Colocynth Extracts Prevent Epithelial to Mesenchymal Transition and Stemness of Breast Cancer Cells

Abstract

Modern treatment strategies provide better overall survival in cancer patients, primarily by controlling tumor growth. However, off-target and systemic toxicity, tumor recurrence, and resistance to therapy are still inadvertent hurdles in current treatment regimens. Similarly, metastasis is another deadly threat to patients suffering from cancer. This has created an urgent demand to come up with new drugs having anti-metastatic potential and minimum side effects. Thus, this study was aimed at exploring the anti-proliferative and anti-metastatic potential of colocynth medicinal plant. Results from MTT assay, morphological visualization of cells and scratch assay indicated a role of ethanol and acetone extracts of fruit pulp of the colocynth plant in inhibiting cell viability, enhancing cell cytotoxicity and preventing cell migration in various cancer cell types, including breast cancer cell lines MCF-7 and MDA-MB-231, and cervical cancer cell line SiHa, subsequently having a low cytotoxic effect on mononuclear PBMC and macrophage J774A cells. Our study in metastatic MDA-MB-231 cells showed that both ethanol and acetone pulp extracts decreased transcript levels of the anti-apoptotic genes BCL2 and BCLXL, and a reverse effect was observed for the pro-apoptotic genes BAX and caspase 3. Additionally, enhanced caspase 3 activity and downregulated BCL2 protein were seen, indicating a role of these extracts in inducing apoptotic activity. Moreover, MDA-MB-231 cells treated with both these extracts demonstrated up-regulation of the epithelial gene keratin 19 and down-regulation of the mesenchymal genes, vimentin, N-cadherin, Zeb1 and Zeb2 compared to control, suggesting a suppressive impact of these extracts in epithelial to mesenchymal transition (EMT). In addition, these extracts inhibited colony and sphere formation with simultaneous reduction in the transcript level of the stemness associated genes, BMI-1 and CD44. It was also found that both the plant extracts exhibited synergistic potential with the chemotherapeutic drug doxorubicin to inhibit cancer viability. Furthermore, GC-MS/MS analysis revealed the presence of certain novel compounds in both the extracts that are responsible for the anti-cancer role of the extracts. Overall, the results of this report suggest, for the first time, that colocynth fruit pulp extracts may block the proliferative as well as metastatic activity of breast cancer cells.

Citrullus colocynthis (L.) Schrad: Chemical characterization, scavenging and cytotoxic activities

“…These findings were in agreement with the earlier data which showed an important antiproliferative effect on human breast cancer cells induced by cucurbitacin, isolated from the leaves of C. colocynthis [22]. The cytotoxic effects of the fruit pulp of C. colocynthis against cancer breast cell lines MCF-7 were studied [23]. Some chemical compounds revealed in the current extract such as ethylbenzene and tetrachloroethylene could determine the cytotoxic effect of C. colocynthis on HT-29 and MDA-MB-231 cell lines as to whether their effects are due to a single molecule or due to a potential synergy between them, and therefore further studies that may lead to determining the responsible compounds for the current activities are still appreciated.…”

GC-MS Analysis of Chemical Constituents and in vitro Antioxidant Activity of the Organic Extracts from the Stem of Bridelia stipularis

“…The major component with the highest percentage peak area was oxalic acid, cyclobutyl octadecyl ester (24.985%) at retention time 53.478 min, followed by 4-Tridecanol and nitric acid, nonyl ester with percentage peak area of 6.359% and 5.616%, respectively. Biological activity has been performed on the compound oxalic acid, cyclobutyl octadecyl ester (Chowdury et al 2017), but in the report published by Chandrakasan and Neelamegam (2011), there is no activity performed on the hydroxyl compound i.e. methyl 2-hydroxydodecanoate and the rest of the compounds.…”

Preliminary Cytotoxic Activity of Sutherlandia frutescens and Carpobrotus edulis on Malignant glioblastoma Cells

“…Our findings are consistent with previous reports for some plant extracts and other existing brain tumour therapies known to inhibit colony formation in glioblastoma cells. [42][43][44][45] Altogether, these results demonstrated that both extracts of S. frutescens and C. edulis impeded colony formation as well as survival in the U251 glioblastoma and this activity was better demonstrated in cells treated with S. frutescens.…”