Effects of paclitaxel on permanent head and neck squamous cell carcinoma cell lines and identification of anti-apoptotic caspase 9b

Maushagen, Regina; Reers, Stefan; Pfannerstill, Ann-Christin; Hahlbrock, Angelina; Stauber, Roland H.; Rahmanzadeh, Ramtin; Rades, Dirk; Pries, Ralph; Wollenberg, Barbara

doi:10.1007/s00432-016-2150-3

Cited by 12 publications

(10 citation statements)

References 34 publications

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“…Paclitaxel (PTX; Fig. 1A), a first-line therapeutic agent used clinically to treat breast cancer, exerts its antitumor activity by promoting the polymerization of tubulin and stabilizing the resulting micro-tubules, causing cell cycle arrest at the G2/M phase that leads to apoptotic death of cancer cells (3). However, paclitaxel resistance often occurs after a period of treatment, causing a serious problem in chemotherapy (4).…”

Section: Introductionmentioning

confidence: 99%

SB-T-121205, a next-generation taxane, enhances apoptosis and inhibits migration/invasion in MCF-7/PTX cells

Zheng

Wang

Yang

et al. 2017

International Journal of Oncology

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Breast cancer is the leading cause of cancer death among women. Paclitaxel, a mitotic inhibitor, is highly effective in the treatment of breast cancer. However, development of resistance to paclitaxel limits its clinical use. Identifying new compounds and new strategies that are effective against breast cancer, in particular drug-resistant cancer, is of great importance. The aim of the present study was to explore the potential of a next-generation taxoid, SB-T-121205, in modulating the proliferation, migration and invasion of paclitaxel-resistant human breast cancer cells (MCF-7/PTX) and further evaluate the underlying molecular mechanisms. The results of MTT assay showed that SB-T-121205 has much higher potency to human breast cancer cells (MCF-7/S, MCF-7/PTX and MDA-MB-453 cells) than paclitaxel, while that the non-tumorigenic human bronchial epithelial cells (BEAS-2B) were slightly less sensitive to SB-T-121205 than paclitaxel. Flow cytometry and western blot methods revealed that SB-T-121205 induced cell cycle arrest at the G2/M phase and apoptosis in MCF-7/PTX cells through accelerating mitochondrial apoptotic pathway, resulting in reduction of Bcl-2/Bax ratio, as well as elevation of caspase-3, caspase-9, and poly(ADP-ribose) polymerase (PARP) levels. Moreover, SB-T-121205 changed epithelial-mesenchymal transition (EMT) property, and suppressed migration and invasion abilities of MCF-7/PTX cells. Additionally, SB-T-121205 exerted antitumor activity by inhibiting the transgelin 2 and PI3K/Akt pathway. These findings indicate that SB-T-121205 is a potent antitumor agent that promotes apoptosis and also recedes migration/invasion abilities of MCF-7/PTX cells by restraining the activity of transgelin 2 and PI3K/Akt, as well as mitochondrial apoptotic pathway. Such results suggest a potential clinical value of SB-T-121205 in breast cancer treatment.

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Section: Introductionmentioning

confidence: 99%

SB-T-121205, a next-generation taxane, enhances apoptosis and inhibits migration/invasion in MCF-7/PTX cells

Zheng

Wang

Yang

et al. 2017

International Journal of Oncology

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“…For primary keratinocyte cultures, keratinocytes are grown on feeder cells (mouse fibroblasts) in 2-D and have a limited lifespan. In vitro drug screens of 2-D lines have been used to characterize variability in drug response among tumors and as a tool to understand resistance mechanisms of tumor cells (8,9). In an attempt to overcome limitations of these 2-D systems (10,11), HNSCC lines have been replated in a three-dimensional (3-D) format.…”

Section: July 2019 Cancer Discovery | 853mentioning

confidence: 99%

Oral Mucosal Organoids as a Potential Platform for Personalized Cancer Therapy

et al. 2019

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Previous studies have described that tumor organoids can capture the diversity of defined human carcinoma types. Here, we describe conditions for long-term culture of human mucosal organoids. Using this protocol, a panel of 31 head and neck squamous cell carcinoma (HNSCC)-derived organoid lines was established. This panel recapitulates genetic and molecular characteristics previously described for HNSCC. Organoids retain their tumorigenic potential upon xenotransplantation. We observe differential responses to a panel of drugs including cisplatin, carboplatin, cetuximab, and radiotherapy in vitro. Additionally, drug screens reveal selective sensitivity to targeted drugs that are not normally used in the treatment of patients with HNSCC. These observations may inspire a personalized approach to the management of HNSCC and expand the repertoire of HNSCC drugs. SIGNIFICANCE: This work describes the culture of organoids derived from HNSCC and corresponding normal epithelium. These tumoroids recapitulate the disease genetically, histologically, and functionally. In vitro drug screening of tumoroids reveals responses to therapies both currently used in the treatment of HNSCC and those not (yet) used in clinical practice.

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“…To uncover its inhibition mechanism, 1 was first subjected to flow cytometry. According to a previous study, Paclitaxel can induce apoptosis via arresting cells mainly in the G2/M phase of the cell cycle (Jelinek et al, 2015; Maushagen et al, 2016). Therefore, it was used as the positive control.…”

Section: Resultsmentioning

confidence: 98%

Andrastone A From the Deep-Sea-Derived Fungus Penicillium allii-sativi Acts as an Inducer of Caspase and RXRα-Dependent Apoptosis

et al. 2019

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Two new (1, 2) and one known (3) meroterpenoids were isolated from the deep-sea-derived fungus Penicillium allii-sativi. The relative structures of new compounds were determined on the basis of an extensive analysis of the NMR and MS data, and the absolute configurations were established by ECD calculations. Andrastone A (1) is a rare andrastin bearing an unusual cyclopentan-1,3-dione. It shows a selectively antiproliferative effect against HepG2 tumor cells with an IC50 value of 7.8 μM. Mechanism study showed that apoptosis via Caspase and RXRα pathways are responsible for the inhibitory effect.

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Effects of paclitaxel on permanent head and neck squamous cell carcinoma cell lines and identification of anti-apoptotic caspase 9b

Abstract: Our data indicate the presence of anti-apoptotic caspase 9b in HNSCC, which may serve as a promising target to increase chemotherapeutic apoptosis induction.

Cited by 12 publications

References 34 publications

SB-T-121205, a next-generation taxane, enhances apoptosis and inhibits migration/invasion in MCF-7/PTX cells

SB-T-121205, a next-generation taxane, enhances apoptosis and inhibits migration/invasion in MCF-7/PTX cells

Oral Mucosal Organoids as a Potential Platform for Personalized Cancer Therapy

Andrastone A From the Deep-Sea-Derived Fungus Penicillium allii-sativi Acts as an Inducer of Caspase and RXRα-Dependent Apoptosis

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