Abstract
BackgroundThe development and growth of colorectal cancer based on constitutive activation of numerous signaling pathways that stimulate proliferation and metastasis. Plant-derived agents excel by targeting multiple aspects of tumor progression. Previous investigations have shown that ginger derivatives- shogaols possess anti-cancer and anti-inflammatory effects. In the present study, we have examined the anti-cancer effects of 6-shogaol alongside with the most widely used chemotherapeutic agents/regimens in the tumor-like microenvironment conditions.MethodsCytotoxicity on two colon cancer cell lines (SW480 and SW620) was measured by MTT test. Apoptosisassay, immunocytochemical and Western blotting analysis for autophagy and apoptosis detection were performed.ResultsHere, we report that 6-shogaol by itself or in combination with chemotherapeutic agents/regimens exerted a cytotoxic effect on CRC cells. Cell death might be linked with the activation of autophagy and apoptosis-related pathways. In the tumor-like microenvironment, which is characterized by hypoxia and glucose starvation, 6-shogaol with chemotherapeutics is significantly more potent than conventional chemotherapy alone.ConclusionsCollectively, our data suggest that the addition of 6-shogaol to established chemotherapeutic regimens could potentially be a remarkable therapeutic strategy for colorectal cancer.
Highlights
The development and growth of colorectal cancer based on constitutive activation of numerous signaling pathways that stimulate proliferation and metastasis
To address the above-mentioned subjects, we have investigated whether natural plant derivative- 6-shogaol enhances the anticancer effect of the most popular chemotherapeutic agents/regimens used in colon cancer treatment on two human cell lines: SW480 derived from the primary site and SW620 derived from metastatic lymph node site of the same patient
The results suggest that the treatment of 6-shogaol with chemotherapeutic agents increases the cytotoxic effect in Colorectal cancer (CRC) cells
Summary
6-shogaol is selective for cancer cells over normal healthy cells A dose-response study was performed with 6-shogaol in SW480 and SW620 adenocarcinoma cells and matched fibroblasts WI38. We found that 6-shogaol caused a significantly higher reduction of viability in both cancer cell lines as compared to the normal cells It inhibited the growth of cancer cells in a dose-dependent manner, exhibiting cytotoxicity by 95% in SW480 and 90% in SW620 at 80 μM concentration, whereas the viability of WI38 was decreased only by 17% (Fig. 1a). The results showed that 6-shogaol, FU, FOLFIRI (FU + irinotecan), FOLFOX (FU + oxaliplatin), FOLFOXIRI (FU + oxaliplatin+irinotecan) were all potent in significantly decreasing of SW480 or SW620 cell viability ranging from 30 to 65%, treatment with 6-shogaol together with chemotherapeutics caused increased cytotoxicity (98%), when compared with the control samples (statistical significance between controls was p < 0.05). In both cell lines, we observed that 6-shogaol inhibits cell viability, whereas chemotherapeutics showed no or very weak cytotoxicity in the tumor-like microenvironment. Western blot from SW480 protein lysates shows the same pattern of protein band occurrence as it was observed in immunocytochemical studies (Fig. 4)
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