Curcumin co-treatment ameliorates resistance to gefitinib in drug-resistant NCI-H1975 lung cancer cells

Jin, Xin; Wang, Jue; Huifen, Shen; Ran, Ran; Xu, Kan; Tong, Xiangming; Zhang, Weiping; Li, Feng

doi:10.1016/s0254-6272(17)30071-7

Cited by 12 publications

(6 citation statements)

References 13 publications

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“…The extracellular signal-regulated kinase (ERK) pathway is crucial for cancer cell chemosensitivity [38]. CU affects the ERK 1/2 pathway specifically, resulting in a 75% decrease in its expression [39]. In this study, CU17 inhibited the growth of lung cancer A549 cells through the same underlying mechanism as CU (Figures 5-8).…”

Section: Discussionmentioning

confidence: 55%

HDAC Inhibitory and Anti-Cancer Activities of Curcumin and Curcumin Derivative CU17 against Human Lung Cancer A549 Cells

et al. 2022

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Previous research reported that the curcumin derivative (CU17) inhibited several cancer cell growths in vitro. However, its anticancer potential against human lung cancer cells (A549 cell lines) has not yet been evaluated. The purpose of this research was to examine the HDAC inhibitory and anti-cancer activities of CU17 compared to curcumin (CU) in A549 cells. An in vitro study showed that CU17 had greater HDAC inhibitory activity than CU. CU17 inhibited HDAC activity in a dose dependent manner with the half-maximal inhibitory concentration (IC50) value of 0.30 ± 0.086 µg/mL against HDAC enzymes from HeLa nuclear extract. In addition, CU17 could bind at the active pockets of both human class I HDACs (HDAC1, 2, 3, and 8) and class II HDACs (HDAC4, 6, and 7) demonstrated by molecular docking studies, and caused hyperacetylation of histone H3 (Ac-H3) in A549 cells shown by Western blot analysis. MTT assay indicated that both CU and CU17 suppressed A549 cell growth in a dose- and time-dependent manner. Besides, CU and CU17 induced G2/M phase cell cycle arrest and p53-independent apoptosis in A549 cells. Both CU and CU17 down-regulated the expression of p53, p21, Bcl-2, and pERK1/2, but up-regulated Bax expression in this cell line. Although CU17 inhibited the growth of lung cancer cells less effectively than CU, it showed less toxicity than CU for non-cancer cells. Accordingly, CU17 is a promising agent for lung cancer treatment. Additionally, CU17 synergized the antiproliferative activity of Gem in A549 cells, indicating the possibility of employing CU17 as an adjuvant treatment to enhance the chemotherapeutic effect of Gem in lung cancer.

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Section: Discussionmentioning

confidence: 55%

HDAC Inhibitory and Anti-Cancer Activities of Curcumin and Curcumin Derivative CU17 against Human Lung Cancer A549 Cells

et al. 2022

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“…Side effects of gefitinib like villi damage and gastrointestinal effects were also attenuated by curcumin ( Lee et al, 2011 ). Several other curcumin and gefitinib combination studies also found that curcumin promotes the inhibitory activity of gefitinib through downregulation of EGFR, MAPK, and PI3K signaling pathways ( Lee et al, 2007 ; Xin et al, 2017 ; Chen et al, 2019 ). It was further found that curcumin and gefitinib also suppressed Sp1-and HDAC-induced EGFR transcription which led to induction of autophagy ( Chen et al, 2019 ).…”

Section: Curcumin-receptor Tyrosine Kinase Inhibitor Combinationmentioning

confidence: 98%

Receptor Tyrosine Kinases and Their Signaling Pathways as Therapeutic Targets of Curcumin in Cancer

et al. 2021

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Receptor tyrosine kinases (RTKs) are transmembrane cell-surface proteins that act as signal transducers. They regulate essential cellular processes like proliferation, apoptosis, differentiation and metabolism. RTK alteration occurs in a broad spectrum of cancers, emphasising its crucial role in cancer progression and as a suitable therapeutic target. The use of small molecule RTK inhibitors however, has been crippled by the emergence of resistance, highlighting the need for a pleiotropic anti-cancer agent that can replace or be used in combination with existing pharmacological agents to enhance treatment efficacy. Curcumin is an attractive therapeutic agent mainly due to its potent anti-cancer effects, extensive range of targets and minimal toxicity. Out of the numerous documented targets of curcumin, RTKs appear to be one of the main nodes of curcumin-mediated inhibition. Many studies have found that curcumin influences RTK activation and their downstream signaling pathways resulting in increased apoptosis, decreased proliferation and decreased migration in cancer both in vitro and in vivo. This review focused on how curcumin exhibits anti-cancer effects through inhibition of RTKs and downstream signaling pathways like the MAPK, PI3K/Akt, JAK/STAT, and NF-κB pathways. Combination studies of curcumin and RTK inhibitors were also analysed with emphasis on their common molecular targets.

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“…Chemoresistance towards this treatment is becoming more prevalent, where the abnormal amplification of EGFR was massively identified in NSCLC patients [ 157 ]. Flow cytometric apoptotic analysis revealed that the co-treatment of curcumin (10 ng/mL) and gefitinib (0.1 mol/L) significantly augmented the apoptosis in NCI-H1975 lung cancer cells by blocking EGFR signalling pathways, notably Akt and ERK1/2 phosphorylation [ 93 ]. Apart from enhancing apoptosis, the co-treatment of curcumin and gefitinib induced autophagy-related cell death, which was associated with the suppression of histone deacetylase activities and the proteasomal degradation of EGFR proteins.…”

Section: Curcumin Combination Anticancer Therapy In Preclinical Studiesmentioning

confidence: 99%

Is Curcumin the Answer to Future Chemotherapy Cocktail?

et al. 2021

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The rise in cancer cases in recent years is an alarming situation worldwide. Despite the tremendous research and invention of new cancer therapies, the clinical outcomes are not always reassuring. Cancer cells could develop several evasive mechanisms for their survivability and render therapeutic failure. The continuous use of conventional cancer therapies leads to chemoresistance, and a higher dose of treatment results in even greater toxicities among cancer patients. Therefore, the search for an alternative treatment modality is crucial to break this viscous cycle. This paper explores the suitability of curcumin combination treatment with other cancer therapies to curb cancer growth. We provide a critical insight to the mechanisms of action of curcumin, its role in combination therapy in various cancers, along with the molecular targets involved. Curcumin combination treatments were found to enhance anticancer effects, mediated by the multitargeting of several signalling pathways by curcumin and the co-administered cancer therapies. The preclinical and clinical evidence in curcumin combination therapy is critically analysed, and the future research direction of curcumin combination therapy is discussed.

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Curcumin co-treatment ameliorates resistance to gefitinib in drug-resistant NCI-H1975 lung cancer cells

Cited by 12 publications

References 13 publications

HDAC Inhibitory and Anti-Cancer Activities of Curcumin and Curcumin Derivative CU17 against Human Lung Cancer A549 Cells

HDAC Inhibitory and Anti-Cancer Activities of Curcumin and Curcumin Derivative CU17 against Human Lung Cancer A549 Cells

Receptor Tyrosine Kinases and Their Signaling Pathways as Therapeutic Targets of Curcumin in Cancer

Is Curcumin the Answer to Future Chemotherapy Cocktail?

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