Multidrug Resistance Reversal and Apoptosis Induction in Human Colon Cancer Cells by Some Flavonoids Present in Citrus Plants

2012 ◽  
Vol 75 (11) ◽  
pp. 1896-1902 ◽  
Author(s):  
Olga Wesołowska ◽  
Jerzy Wiśniewski ◽  
Kamila Środa-Pomianek ◽  
Aleksandra Bielawska-Pohl ◽  
Maria Paprocka ◽  
...  
2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Chi-Tai Yeh ◽  
Chih-Jung Yao ◽  
Jiann-Long Yan ◽  
Shuang-En Chuang ◽  
Liang-Ming Lee ◽  
...  

Aberrant activation of Wnt/β-catenin signaling plays an important role in the development of colon cancer. HS7 is an active fraction extracted fromTaiwanofungus camphoratus, which had been widely used as complementary medicine for Taiwan cancer patients in the past decades. In this study, we demonstrated the effects of HS7 on the growth inhibition, apoptosis induction, and Wnt/β-catenin signaling suppression in human colon cancer cells. HS7 significantly inhibited proliferation of HT29, HCT116, and SW480 colon cancer cells in a dose- and time-dependent manner. The apoptosis induction was evidenced by DNA fragmentation and subG1 accumulation, which was associated with increased Bax/Bcl-2 ratio, activation of caspase-3 and cleavage of PARP. By using Tcf-dependent luciferase activity assay, HS7 was found to inhibit theβ-catenin/Tcf transcriptional activities. In addition, HS7 strongly suppressed the binding of Tcf complexes to its DNA-binding site shown in electrophoretic mobility shift assay. This inhibition was further confirmed by the decreased protein levels of Tcf-4 andβ-catenin. Theβ-catenin/Tcf downstream target genes, such assurvivin,c-myc,cyclin D1,MMP7, andMT1-MMPinvolved in apoptosis, invasion, and angiogenesis were also diminished as well. These results indicate thatTaiwanofungus camphoratusmay provide a benefit as integrative medicine for the treatment of colon cancer.


2012 ◽  
Vol 34 (1) ◽  
pp. 61-69 ◽  
Author(s):  
Se-Kyoung Lee ◽  
Adeeb Shehzad ◽  
Jae-Chang Jung ◽  
Jong-Kyung Sonn ◽  
Jae-Tae Lee ◽  
...  

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1654 ◽  
Author(s):  
Olga Wesołowska ◽  
Krystyna Michalak ◽  
Maria Błaszczyk ◽  
Joseph Molnár ◽  
Kamila Środa-Pomianek

Multidrug resistance (MDR) that occurs in cancer cells constitutes one of the major reasons for chemotherapy failure. The main molecular mechanism of MDR is overexpression of protein transporters from the ATP-binding cassette (ABC) superfamily, such as ABCB1 (multidrug resistance protein 1 (MDR1), P-glycoprotein). At the expense of ATP hydrolysis, ABCB1 pumps a diverse range of substrates (including anticancer drugs) out of the cell, thereby reducing their intracellular concentration. In the present study, the ability of two patented disiloxanes (SILA-409 and SILA-421) to reverse drug resistance in human colon adenocarcinoma cell lines LoVo and LoVo/Dx was investigated. It was demonstrated that both compounds in concentrations of 0.5–1 µM strongly increased the sensitivity of LoVo/Dx cells to doxorubicin. By means of an accumulation test in which rhodamine 123 was used as an ABCB1 substrate analogue, both organosilicon compounds were also shown to inhibit ABCB1 transport activity. The intracellular accumulation of doxorubicin was also increased, and more drug entered the cellular nuclei of resistant cells in the presence of the studied compounds. In conclusion, both SILA-409 and SILA-421 were demonstrated to be effective MDR reversal agents in resistant human colon cancer cells.


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