Capsaicin enhances erlotinib-induced cytotoxicity <i>via</i> AKT inactivation and excision repair cross-complementary 1 (ERCC1) down-regulation in human lung cancer cells

Chen, Jyh-Cheng; Ko, Jen-Chung; Yen, Ting-Chuan; Chen, Tzu‐Ying; Lin, Yuan-Cheng; Ma, Peng-Fang

doi:10.1039/c8tx00346g

Cited by 18 publications

(10 citation statements)

References 47 publications

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“…Ferulic acid potentiated the effects of PARP inhibitors on breast cancer cells by reducing the formation of RAD51 foci and lengthening the time that double-stranded DNA breaks remain unrepaired (110). Capsaicin, the main bioactive compound found in chili peppers of the Capsicum genus, downregulates the ERCC1 protein in lung cancer cells by promoting its proteasomal degradation, thereby enhancing the cytotoxic effects of the EGFR inhibitor erlotinib (111,112). b-Thujaplicin, a natural monoterpenoid found in the wood of trees in the Cupressaceae family, sensitized osteosarcoma cells to damage caused by ionizing radiation, as it inhibits the formation of RAD51 foci and keeps RPA phosphorylated (113).…”

Section: Other Compoundsmentioning

confidence: 99%

Natural Compounds That Target DNA Repair Pathways and Their Therapeutic Potential to Counteract Cancer Cells

Lagunas‐Rangel

Bermúdez‐Cruz

2020

Front. Oncol.

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Resistance to current cancer treatments is an important problem that arises through various mechanisms, but one that stands out involves an overexpression of several factors associated with DNA repair. To counteract this type of resistance, different drugs have been developed to affect one or more DNA repair pathways, therefore, to test different compounds of natural origin that have been shown to induce cell death in cancer cells is paramount. Since natural compounds target components of the DNA repair pathways, they have been shown to promote cancer cells to be resensitized to current treatments. For this and other reasons, natural compounds have aroused great curiosity and several research projects are being developed around the world to establish combined treatments between them and radio or chemotherapy. In this work, we summarize the effects of different natural compounds on the DNA repair mechanisms of cancer cells and emphasize their possible application to re-sensitize these cells.

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Section: Other Compoundsmentioning

confidence: 99%

Natural Compounds That Target DNA Repair Pathways and Their Therapeutic Potential to Counteract Cancer Cells

Lagunas‐Rangel

Bermúdez‐Cruz

2020

Front. Oncol.

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“…It was reported that capsaicin significantly increased the apoptotic cell death of B‐lymphoma cells under the treatment of etoposide (Taylor, Hickman, & Dive, 2000). Besides, Chen et al revealed that the combination of capsaicin and erlotinib synergistically enhanced the cell growth inhibition of non‐small cell lung cancer cells (Chen et al, 2019). For radio‐sensitizing, the prostate tumor growth rate with oral administration of capsaicin and radiotherapy was reduced more than a single administration of each one (Venier et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Capsaicin inhibits the stemness of anaplastic thyroid carcinoma cells by triggering autophagy‐lysosome mediated OCT4A degradation

Cheng

et al. 2022

Phytotherapy Research

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Capsaicin (CAP) is a well‐known anti‐cancer agent. Recently, we reported capsaicin‐induced apoptosis in anaplastic thyroid cancer (ATC) cells. It is well accepted that the generation of cancer stem cells (CSCs) is responsible for the dedifferentiation of ATC, the most lethal subtype of thyroid cancer with highly dedifferentiation status. Whether CAP inhibited the ATC growth through targeting CSCs needed further investigation. In the present study, CAP was found to induce autophagy in ATC cells through TRPV1 activation and subsequent calcium influx. Meanwhile, CAP dose‐dependently decreased the sphere formation capacity of ATC cells. The stemness‐inhibitory effect of CAP was further by extreme limiting dilution analysis (ELDA). CAP significantly decreased the protein level of OCT4A in both 8505C and FRO cells. Furthermore, CAP‐induced OCT4A degradation was reversed by autophagy inhibitors 3‐MA and chloroquine, BAPTA‐AM and capsazepine, but not proteasome inhibitor MG132. Collectively, our study firstly showed CAP suppressed the stemness of ATC cells partially via calcium‐dependent autophagic degradation of OCT4A. Our study lent credence to the feasible application of capsaicin in limiting ATC stemness.

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“…Amid the effort to combat the resistance of EGFR-TKIs [24], combination treatment has been deemed the most promising approach to overcome the resistance problem [25]. Several studies have probed the effect of combining Erl and other anticancer agents such as cisplatin, monoclonal antibodies, aspirin, and capsaicin [10, 26–28], whose applications, however, have been hampered by unpredictable drug interactions or side effects so far. The study demonstrated for the first time the effect of the physical stimulation of TC-HT in boosting the anticancer effect of Erl, without hurting the normal lung cells, thereby sidestepping drug interaction problem and significantly reducing the needed dosage of Erl, which lessens side effects.…”

Section: Discussionmentioning

confidence: 99%

Thermal cycling hyperthermia sensitizes non-small cell lung cancer A549 cells to EGFR-tyrosine kinase inhibitor Erlotinib

Chen

Lin

Liu

et al. 2022

Preprint

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Molecular-targeted therapy has emerged as a mainstream treatment for non-small cell lung cancer (NSCLC), the most common lung cancer, which has been the leading cause of cancer death for both men and women. Erlotinib (Erl), a targeted therapy drug which triggers epidermal growth factor receptor (EGFR) pathways, has been proved to have noticeable response rate for NSCLC cells. However, it has achieved only limited treatment effect, due to intrinsic and acquired resistance among most NSCLC patients. Therefore, chemosensitizers are required to potentiate the efficacy of Erl in NSCLC treatment. The study proposed a novel thermal therapy, thermal cycling hyperthermia (TC-HT), as a supplement to amplify the effect of Erl, and proved that it can sensitize A549 NSCLC cells to Erl via the downstream of EGFR signaling cascades. In addition, we found that TC-HT not only greatly enhanced the anticancer effect of Erl but also remarkably reduced the half-maximal inhibitory concentration (IC50) to as little as 0.5 μM. Besides, via regulation of thermal dosage, TC-HT alone can produce excellent antineoplastic effect without hurting the normal cells. The method is expected to be applicable to other combination therapies and may be a starter for more sophisticated, side-effect-free anticancer treatments.

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Capsaicin enhances erlotinib-induced cytotoxicity via AKT inactivation and excision repair cross-complementary 1 (ERCC1) down-regulation in human lung cancer cells

Abstract: Capsaicin, a natural active ingredient of green and red peppers, has been demonstrated to exhibit anti-cancer properties in several malignant cell lines.

Cited by 18 publications

References 47 publications

Natural Compounds That Target DNA Repair Pathways and Their Therapeutic Potential to Counteract Cancer Cells

Natural Compounds That Target DNA Repair Pathways and Their Therapeutic Potential to Counteract Cancer Cells

Capsaicin inhibits the stemness of anaplastic thyroid carcinoma cells by triggering autophagy‐lysosome mediated OCT4A degradation

Thermal cycling hyperthermia sensitizes non-small cell lung cancer A549 cells to EGFR-tyrosine kinase inhibitor Erlotinib

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