Resistance to 3‐HTMC‐Induced Apoptosis Through Activation of PI3K/Akt, MEK/ERK, and p38/COX‐2/PGE₂ Pathways in Human HT‐29 and HCT116 Colorectal Cancer Cells

Abstract

Increasing incidence and mortality of colorectal cancer brings the necessity to uncover new possibilities in its prevention and treatment. Chalcones have been identified as interesting compounds having chemopreventive and antitumor properties. In this study, we investigated the effects of the synthetic chalcone derivative 3-hydroxy-3',4,4',5'-tetra-methoxy-chalcone (3-HTMC) on proliferation, cell cycle distribution, apoptosis, and its mechanism of action in human colorectal HT-29 (COX-2 sufficient) and HCT116 (COX-2 deficient) cancer cells. We showed that 3-HTMC decreased cell viability in a dose-dependent manner with a more potent antiproliferative effect on HCT116 than HT-29 cells. Flow cytometric analysis revealed G /M cell cycle accumulation in HT-29 cells and significant G /M arrest in HCT116 cells with a subsequent apoptosis shown by appearance of Sub-G1 peak. We demonstrated that 3-HTMC treatment on both cell lines induced apoptotic process associated with overexpression of death receptor DR5, activation of caspase-8 and -3, PARP cleavage, and DNA fragmentation. In addition, 3-HTMC induced activation of PI3K/Akt and MEK/ERK principal survival pathways which delay 3-HTMC-induced apoptosis in both cell lines. Furthermore, COX-2 overexpression in HT-29 cells contributes to apoptosis resistance which explains the difference of sensitivity between HT-29 and HCT116 cells to 3-HTMC treatment. Even if resistance mechanisms to apoptosis reduced chalcone antitumoral potential, our results suggest that 3-HTMC may be considered as an interesting compound for colorectal cancer therapy or chemoprevention. J. Cell. Biochem. 117: 2875-2885, 2016. © 2016 Wiley Periodicals, Inc.

Antiproliferation for Breast Cancer Cells by Ethyl Acetate Extract of Nepenthes thorellii x (ventricosa x maxima)

“…Oxidative stress is an activator for triggering apoptosis [32]. SubG1 accumulation is one of the apoptosis indicators [33]. In the current study, EANT partly induces subG1 accumulation and increases the intensity of annexin V. These apoptosis events were suppressed by NAC pretreatment, suggesting that EANT induces apoptosis of breast cancer cells depending on oxidative stress.…”

SPNS2 promotes the malignancy of colorectal cancer cells via regulating Akt and ERK pathway

“…[33][34][35] ERK is an important factor for regulating proliferation, apoptosis, migration and invasion through various signalling in CRC cells. [36][37][38][39] Our findings demonstrated that overexpression of SPNS2 increased Akt and ERK phosphorylation and SPNS2-induced malignant behaviours were abolished by Akt or ERK inhibitor, suggesting that SPNS2 may regulate the malignancy of CRC cells by activating Akt and ERK signalling.…”

Cullin7 promotes epithelial‑mesenchymal transition of esophageal carcinoma via the ERK‑SNAI2 signaling pathway

“…This corresponds with previous reports of the invasion-and metastasis-promoting roles of CUL7 in liver carcinoma (15,16), which further indicated a close association between CUL7 and EC progression. The ERK signaling pathway is also considered an important factor in various types of cell behaviors, including proliferation, migration and drug resistance (19,20), and results from the present study indicated that CUL7 may promote EMT via the ERK-SNAI2 signaling pathway, which may suggest novel targets for the treatment of EC.…”