Anticancer Activity of Some Ruthenium (III) Complexes with Quinolone Antibiotics: In Vitro Cytotoxicity, Cell Cycle Modulation, and Apoptosis-Inducing Properties in LoVo Colon Cancer Cell Line

Cisplatin is one of the most effective anticancer agents used to treat colon cancer, which is the third malignancy between the most common human cancers in the world, but the resistance developed represents an obstacle against the full success of chemotherapy. An emerging interest appeared in finding other metallic compounds, such as ruthenium(III) complexes, for chemotherapeutic application in cancer. Our study focused on the anticancer activity of several ruthenium (Ru) complexes with quinolone antibiotics in colon tumor cell cultures. Real-time cell analysis and drug-mediated cytotoxicity tests monitored the inhibitory effects in the drug-treated LoVo colon cancer cells. Flow cytometry assays were performed to evaluate cell cycle phases distribution and apoptotic events. The obtained results showed dose-dependent increased levels of cell lysis and induction of apoptosis in LoVo cancer cells treated with the Ru(III) complexes. In addition, data showed a major decrease in cell proliferation, since the percentages of cells distributed in the S cell cycle phase diminished, and a G0/G1 cell arrest was observed. Therefore, our results strongly suggest that the newly synthesized Ru(III) complexes might play an important role in future chemotherapeutic approaches, since their activity is based on diminishing cell proliferation, induction of apoptosis, and modulation of cell cycle phases.

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Pro-Apoptotic Activity of Artichoke Leaf Extracts in Human HT-29 and RKO Colon Cancer Cells

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18084166 ◽

2021 ◽

Vol 18 (8) ◽

pp. 4166

Author(s):

Milena Villarini ◽

Mattia Acito ◽

Raffaella di Vito ◽

Samuele Vannini ◽

Luca Dominici ◽

...

Keyword(s):

Cell Cycle ◽

Colon Cancer ◽

Chlorogenic Acid ◽

Cancer Cells ◽

Herbaceous Plant ◽

Colon Cancer Cells ◽

Leaf Extracts ◽

Caffeoylquinic Acids ◽

Induction Of Apoptosis ◽

Ht 29

(1) Background: Cynara cardunculus L. subsp. scolymus (L.) Hegi, popularly known as artichoke, is an herbaceous plant belonging to the Asteraceae family. Artichoke leaf extracts (ALEs) have been widely used in traditional medicine because of their hepatoprotective, cholagogic, hypoglycaemic, hypolipemic and antibacterial properties. ALEs are also recognized for their antioxidative and anti-inflammatory activities. In this study, we evaluated the cytotoxic, genotoxic, and apoptotic activities, as well as effect on cell growth of ALEs on human colon cancer HT-29 and RKO cells. HT-29 and RKO cells exhibit a different p53 status: RKO cells express the wild-type protein, whereas HT-29 cells express a p53-R273H contact mutant. (2) Methods: Four different ALEs were obtained by sequential extraction of dried artichoke leaves; ALEs were characterized for their content in chlorogenic acid, cynaropicrin, and caffeoylquinic acids. HT-29 and RKO cells were used for in vitro testing (i.e., cytotoxicity and genotoxicity assessment, cell cycle analysis, apoptosis induction). (3) Results: Two out of the four tested ALEs showed marked effects on cell vitality toward HT-29 and RKO tumour cells. The effect was accompanied by a genotoxic activity exerted at a non-cytotoxic concentrations, by a significant perturbation of cell cycle (i.e., with increase of cells in the sub-G1 phase), and by the induction of apoptosis. (4) Conclusions: ALEs rich in cynaropicrin, caffeoylquinic acids, and chlorogenic acid showed to be capable of affecting HT-29 and RKO colon cancer cells by inducing favourable biological effects: cell cycle perturbation, activation of mitochondrial dependent pathway of apoptosis, and the induction of genotoxic effects probably mediated by the induction of apoptosis. Taken together, these results weigh in favour of a potential cancer chemotherapeutic activity of ALEs.

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Itraconazole inhibits the Hedgehog signaling pathway thereby inducing autophagy-mediated apoptosis of colon cancer cells

Cell Death and Disease ◽

10.1038/s41419-020-02742-0 ◽

2020 ◽

Vol 11 (7) ◽

Cited By ~ 1

Author(s):

Huiming Deng ◽

Ling Huang ◽

Zhongkai Liao ◽

Mi Liu ◽

Qiang Li ◽

...

Keyword(s):

Cell Cycle ◽

Colon Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Signaling Pathway ◽

Hedgehog Signaling ◽

Colon Cancer Cell ◽

Hedgehog Signaling Pathway ◽

Colon Cancer Cells ◽

Hct 116

AbstractItraconazole is as an antifungal medication used to treat systemic fungal infections. Recently, it has been reported to be effective in suppressing tumor growth by inhibiting the Hedgehog signaling pathway and angiogenesis. In the present study, we investigated whether itraconazole induces autophagy-mediated cell death of colon cancer cells through the Hedgehog signaling pathway. Cell apoptosis and cell cycle distribution of the colon cancer cell lines SW-480 and HCT-116 were detected by flow cytometry and terminal TUNEL assay. Autophagy and signal proteins were detected by western blotting and cell proliferation-associated antigen Ki-67 was measured using immunohistochemistry. The images of autophagy flux and formation of autophagosomes were observed by laser scanning confocal and/or transmission electron microscopy. Colon cancer cell xenograft mouse models were also established. Itraconazole treatment inhibited cell proliferation via G1 cell cycle arrest as well as autophagy-mediated apoptosis of SW-480 and HCT-116 colon cancer cells. In addition, the Hedgehog pathway was found to be involved in activation of itraconazole-mediated autophagy. After using the Hedgehog agonist recombinant human Sonic Hedgehog (rhshh), itraconazole could counteract the activation of rhshh. Moreover, treatment with itraconazole produced significant cancer inhibition in HCT-116-bearing mice. Thus, itraconazole may be a potential and effective therapy for the treatment of colon cancer.

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Identification of Nrf2/STAT3 axis in induction of apoptosis through sub‐G 1 cell cycle arrest mechanism in HT‐29 colon cancer cells

Journal of Cellular Biochemistry ◽

10.1002/jcb.28678 ◽

2019 ◽

Vol 120 (8) ◽

pp. 14035-14043 ◽

Cited By ~ 7

Author(s):

Issa Tajmohammadi ◽

Jamal Mohammadian ◽

Mehdi Sabzichi ◽

Shiva Mahmuodi ◽

Mina Ramezani ◽

...

Keyword(s):

Cell Cycle ◽

Colon Cancer ◽

Cell Cycle Arrest ◽

Cancer Cells ◽

Colon Cancer Cells ◽

Cycle Arrest ◽

Induction Of Apoptosis ◽

Ht 29

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Chitosan exerts anticancer activity through induction of apoptosis and cell cycle arrest in oral cancer cells

Journal of Oral Science ◽

10.2334/josnusd.56.119 ◽

2014 ◽

Vol 56 (2) ◽

pp. 119-126 ◽

Cited By ~ 33

Author(s):

Yuniardini S. Wimardhani ◽

Dewi F. Suniarti ◽

Hans J. Freisleben ◽

Septelia I. Wanandi ◽

Nurjati C. Siregar ◽

...

Keyword(s):

Cell Cycle ◽

Oral Cancer ◽

Anticancer Activity ◽

Cell Cycle Arrest ◽

Cancer Cells ◽

Cycle Arrest ◽

Induction Of Apoptosis ◽

Oral Cancer Cells

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Deguelin inhibits the growth of colon cancer cells through the induction of apoptosis and cell cycle arrest

European Journal of Cancer ◽

10.1016/s0959-8049(02)00192-2 ◽

2002 ◽

Vol 38 (18) ◽

pp. 2446-2454 ◽

Cited By ~ 62

Author(s):

G Murillo ◽

G.I Salti ◽

J.W Kosmeder II ◽

J.M Pezzuto ◽

R.G Mehta

Keyword(s):

Cell Cycle ◽

Colon Cancer ◽

Cell Cycle Arrest ◽

Cancer Cells ◽

Colon Cancer Cells ◽

Cycle Arrest ◽

Induction Of Apoptosis

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Cell cycle arrest following pan-RAS inhibition can occur through upregulation of p27 in both KRAS-dependent and KRAS-independent colon cancer cell lines

10.1101/2020.12.08.416578 ◽

2020 ◽

Author(s):

Caleb K. Stubbs ◽

Marco Biancucci ◽

Vania Vidimar ◽

Karla J. F. Satchell

Keyword(s):

Cell Cycle ◽

Colon Cancer ◽

Cell Proliferation ◽

Growth Inhibition ◽

Cell Cycle Arrest ◽

Cancer Cells ◽

Cell Lines ◽

Ras Signaling ◽

Colon Cancer Cells ◽

Cycle Arrest

ABSTRACTRAS is one of the most frequently mutated oncogenes in cancer with ~30% of all human tumors harboring a mutation in either HRAS, NRAS, or KRAS isoforms. Despite countless efforts for development of small molecule inhibitors for RAS, it remains an elusive target in the clinic. Here we demonstrated that the pan-RAS biological inhibitor RAS/RAP1-specific endopeptidase (RRSP) has proteolytic activity in ‘Ras-less’ mouse embryonic fibroblasts expressing human RAS isoforms (H/N/KRAS) or major oncogenic KRAS mutants (G12C, G12V, G12D, G13D, and Q61R). The cleavage of RAS inhibited phosphorylation of ERK and cell proliferation. To investigate how RAS processing affects colon cancer cells, we tested RRSP against KRAS-dependent (SW620 and GP5d) and KRAS-independent (HCT-116, SW1463, and HT-29) cell lines and found that RRSP inhibited growth. The cleavage of RAS was cytotoxic in some cell lines and induced either irreversible cell cycle arrest or uncharacterized growth inhibition in others. The G1 cell cycle arrest in some colon cancer cells was mediated through rescue of p27 (Kip1) protein expression resulting in reduced phosphorylation of retinoblastoma protein. Together, this work demonstrated that complete ablation of RAS in cells induces growth inhibition, but the mechanism of inhibition can vary in different tumor cell lines. This ability of RAS processing to halt cell proliferation by multiple strategies highlights RRSP both as a potential anti-tumor therapy and as a tool for studying RAS signaling across tumor types.

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