Genistein promotes ionizing radiation-induced cell death by reducing cytoplasmic Bcl-xL levels in non-small cell lung cancer

Zhang, Zhimin; Jin, Feng; Lian, Xin; Li, Mengxia; Wang, Ge; Lan, Baohua; He, Hao; Liu, Guodong; Wu, Yan; Sun, Guan; Xu, Cheng-Xiong; Yang, Zhenzhou

doi:10.1038/s41598-017-18755-3

Cited by 35 publications

(25 citation statements)

References 30 publications

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“…The Bcl-xL pathway inhibition has been demonstrated to improve the resistance to radiotherapy in lung cancer patients [100]. Genistein treatment increased the radiosensitivity of lung cancer cells through stimulating apoptosis due to the reducing plasmic Bcl-xL levels [101]. Baicalein increased the sensitivity of cisplatin in lung cancer cells via the PI3K/Akt/NFκB pathway mediated-EMT [102].…”

Section: Flavonoids In Combination With Chemotherapeutic and Radiomentioning

confidence: 99%

Progress in Research on the Role of Flavonoids in Lung Cancer

Zănoagă

Braicu

Jurj

et al. 2019

IJMS

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Lung cancer is the leading cause of cancer deaths worldwide. Therefore, for the prevention, diagnosis, prognosis and treatment of lung cancer, efficient preventive strategies and new therapeutic strategies are needed to face these challenges. Natural bioactive compounds and particular flavonoids compounds have been proven to have an important role in lung cancer prevention and of particular interest is the dose used for these studies, to underline the molecular effects and mechanisms at a physiological concentration. The purpose of this review was to summarize the current state of knowledge regarding relevant molecular mechanisms involved in the pharmacological effects, with a special focus on the anti-cancer role, by regulating the coding and non-coding genes. Furthermore, this review focused on the most commonly altered and most clinically relevant oncogenes and tumor suppressor genes and microRNAs in lung cancer. Particular attention was given to the biological effect in tandem with conventional therapy, emphasizing the role in the regulation of drug resistance related mechanisms.

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Section: Flavonoids In Combination With Chemotherapeutic and Radiomentioning

confidence: 99%

Progress in Research on the Role of Flavonoids in Lung Cancer

Zănoagă

Braicu

Jurj

et al. 2019

IJMS

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“…Furthermore, Bcl-x was also involved in the regulation of autophagy through the molecular interaction with the Beclin-1 protein [160,161]. Summarizing, the authors suggest that the Genistein has a potential radiosensitizing effect in the NSCLC cells, because able to regulate the Bcl-x cytoplasmic expression level and thus apoptotic and autophagic processes [162].…”

Section: Genisteinmentioning

confidence: 99%

Nutraceutical Compounds as Sensitizers for Cancer Treatment in Radiation Therapy

Calvaruso

Pucci

Musso

et al. 2019

IJMS

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The improvement of diagnostic techniques and the efficacy of new therapies in clinical practice have allowed cancer patients to reach a higher chance to be cured together with a better quality of life. However, tumors still represent the second leading cause of death worldwide. On the contrary, chemotherapy and radiotherapy (RT) still lack treatment plans which take into account the biological features of tumors and depend on this for their response to treatment. Tumor cells’ response to RT is strictly-connected to their radiosensitivity, namely, their ability to resist and to overcome cell damage induced by ionizing radiation (IR). For this reason, radiobiological research is focusing on the ability of chemical compounds to radiosensitize cancer cells so to make them more responsive to IR. In recent years, the interests of researchers have been focused on natural compounds that show antitumoral effects with limited collateral issues. Moreover, nutraceuticals are easy to recover and are thus less expensive. On these bases, several scientific projects have aimed to test also their ability to induce tumor radiosensitization both in vitro and in vivo. The goal of this review is to describe what is known about the role of nutraceuticals in radiotherapy, their use and their potential application.

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“…Finally, slides were incubated with 3,30‐diaminobenzidine (DAB) substrate. Scoring for cytoplasmic APE1 staining was performed as described previously by three professional pathologists …”

Section: Methodsmentioning

confidence: 99%

Cytoplasmic APE1 promotes resistance response in osteosarcoma patients with cisplatin treatment

Liu

Zhang

et al. 2020

Cell Biochemistry & Function

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Chemotherapy resistance has become a hold back and major clinical challenge in osteosarcoma cancer. The alteration and subcellular distribution of apurinic/ apyrimidinic endonuclease 1 (APE1) has been reported to be involved in chemotherapy resistance in many cancers. Here, we report that the cytoplasmic distribution of APE1 plays a key role in the sensitivity of combination platinum chemotherapy in osteosarcoma. Interestingly, the prevalence of cisplatin-induced DNA damage and apoptosis in low cytoplasmic APE1 osteosarcoma cell lines was higher than in high expression of cytoplasmic APE1 cell lines. Overexpression of cytoplasmic APE1 protected the osteosarcoma cells from CDDP-induced apoptosis. In addition, clinical data also show that the level of cytoplasmic APE1 was negatively associated with sensitivity to combination chemotherapy of cisplatin in osteosarcoma patients. Our findings suggest that cytoplasmic APE1 plays a significant role in chemotherapy resistance. This role is a supplement to the extranuclear function of APE1, and cytoplasmic APE1 expression level could be a promising predictor of platinum treatment prognosis for osteosarcoma patients. K E Y W O R D S APE1, cisplatin resistance, cytoplasmic, predictor 1 | INTRODUCTION Osteosarcoma has become the most common primary malignant bone tumor, mainly in adolescent and young patients. 1,2 Cisplatin is one of the traditional chemotherapeutic agents used for osteosarcoma treatment. The mechanism of toxicity cisplatin is crosslinking DNA and formed DNA-cisplatin adducts, which in turn induce DNA damage. 3 Platinum-based drugs are the standard first-line agents used alone or in combination with other drugs for osteosarcoma treatment. 4,5 However, the present protocols seem to have reached a plateau, 6 which may be associated with chemotherapy resistance. The molecular mechanisms of cisplatin resistance are complex and usually associated with a reduction in the intracellular accumulation of the platinum compounds and an increase in DNA damage repair. 3 Chemotherapy resistance has been linked with poor prognosis. Human apurinic/apyrimidinic endonuclease 1 (APE1/Ref-1) is a multifunctional protein that has both DNA damage repair and redox functions. As an essential enzyme in DNA base excision repair (BER), APE1 is involved in repairing DNA damage, creating an abasic site (apurinic/apyrimidinic, AP site) caused by oxidizers and alkylating agents. 7 APE1 is the key regulator in the cellular oxidative stress pathway, which maintains the activity of numerous cellular transcription factors, such as AP-1, NF-κB, Myb, HIF-1α, HLF, PAX, and p53, through keeping specific cysteine residues in the DNA binding domain reduced state. Moreover, some of these transcription factors are closely related to chemotherapy resistance. 8-10List of Abbreviations: AMLs, acute myeloid leukemias; Ang II, angiotensin II; AP sites, apurinic/apyrimidinic sites; AP-1, activator protein 1; APE1, apurinic/apyrimidinic endonuclease; BER, base excision repair; GADD45α, DNA damage-inducible pr...

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Genistein promotes ionizing radiation-induced cell death by reducing cytoplasmic Bcl-xL levels in non-small cell lung cancer

Cited by 35 publications

References 30 publications

Progress in Research on the Role of Flavonoids in Lung Cancer

Progress in Research on the Role of Flavonoids in Lung Cancer

Nutraceutical Compounds as Sensitizers for Cancer Treatment in Radiation Therapy

Cytoplasmic APE1 promotes resistance response in osteosarcoma patients with cisplatin treatment

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