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2017 ; 8
(ä): 593
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Colocynth Extracts Prevent Epithelial to Mesenchymal Transition and Stemness of
Breast Cancer Cells
#MMPMID28928657
Chowdhury K
; Sharma A
; Kumar S
; Gunjan GK
; Nag A
; Mandal CC
Front Pharmacol
2017[]; 8
(ä): 593
PMID28928657
show ga
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.