Salinomycin inhibits Akt/NF-κB and induces apoptosis in cisplatin resistant ovarian cancer cells

Parajuli, Bidur; Lee, Hyun-Gyo; Kwon, Sang-Hoon; Cha, Soon-Do; Shin, So Jin; Lee, Gun-Ho; Bae, Insoo; Cho, Chi-Heum

doi:10.1016/j.canep.2013.02.008

Cited by 66 publications

(59 citation statements)

References 23 publications

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“…Each band is representative for three experiments by combination treatment compared with the expression by SVT or TRAIL-alone treatment. Salinomycin increased the expression of DR5, and Fas-associated protein with death domain (FADD) in cisplatin-resistant ovarian cancer cells (Parajuli et al 2013b). Another study reported that salinomycin inhibits the expression of NF-κB in cisplatin-resistant ovarian cancer cells (Parajuli et al 2013a).…”

Section: Discussionmentioning

confidence: 94%

“…Salinomycin increased the expression of DR5, and Fas-associated protein with death domain (FADD) in cisplatin-resistant ovarian cancer cells (Parajuli et al 2013b). Another study reported that salinomycin inhibits the expression of NF-κB in cisplatin-resistant ovarian cancer cells (Parajuli et al 2013a). Seleno-cyclodextrin sensitizes TRAIL-resistant human breast cancer cells to TRAIL-induced apoptosis through DR5 induction and NF-κB suppression (Lin et al 2011).…”

Section: Discussionmentioning

confidence: 94%

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Inhibitory effect of snake venom toxin on NF-κB activity prevents human cervical cancer cell growth via increase of death receptor 3 and 5 expression

et al. 2014

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We previously found that snake venom toxin inhibits nuclear factor kappa B (NF-κB) activity in several cancer cells. NF-κB is implicated in cancer cell growth and chemoresistance. In our present study, we investigated whether snake venom toxin (SVT) inhibits NF-κB, thereby preventing human cervical cancer cell growth (Ca Ski and C33A). SVT (0-12 μg/ml) inhibited the growth of cervical cancer cells by the induction of apoptotic cell death. These inhibitory effects were associated with the inhibition of NF-κB activity. However, SVT dose dependently increased the expression of death receptors (DRs): DR3, DR5 and DR downstream pro-apoptotic proteins. Exploration of NF-κB inhibitor (Phenylarsine oxide, 0.1 μM) synergistically further increased SVT-induced DR3 and DR5 expressions accompanied with further inhibition of cancer cells growth. Moreover, deletion of DR3 and DR5 by small interfering RNA significantly abolished SVT-induced cell growth inhibitory effects, as well as NF-κB inactivation. Using TNF-related apoptosis-inducing ligand resistance cancer cells (A549 and MCF-7), we also found that SVT enhanced the susceptibility of chemoresistance of these cancer cells through down-regulation of NF-κB, but up-regulation of DR3 and DR5. In vivo study also showed that SVT (0.5 and 1 mg/kg) inhibited tumor growth accompanied with inactivation of NF-κB. Thus, our present study indicates that SVT could be applicable as an anticancer agent for cervical cancer, or as an adjuvant agent for chemoresistant cancer cells.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 94%

Inhibitory effect of snake venom toxin on NF-κB activity prevents human cervical cancer cell growth via increase of death receptor 3 and 5 expression

et al. 2014

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“…The human ovarian cancer cell line OVCAR-3 was purchased from the American Type Culture Collection (Manassas, VA, USA) and was grown as a monolayer in RPMI 1640 medium supplemented with 1% (w/v) penicillin/streptomycin and 10% (v/v) fetal bovine serum (FBS) at 37˚C in a 5% CO 2 humidified atmosphere. The human ovarian cancer cell line A2780 and the cisplatin-resistant ovarian cancer cell line A2780cis were obtained from the European Collection of Animal Cell Cultures (Salisbury, UK) and maintained as described previously (11). PTX and cisplatin were purchased from Sigma-Aldrich (Merck Millipore, Darmstadt, Germany).…”

Section: Methodsmentioning

confidence: 99%

Hsp90 inhibitor SY-016 induces G2/M arrest and apoptosis in paclitaxel-resistant human ovarian cancer cells

et al. 2017

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Abstract. The aim of the present study was to evaluate the in vitro effect of a heat shock protein (Hsp)90 inhibitor, SY-016, on the paclitaxel (PTX)-resistant human ovarian cancer cell line OVCAR-3PTX, and explore its mechanism of apoptosis. In the present study, SY-016 was used in combination with PTX to determine its effect on the cell proliferation and apoptosis of OVCAR-3PTX cells. The drug-resistant tumor cells were established in vitro by stepwise sequential exposure to increasing concentrations of PTX. The cell viability and cell cycle distribution were measured by MTT assay and flow cytometric analysis, respectively. The induction of apoptosis was measured by caspase-3 activity, DNA fragmentation and western blot analyses. The cell viability significantly decreased following treatment with PTX and SY-016 as compared with either drug alone. The DNA fragmentation assay revealed an induction of apoptosis. The results from the flow cytometric analysis revealed an increase in the percentage of cells in the G2/M phase. Downregulation of B-cell lymphoma (Bcl)-2, X-linked inhibitor of apoptosis protein, survivin, Akt, nuclear factor-κB and cyclin-dependent kinase 4, as well as upregulation of Bcl-2-associated X protein, were observed. SY-016 may contribute to the induction of apoptosis in OVCAR-3PTX cells. These results suggest that SY-016 in combination with PTX may be a beneficial chemotherapeutic strategy, particularly in patients with tumors refractory to PTX.

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“…Binding of DR5 to its ligand leads to alterations in death domain (DD, part of the caspase), mobilizing the enzymatic cascade which results in the death of the cell. 23 Another mechanism of apoptosis in the ovarian cancer cells resistant to cisplatin involves the inhibitory effect of salinomycin on the nuclear transcription factor NF-kB, which affects the control of several other genes. 24 In practice, salinomycin is also being used by prof. Cord Naujokat in Heidelberg, Germany, obtaining good results among invasive carcinoma in screening studies.…”

Section: Salinomycinmentioning

confidence: 99%

“…23 Another mechanism of apoptosis in the ovarian cancer cells resistant to cisplatin involves the inhibitory effect of salinomycin on the nuclear transcription factor NF-kB, which affects the control of several other genes. 24 In practice, salinomycin is also being used by prof. Cord Naujokat in Heidelberg, Germany, obtaining good results among invasive carcinoma in screening studies. The administration of salinomycin has resulted in the inhibition of disease progress over an extended period of time.…”

Section: Salinomycinmentioning

confidence: 99%

Ovarian cancer stem cells: A target for oncological therapy

Markowska¹,

Sajdak²,

Huczyński³

et al. 2018

Adv Clin Exp Med

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According to numerous studies, failures in treatment of ovarian cancer, i.e., a relapse and metastases, result from a small population of cancer stem cells (CSCs). They may also be responsible for tumor initiation. Cancer stem cells are resistant to chemo-and radiotherapy. Eradication of CSCs may involve the application of salinomycin, metformin and Clostridium perfringens; the effect of anti-angiogenic factors remains controversial. Salinomycin is an antibiotic isolated from Streptomyces albus bacteria. Its CSC-eradicating effect has been demonstrated both in ovarian cancer cell lines and in women with breast cancer. Clostridium perfringens enterotoxin (CPE) has been demonstrated to destroy CSCs in ovarian cancer both in vivo and in vitro. Metformin, apart from its hypoglycemic effect, reduces the CSC population and inhibits the proliferation of neoplastic cells and angiogenesis. Cancer stem cells with expression of VEGFR1+ have been described as affecting circulating cancer cells and influencing the formation of metastases. Both positive and negative effects of anti-angiogenic therapy on the CSC population have been documented.

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Salinomycin inhibits Akt/NF-κB and induces apoptosis in cisplatin resistant ovarian cancer cells

Cited by 66 publications

References 23 publications

Inhibitory effect of snake venom toxin on NF-κB activity prevents human cervical cancer cell growth via increase of death receptor 3 and 5 expression

Inhibitory effect of snake venom toxin on NF-κB activity prevents human cervical cancer cell growth via increase of death receptor 3 and 5 expression

Hsp90 inhibitor SY-016 induces G2/M arrest and apoptosis in paclitaxel-resistant human ovarian cancer cells

Ovarian cancer stem cells: A target for oncological therapy

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