Spheres from cervical cancer cells display stemness and cancer drug resistance

Liu, Huan; Wang, Haijuan; Li, Chunxiao; Zhang, Tingting; Meng, Xuan; Zhang, Ying; Qian, Haili

doi:10.3892/ol.2016.4893

Cited by 15 publications

(12 citation statements)

References 22 publications

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“…Thus, further studies are important to clarify the potential of the ABCG2 transporter in anti‐cancer drug efflux dependent on cellular conditions such as adherent and 3D culture. Previous reports have shown that 3D culture conditions induce cancer cells to develop CSC phenotypes such as high expression of CSC markers and anti‐cancer drug resistance in some cancer cells . In the same fashion, PDAC cells converted into ABCG2+ cells possessing stemness and anti‐cancer drug resistance by 3D culture conditions in this study.…”

Section: Discussionsupporting

confidence: 72%

Stemness and anti‐cancer drug resistance in ATP‐binding cassette subfamily G member 2 highly expressed pancreatic cancer is induced in 3D culture conditions

et al. 2018

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The expression of ATP‐binding cassette subfamily G member 2 (ABCG2) is related to tumorigenic cancer stem cells (CSC) in several cancers. However, the effects of ABCG2 on CSC‐related malignant characteristics in pancreatic ductal adenocarcinoma (PDAC) are not well elucidated. In this study, we compared the characteristics of low (ABCG2−) and high (ABCG2+)‐ABCG2‐expressing PDAC cells after cell sorting. In adherent culture condition, human PDAC cells, PANC‐1, contained approximately 10% ABCG2+ cell populations, and ABCG2+ cells displayed more and longer microvilli compared with ABCG2− cells. Unexpectedly, ABCG2+ cells did not show significant drug resistance against fluorouracil, gemcitabine and vincristine, and ABCG2− cells exhibited higher sphere formation ability and stemness marker expression than those of ABCG2+ cells. Cell growth and motility was greater in ABCG2− cells compared with ABCG2+ cells. In contrast, epithelial‐mesenchymal transition ability between ABCG2− and ABCG2+ cells was comparable. In 3D culture conditions, spheres derived from ABCG2− cells generated a large number of ABCG2+ cells, and the expression levels of stemness markers in these spheres were higher than spheres from ABCG2+ cells. Furthermore, spheres containing large populations of ABCG2+ cells exhibited high resistance against anti‐cancer drugs presumably depending on ABCG2. ABCG2+ cells in PDAC in adherent culture are not correlated with stemness and malignant behaviors, but ABCG2+ cells derived from ABCG2− cells after sphere formation have stemness characteristics and anti‐cancer drug resistance. These findings suggest that ABCG2− cells generate ABCG2+ cells and the malignant potential of ABCG2+ cells in PDAC varies depending on their environments.

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Section: Discussionsupporting

confidence: 72%

Stemness and anti‐cancer drug resistance in ATP‐binding cassette subfamily G member 2 highly expressed pancreatic cancer is induced in 3D culture conditions

et al. 2018

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“…Cervical cancer is one of the most common malignancies diagnosed in women [ 173 , 174 , 175 ]. Chronic infection with high-risk human papillomavirus and inherited polymorphism of cytokine genes are involved in cervical cancer emergence [ 176 , 177 , 178 , 179 , 180 ].…”

Section: Chrysin and Cancermentioning

confidence: 99%

Broad-Spectrum Preclinical Antitumor Activity of Chrysin: Current Trends and Future Perspectives

et al. 2020

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Pharmacological profile of phytochemicals has attracted much attention to their use in disease therapy. Since cancer is a major problem for public health with high mortality and morbidity worldwide, experiments have focused on revealing the anti-tumor activity of natural products. Flavonoids comprise a large family of natural products with different categories. Chrysin is a hydroxylated flavonoid belonging to the flavone category. Chrysin has demonstrated great potential in treating different disorders, due to possessing biological and therapeutic activities, such as antioxidant, anti-inflammatory, hepatoprotective, neuroprotective, etc. Over recent years, the anti-tumor activity of chrysin has been investigated, and in the present review, we provide a mechanistic discussion of the inhibitory effect of chrysin on proliferation and invasion of different cancer cells. Molecular pathways, such as Notch1, microRNAs, signal transducer and activator of transcription 3 (STAT3), nuclear factor-kappaB (NF-κB), PI3K/Akt, MAPK, etc., as targets of chrysin are discussed. The efficiency of chrysin in promoting anti-tumor activity of chemotherapeutic agents and suppressing drug resistance is described. Moreover, poor bioavailability, as one of the drawbacks of chrysin, is improved using various nanocarriers, such as micelles, polymeric nanoparticles, etc. This updated review will provide a direction for further studies in evaluating the anti-tumor activity of chrysin.

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“…Moreover, in many underdeveloped countries routine screening may not be widely available due to limited resources ( Denny et al, 2006 ). Although new chemotherapeutic agents have been developed to slow down the progression of the disease, the number of cancer related deaths is still high because of drug-resistance and metastasis ( Liu et al, 2016 ; Siegel et al, 2016 ). Also, conventional treatments for cervical cancer are expensive ( Subramanian et al, 2010 ).…”

Section: Introductionmentioning

confidence: 99%

Kaempferia parviflora Extract Exhibits Anti-cancer Activity against HeLa Cervical Cancer Cells

et al. 2017

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Kaempferia parviflora (KP) has been traditionally used as a folk remedy to treat several diseases including cancer, and several studies have reported cytotoxic activities of extracts of KP against a number of different cancer cell lines. However, many aspects of the molecular mechanism of action of KP remain unclear. In particular, the ability of KP to regulate cancer cell growth and survival signaling is still largely unexplored. The current study aimed to investigate the effects of KP on cell viability, cell migration, cell invasion, cell apoptosis, and on signaling pathways related to growth and survival of cervical cancer cells, HeLa. We discovered that KP reduced HeLa cell viability in a concentration-dependent manner. The potent cytotoxicity of KP against HeLa cells was associated with a dose-dependent induction of apoptotic cell death as determined by flow cytometry and observation of nuclear fragmentation. Moreover, KP-induced cell apoptosis was likely to be mediated through the intrinsic apoptosis pathway since caspase 9 and caspase 7, but not BID, were shown to be activated after KP exposure. Based on the observation that KP induced apoptosis in HeLa cell, we further investigated the effects of KP at non-cytotoxic concentrations on suppressing signal transduction pathways relevant to cell growth and survival. We found that KP suppressed the MAPK and PI3K/AKT signaling pathways in cells activated with EGF, as observed by a significant decrease in phosphorylation of ERK1/2, Elk1, PI3K, and AKT. The data suggest that KP interferes with the growth and survival of HeLa cells. Consistent with the inhibitory effect on EGF-stimulated signaling, KP potently suppressed the migration of HeLa cells. Concomitantly, KP was demonstrated to markedly inhibit HeLa cell invasion. The ability of KP in suppressing the migration and invasion of HeLa cells was associated with the suppression of matrix metalloproteinase-2 production. These data strongly suggest that KP may slow tumor progression and metastasis in patients with cervical cancer. Taken together, the present report provides accumulated evidence revealing the potent anti-cancer activities of Kaempferia parviflora against cervical cancer HeLa cells, and suggests its potential use as an alternative way for cervical cancer prevention and therapy.

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Spheres from cervical cancer cells display stemness and cancer drug resistance

Cited by 15 publications

References 22 publications

Stemness and anti‐cancer drug resistance in ATP‐binding cassette subfamily G member 2 highly expressed pancreatic cancer is induced in 3D culture conditions

Stemness and anti‐cancer drug resistance in ATP‐binding cassette subfamily G member 2 highly expressed pancreatic cancer is induced in 3D culture conditions

Broad-Spectrum Preclinical Antitumor Activity of Chrysin: Current Trends and Future Perspectives

Kaempferia parviflora Extract Exhibits Anti-cancer Activity against HeLa Cervical Cancer Cells

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