SH003 enhances paclitaxel chemosensitivity in MCF-7/PAX breast cancer cells through inhibition of MDR1 activity

Choi, Ha Na; Cho, Sung Gook; Kim, Min Kyoung; Lee, Hee Jae; Moon, Seung Hee; Jang, Hee Jae; Ko, Seong‐Gyu

doi:10.1007/s11010-016-2875-y

Cited by 23 publications

(22 citation statements)

References 36 publications

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“…In line with this, both untreated and PTX-treated PTX-res MCF-7 cells showed a significant MDR1/ABCB1 protein expression profile compared to wt cells [ 26 ] ( Figure 1 B). Similar to our findings, PTX-res MCF-7 cells showed increased MDR1 activation and protein expression levels linked with the EMT signaling pathway [ 27 ]. The wt MCF-7 cells showed an epithelial cell profile with their apicobasal polarity formation and close contact with each other.…”

Section: Discussionsupporting

confidence: 91%

Specific c-Jun N-Terminal Kinase Inhibitor, JNK-IN-8 Suppresses Mesenchymal Profile of PTX-Resistant MCF-7 Cells through Modulating PI3K/Akt, MAPK and Wnt Signaling Pathways

Kilbas

Sönmez

Uysal-Onganer

et al. 2020

Biology

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Paclitaxel (PTX) is a widely used chemotherapeutic agent in the treatment of breast cancer, and resistance to PTX is a common failure of breast cancer therapy. Therefore, understanding the effective molecular targets in PTX-resistance gains importance in identifying novel strategies in successful breast cancer therapy approaches. The aim of the study was to investigate the functional role of PTX resistance on MCF-7 cell survival and proliferation related to PI3K/Akt and MAPK pathways. The generated PTX-resistant (PTX-res) MCF-7 cells showed enhanced cell survival, proliferation, and colony formation potential with decreased cell death compared to wt MCF-7 cells. PTX-res MCF-7 cells exhibited increased motility profile with EMT, PI3K/Akt, and MAPK pathway induction. According to the significant SAPK/JNK activation in PTX-res MCF-7 cells, specific c-Jun N-terminal kinase inhibitor, JNK-IN-8 is shown to suppress the migration potential of cells. Treatment of JNK inhibitor suppressed the p38 and SAPK/JNK and Vimentin expression. However, the JNK inhibitor further downregulated Wnt signaling members in PTX-res MCF-7 cells. Therefore, the JNK inhibitor JNK-IN-8 might be used as a potential therapy model to reverse PTX-resistance related to Wnt signaling.

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Section: Discussionsupporting

confidence: 91%

Specific c-Jun N-Terminal Kinase Inhibitor, JNK-IN-8 Suppresses Mesenchymal Profile of PTX-Resistant MCF-7 Cells through Modulating PI3K/Akt, MAPK and Wnt Signaling Pathways

Kilbas

Sönmez

Uysal-Onganer

et al. 2020

Biology

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“…The chemotherapy response in various cancer patients is frequently compromised by drug insensitivity, which eventually leads to treatment failure [33, 34]. Numerous genes associated with the drug sensitivity of chemotherapy have been identified [35].…”

Section: Discussionmentioning

confidence: 99%

Osterix Decreases the Chemosensitivity of Breast Cancer Cells by Upregulating GALNT14

Chen

Bao

et al. 2017

Cell Physiol Biochem

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Background/Aims: Osterix (Osx), a key regulator of osteoblast differentiation and bone formation, has been recently reported to be associated with the progression of breast cancer. However, the precise roles of Osx in breast cancer remain unclear. Methods: Drug sensitivity of the cancer cells was assessed using an 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Target genes were obtained by high-throughput Illumina sequencing and were confirmed in vitro and in vivo. Apoptosis was analysed by Hoechst staining and western blotting. A tissue microarray including 129 samples from breast cancer patients was used for immunohistochemistry (IHC) assays. Results: Overexpression of Osx decreased the chemosensitivity of breast cancer cells, while knockdown of Osx increased the chemosensitivity of breast cancer cells. In particular, we found that the decreased chemosensitivity effect was significantly associated with elevated expression of the polypeptide N-acetylgalactosaminyltransferase 14 (GALNT14). Silencing of GALNT14 in Osx-overexpressed cells restored the decreased chemosensitivity. Conversely, overexpression of GALNT14 in Osx-knockdown cells abrogated the increased chemosensitivity in breast cancer cells. In addition, we revealed that Osx decreased GALNT14-dependent chemosensitivity by enhancing anti-apoptosis. GALNT14 expression exhibited a significant association with breast cancer stages as well as the disease-free survival (DFS) rate. Conclusion: Osx plays an important role in the chemosensitivity and inhibition of Osx expression may represent a therapeutic strategy to enhance the chemosensitivity of breast cancer.

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“…The present study administered SH003 alone; however, the results of experimental studies on the efficacy of the combined treatment of SH003 and anticancer drugs including doxorubicin and paclitaxel have been reported. 23,24 We are also interested in combination therapy and have received investigational new drug approval from the Ministry of Food and Drug Safety (MFDS) for a Phase 1/2 clinical trial of combination therapy. Several preclinical studies have shown that SH003 has an anticancer effect on breast cancer.…”

Section: Discussionmentioning

confidence: 99%

A Phase I Study to Evaluate the Safety of the Herbal Medicine SH003 in Patients With Solid Cancer

Cheon

2020

Integr Cancer Ther

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Background: Cancer is a major health problem worldwide and the leading cause of death in many countries. Preclinical studies have shown the therapeutic anticancer effects of SH003, a novel herbal medicine containing Astragalus membranaceus, Angelica gigas, and Trichosanthes kirilowii. The present study investigated the maximum tolerated dose of SH003 in patients with solid cancers. Methods: This open-label, dose-escalation trial used the traditional 3 + 3 dose-escalation design. Patients with solid cancers were recruited and administered 1 to 4 tablets of SH003 thrice daily for 3 weeks according to the dose level. Adverse events were evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE). Dose-limiting toxicities (DLTs) were defined as Grade 3 or higher adverse events based on CTCAE. The maximum tolerated dose was defined as the highest dose at which no more than 1 of 6 patients experienced DLT. Results: The present study enrolled 11 patients. A total of 31 adverse events occurred. According to the CTCAE, all the observed adverse events were grade 2 or less and no adverse events of grade 3 or more corresponding to DLT occurred. Conclusion: The study results indicated that the maximum tolerated dose of SH003 was 4800 mg/day. A Phase 2 study is required to determine the efficacy of SH003 in patients with cancer at a dose of 4800 mg/day or less.

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SH003 enhances paclitaxel chemosensitivity in MCF-7/PAX breast cancer cells through inhibition of MDR1 activity

Cited by 23 publications

References 36 publications

Specific c-Jun N-Terminal Kinase Inhibitor, JNK-IN-8 Suppresses Mesenchymal Profile of PTX-Resistant MCF-7 Cells through Modulating PI3K/Akt, MAPK and Wnt Signaling Pathways

Specific c-Jun N-Terminal Kinase Inhibitor, JNK-IN-8 Suppresses Mesenchymal Profile of PTX-Resistant MCF-7 Cells through Modulating PI3K/Akt, MAPK and Wnt Signaling Pathways

Osterix Decreases the Chemosensitivity of Breast Cancer Cells by Upregulating GALNT14

A Phase I Study to Evaluate the Safety of the Herbal Medicine SH003 in Patients With Solid Cancer

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