid exerts potent anticancer effects in HCT-116 human colon cancer cells mediated via induction of apoptosis, cell cycle arrest, cell migration inhibition and inhibition of PI3K/AKT signalling pathway.

PURPOSE: Boswellic acid is an important plant-derived natural product with tremendous pharmacological potential and has been reported to inhibit the growth of several types of cancer cells. In this study we report the anticancer activity of boswellic acid against human colon cancer cells via induction of apoptosis, cell cycle arrest and inhibition of cell migration and PI3K/AKT signalling pathway. METHODS: The antiproliferative effects of boswellic acid were assessed by MTT assay using different doses of the drug. The apoptotic effects were studied by DAPI and annexin V/PI staining assays, and cell cycle distribution was studied by flow cytometry. The effects of the drug on PI3K/AKT protein expression were studied using western blot analysis. RESULTS: The results of this study showed that boswellic acid suppresses the growth of HCT-116 colon cancer cells. The anticancer effects were found to be dose-dependent and the IC50 value was 15 µM against the HCT-116 colon cancer cells. The inhibition of growth of these cancer cells was mainly due to apoptosis and G2/M cell cycle arrest. Besides, boswellic acid altered the Bax/Bcl-2 ratio in the HCT-116 cancer cells and inhibited their migration as indicated by the cell migration assay. It was observed that boswellic acid decreased the expression of p-PI3K and p-AKT in a concentration- dependent manner. However, the expression of PI3K and AKT remained almost unaltered. CONCLUSION: In conclusion, these results clearly suggest that boswellic acid could be employed in the treatment of colon cancer provided further in vivo and other in depth experiments are done.

Function of miR-152 as a Tumor Suppressor in Human Breast Cancer by Targeting PIK3CA.

miR-152, as a tumor suppressor, has been reported to be downregulated in a number of cancer cell lines and tumor tissues, including breast cancer. This study aimed to investigate the role of miR-152 in human breast cancer and its underlying mechanisms. Human breast cancer cell line HCC1806 was transfected with hsa-miR-152-3p mimic, inhibitor, or scrambled negative controls. The efficiency of miR-152-3p transfection was evaluated by quantitative real-time PCR, and the effects on cell viability and apoptosis as well as on the PI3K/AKT signaling pathway were investigated by MTT assay, flow cytometry, and Western blot analysis, respectively. The binding effect of miR-152-3p on PIK3CA 3'-UTR was also investigated. The results suggested that miR-152-3p mimic transfection inhibited cell viability while inducing apoptosis of HCC1806 cells. Furthermore, miR-152-3p negatively regulated PIK3CA expression via binding to the 3'-UTR of PIK3CA and decreased the phosphorylation levels of AKT (Ser473) and RPS6 (Ser235/236) in HCC1806 cells. miR-152-3p inhibitor transfection showed the opposite effects. In conclusion, miR-152-3p might serve as a tumor suppressor in human breast cancer cells via negatively regulating PIK3CA expression to inhibit the activation of AKT and RPS6, leading to suppression of HCC1806 cell proliferation.