Hesperetin and Naringenin sensitize HER2 positive cancer cells to death by serving as HER2 Tyrosine Kinase inhibitors

Chandrika, Bhavya Balan; Steephan, Mathew; Kumar, T. R. Santhosh; Sabu, A.; Haridas, M.

doi:10.1016/j.lfs.2016.07.007

Cited by 76 publications

(51 citation statements)

References 51 publications

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“…Pretreatment of NAC prevented hesperetin-induced apoptosis, which is under control of ASK1/JNK pathway. In addition, hesperetin also induced apoptosis in triple-negative breast cancer MDA-MB-231 cells via intrinsic apoptotic pathway [53,[61][62][63][64]. In the light of previous findings, both naringenin and hesperetin are known as promising therapeutic candidates in breast cancer due to their sensitizing effect of HER2-positive breast cancer cells.…”

Section: Flavanonesmentioning

confidence: 59%

“…According to in vitro studies, it was shown that naringenin modulated NF-κB to induce apoptosis in the cells. Naringenin was effective in MCF-7 ERα+/ERβ + cell line, but not in ER-independent SKBR-3 (ERα−/ERβ−) cell line [52][53][54][55]. Thymus vulgaris ethanol extraction originated in naringenin induced cell cycle arrest at S and G2/M phases, which led to apoptotic induction in HTB26 and HTB132 breast cancer cells [52].…”

Section: Flavanonesmentioning

confidence: 98%

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Breast Cancer and Flavonoids as Treatment Strategy

Yerlikaya¹,

Arısan²,

Gürkan³

et al. 2017

Breast Cancer - From Biology to Medicine

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Breast cancer is the most prevalent cancer type among women. Despite recent progress in early detection and therapeutic strategies, the rate of mortality is increasing. Antiestrogens or aromatase inhibitors are preferred to treat the women diagnosed with estrogen-receptor (ER) positive tumors. However, breast tumors usually show intra-tumoral heterogeneity with ER-positive and-negative cells. The advanced breast cancer cells lose the estrogen responsiveness and become aggressive by developing new strategies for rapid proliferation such as mutations in cell cycle machinery. New promising drugs are still being investigating against these types of tumors especially to overcome acquired resistance against chemotherapeutic drugs; however, a successful treatment for metastatic tumors is still unclear. Flavonoids, with various pharmacological activities, are plant or fungus secondary metabolites present in human diet. In plants, beside their role in pigmentation, they may also act as messengers, regulators and cell cycle inhibitors. Therefore, they are being tested in ovarian, cervical as well as breast cancer. Due to the positive correlation between flavonoids-rich diet and lower risk of cancer, flavonoids are referred as chemopreventive agents. The current chapter emphasizes the therapeutic potential of flavonoids and their synthetic analogues as anti-cancer agents in breast cancer providing new insights into the molecular mechanisms.

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Section: Flavanonesmentioning

confidence: 59%

Section: Flavanonesmentioning

confidence: 98%

Breast Cancer and Flavonoids as Treatment Strategy

Yerlikaya¹,

Arısan²,

Gürkan³

et al. 2017

Breast Cancer - From Biology to Medicine

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show abstract

“…Paclitaxel is the most successful natural anti-cancer drug, which was extracted first from the bark and wood of Pacific Yew tree (98). Hesperetin (HP) and naringenin (NG) belong to flavonoids, which have shown anti-cancer and pro-apoptotic activity (99). An anthraquinone compound, aloe-emodin (AE), effectively suppressed HER2 expression and cell proliferation in a dose-dependent manner consistent with promotion of apoptosis and G1 cell cycle arrest in HER2 + BC cells.…”

Section: Targeted Delivery Drugsmentioning

confidence: 99%

Novel treatment strategies for patients with HER2‑positive breast cancer who do not benefit from current targeted therapy drugs (Review)

et al. 2018

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Abstract.Human epidermal growth factor receptor-2 positive breast cancer (HER2 + BC) is characterized by a high rate of metastasis and drug resistance. The advent of targeted therapy drugs greatly improves the prognosis of HER2 + BC patients. However, drug resistance or severe side effects have limited the application of targeted therapy drugs. To achieve more effective treatment, considerable research has concentrated on strategies to overcome drug resistance. Abemaciclib (CDK4/6 inhibitor), a new antibody-drug conjugate (ADC), src homology 2 (SH2) containing tyrosine phosphatase-1 (SHP-1) and fatty acid synthase (FASN) have been demonstrated to improve drug resistance. In addition, using an effective vector to accurately deliver drugs to tumors has shown good application prospects. Many studies have also found that natural anti-cancer substances produced effective results during in vitro and in vivo anti-HER2 + BC research. This review aimed to summarize the current status of potential clinical drugs that may benefit HER2 + BC patients in the future.

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“…Following treatment with high-concentration quercetin alone or in combination with tamoxifen, the Bcl-2 was downregulated while p21, p53, and Bax were upregulated, and the Bax/Bcl-2 was also increased. Oppositely, lower-concentration quercetin downregulated the expression levels of p21, p53, and Bax to some extent, accounting for 22.03 ± 0.61%,16.85 ± 3.78%, and 61.45 ± 1.37%, respectively. In addition, the Bcl-2 was slightly decreased though no significance was investigated in the expression of p21, p53, and Bax when cells were combined treatment with lower-concentration quercetin and tamoxifen.…”

mentioning

confidence: 97%

“…23 Other than ER-positive breast cancers, naringenin also acted as a tyrosine kinase inhibitor, thereby sensitizing ER-negative SKBR3 to death. 16 Despite showing antitumor effects on breast cancer, naringenin seemed not effective as it killed cells weakly. 24 Therefore, finding certain flavonoids that induce significant cell antiproliferative effects is extremely urgent.…”

mentioning

confidence: 99%

Quercetin exerts bidirectional regulation effects on the efficacy of tamoxifen in estrogen receptor‐positive breast cancer therapy: An in vitro study

Zhao

Zheng

et al. 2020

Environmental Toxicology

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Tamoxifen was widely applied in the therapy of estrogen receptor (ER)-positive breast cancer. With the purpose of determining the potential impacts of quercetin on its effectiveness, MCF-7 cells were selected as the in vitro model and several cellular biological behaviors (ie, cell proliferation, migration, invasion, cycle, apoptosis, and oxidative stress) were investigated. As results, quercetin showed contrasting doseresponse to cellular behaviors dependent on the ROS-regulated p53 signaling pathways. In detail, quercetin promoted cell proliferation and inhibited cell apoptosis at low concentrations, whereas high-concentration resulted in apoptosis induction. Moreover, quercetin at a low concentration significantly inhibited tamoxifen-induced antiproliferation in MCF-7 cells, whereas high concentrations enhanced cell apoptosis in a synergetic manner. The real-time quantitative polymerase chain reaction analysis further implied that quercetin exerted its dual roles in tamoxifen-induced antiproliferative effects by regulated the gene expression involved in cell metastasis, cycle, and apoptosis through the ER pathways. Our present study provides a considerable support to the combination of quercetin and tamoxifen on human ER-positive breast carcinoma management.

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Hesperetin and Naringenin sensitize HER2 positive cancer cells to death by serving as HER2 Tyrosine Kinase inhibitors

Cited by 76 publications

References 51 publications

Breast Cancer and Flavonoids as Treatment Strategy

Breast Cancer and Flavonoids as Treatment Strategy

Novel treatment strategies for patients with HER2‑positive breast cancer who do not benefit from current targeted therapy drugs (Review)

Quercetin exerts bidirectional regulation effects on the efficacy of tamoxifen in estrogen receptor‐positive breast cancer therapy: An in vitro study

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