Antitumor activity of β-2-himachalen-6-ol in colon cancer is mediated through its inhibition of the PI3K and MAPK pathways

Daaboul, Hamid Elia; Daher, Costantine F.; Bodman‐Smith, Kikki; Taleb, Robin I.; Shebaby, Wassim N.; Boulos, Joelle C.; Dagher, Carole; Mroueh, Mohamad; El‐Sibai, Mirvat

doi:10.1016/j.cbi.2017.08.003

Cited by 28 publications

(23 citation statements)

References 28 publications

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“…To our best knowledge, the regulation of AMPK and PI3K/AKT pathways are complicated. On the basis of several previous researches [35,36], we speculated that miR-622 affected AMPK and PI3K/AKT pathways might through adjusting the up-stream interrelated genes expression of these two pathways. Further researches are still necessary to probe this issue.…”

Section: Discussionmentioning

confidence: 98%

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RETRACTED ARTICLE: Silencing UNC5B antisense lncRNA 1 represses growth and metastasis of human Colon cancer cells via raising miR-622

Zhang

Lan

2019

Artificial Cells, Nanomedicine, and Biotechnology

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Background: Colon cancer is the most frequently lethal cancer in digestive system. Herein, we tested the influences of UNC5B antisense lncRNA 1 (UNC5B-AS1) on colon cancer cell growth and metastasis, along with the regulatory function of UNC5B-AS1 in microRNA-622 (miR-622) expression. Methods: Firstly, UNC5B-AS1 expression in colon cancer tissues and corresponding normal tissues were tested. Then, the influences of silencing UNC5B-AS1 by sh-UNC5B-AS1 transfection on colon cancer HCT116 and Caco-2 cell viability, proliferation, migration, invasion and apoptosis, as well as miR-622 expression were assessed, respectively. Subsequently, whether miR-622 attended to the influences of silencing UNC5B-AS1 on HCT116 and Caco-2 cells were probed. Finally, the activities of AMPK and PI3K/AKT pathways in cells were analysed. Results: UNC5B-AS1 had high expression level in colon cancer tissues. Silencing UNC5B-AS1 repressed HCT116 and Caco-2 cell proliferation, migration and invasion, but boosted cell apoptosis. Moreover, silencing UNC5B-AS1 raised miR-622 expression in HCT116 and Caco-2 cells. miR-622 inhibitor transfection weakened the influences of silencing UNC5B-AS1 on HCT116 and Caco-2 cells. Besides, Silencing UNC5B-AS1 suppressed AMPK and PI3K/AKT pathways via raising miR-622. Conclusion: Silencing UNC5B-AS1 repressed colon cancer growth and metastasis might be through raising miR-622 expression and suppressing AMPK and PI3K/AKT pathways.

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Section: Discussionmentioning

confidence: 98%

“…AMPK and PI3K/AKT pathways are proved to be activated in colon cancer [32,33]. It is reported that unusual activations of AMPK and PI3K/AKT pathways contribute to growth, metastasis and drug resistance of colon cancer [34][35][36]. Hereon, silencing UNC5B-AS1 hampered AMPK and PI3K/AKT pathways in HCT116 and Caco-2 cells.…”

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Silencing UNC5B antisense lncRNA 1 represses growth and metastasis of human Colon cancer cells via raising miR-622

Zhang

Lan

2019

Artificial Cells, Nanomedicine, and Biotechnology

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“…Activation of this pathway results in the phosphorylation of transcription factors, which increases the expression of anti-apoptotic members and decreases the levels of pro-apoptotic proteins in the Bcl-2 family, subsequently inhibiting the release of cytochrome c from the mitochondria, and activating the apoptotic caspase cascade (47). The MAPK/ERK signaling pathway is associated with the cell proliferation and apoptosis, and cross-talk between the PI3K/AKT and MAPK/ERK pathways exists in numerous cancer cells (54)(55)(56). PI3K/AKT signaling pathway abrogation may lead to a compensatory activation of the MAPK/ERK signaling pathway (57).…”

Section: Discussionmentioning

confidence: 99%

Curcumin attenuates resistance to irinotecan via induction of apoptosis of cancer stem cells in chemoresistant colon cancer cells

Yang

Wang

et al. 2018

Int J Oncol

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Resistance to conventional chemotherapeutic agents, including irinotecan (CPT‑11), 5-fluorouracil and capecitabine is a major cause for therapeutic failure in patients with colorectal cancer (CRC). Increasing evidence has demonstrated that cancer cells exhibiting stem cell-like characteristics are associated with the development of resistance to chemotherapeutic agents. As a plant polyphenol, curcumin has been demonstrated to have the ability to ameliorate resistance of CRC to chemotherapeutic agents, but the associations among curcumin, cancer stem cells (CSCs) and chemoresistance of CRC remain unclear. The present study established a CPT‑11-resistant colon cancer cell line, LoVo/CPT‑11 cells, and detected the expression levels of CSC identification markers [cluster of differentiation (CD)44, CD133, epithelial cell adhesion molecule (EpCAM) and CD24] in parental cells and CPT‑11-resistant cells. It was revealed that the expression levels of the colon CSC markers in LoVo/CPT‑11 cells were significantly higher compared those in parental cells at the mRNA and protein level. The effect of curcumin on the chemoresistance to CPT‑11 and the expression levels of CSC identification markers in LoVo/CPT‑11 cells separately treated with curcumin and CPT‑11 were further investigated. The results revealed that curcumin significantly attenuated chemoresistance to CPT‑11, and treatment with curcumin resulted in a significant reduction of the expression levels of CSC identification markers. Furthermore, a tumor sphere formation assay was used to enrich colon CSCs from LoVo/CPT‑11 cells, and demonstrated that curcumin efficiently diminished the traits of colon CSCs, as evidenced by the inability to form tumor spheres, the reduction in the expression of CSC identification markers, and apoptosis-induced effects on sphere-forming cells treated with curcumin alone or in combination with CPT‑11. Altogether, the present data demonstrated that curcumin attenuated resistance to chemotherapeutic drugs through induction of apoptosis of CSCs among colon cancer cells. These findings may provide novel evidence for the therapeutic application of curcumin in CRC intervention.

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“…Carrots are the main source of carotenoids, and previous studies have demonstrated that carrots may reduce cancer risk and play an important role in a cancer prevention diet [ 40 , 41 , 42 ]. Carrots are traditionally used for the treatment of gastric ulcers, diabetes, muscle pain and cancer in Lebanon [ 43 ]. Carrots have been reported to provide numerous biological activities, including antibacterial, antifungal, diuretic, antilithic, anticancer, antiinflammatory and antioxidant effects [ 43 , 44 , 45 , 46 , 47 ].…”

Section: Discussionmentioning

confidence: 99%

“…Carrots are traditionally used for the treatment of gastric ulcers, diabetes, muscle pain and cancer in Lebanon [ 43 ]. Carrots have been reported to provide numerous biological activities, including antibacterial, antifungal, diuretic, antilithic, anticancer, antiinflammatory and antioxidant effects [ 43 , 44 , 45 , 46 , 47 ]. In this study, we purified a BCSC inhibitor from carrots ( Figure 1 ) and identified as 6-methoxymellein by electrospray ionization (ESI)-MS and NMR spectroscopy ( Figure 2 ).…”

Section: Discussionmentioning

confidence: 99%

6-Methoxymellein Isolated from Carrot (Daucus carota L.) Targets Breast Cancer Stem Cells by Regulating NF-κB Signaling

et al. 2020

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The presence of breast cancer stem cells (BCSCs) induces the aggressive progression and recurrence of breast cancer. These cells are drug resistant, have the capacity to self-renew and differentiate and are involved in recurrence and metastasis, suggesting that targeting BCSCs may improve treatment efficacy. In this report, methanol extracts of carrot root were purified by means of silica gel, Sephadex LH-20, and preparative high-performance liquid chromatography to isolate a compound targeting mammosphere formation. We isolated the compound 6-methoxymellein, which inhibits the proliferation and migration of breast cancer cells, reduces mammosphere growth, decreases the proportion of CD44+/CD24− cells in breast cancer cells and decreases the expression of stemness-associated proteins c-Myc, Sox-2 and Oct4. 6-Methoxymellein reduces the nuclear localization of nuclear factor-κB (NF-κB) subunit p65 and p50. Subsequently, 6-methoxymellein decreases the mRNA transcription and secretion of IL-6 and IL-8. Our data suggest that 6-methoxymellein may be an anticancer agent that inhibits BCSCs via NF-κB/IL-6 and IL-8 regulation.

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Antitumor activity of β-2-himachalen-6-ol in colon cancer is mediated through its inhibition of the PI3K and MAPK pathways

Cited by 28 publications

References 28 publications

RETRACTED ARTICLE: Silencing UNC5B antisense lncRNA 1 represses growth and metastasis of human Colon cancer cells via raising miR-622

RETRACTED ARTICLE: Silencing UNC5B antisense lncRNA 1 represses growth and metastasis of human Colon cancer cells via raising miR-622

Curcumin attenuates resistance to irinotecan via induction of apoptosis of cancer stem cells in chemoresistant colon cancer cells

6-Methoxymellein Isolated from Carrot (Daucus carota L.) Targets Breast Cancer Stem Cells by Regulating NF-κB Signaling

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