<i>Retracted</i>: Icariin attenuates methotrexate chemotherapy‐induced bone marrow microvascular damage and bone loss in rats

Hassanshahi, Mohammadhossein; Y, Su; Khabbazi, Samira; Fan, Chiaming; Tang, Qian; Wen, Xiaopeng; Fan, Jie; Chen, Keming; Chen, Xian

doi:10.1002/jcp.28326

Cited by 7 publications

(4 citation statements)

References 49 publications

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“…Interestingly, Jiang et al demonstrated that icariin significantly enhanced the chemosensitivity of cisplatin-resistant ovarian cancer cells by suppressing autophagy [31]. Moreover, icariin could effectively attenuate paclitaxel-induced neuropathic pain [32] and chemotherapy-induced bone marrow microvascular damage [33]. Based on these evidences, we thus speculated that icariin might play an important role in TAM resistance.…”

Section: Introductionmentioning

confidence: 99%

Icariin induces apoptosis by suppressing autophagy in tamoxifen-resistant breast cancer cell line MCF-7/TAM

et al. 2019

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Background Icariin is a major component isolated from Epimedium brevicornum Maxim and has been reported to exhibit anti-tumor activity. However, whether icariin could reverse the acquired drug resistance in breast cancer remains largely unclear. Therefore, this study was designed to explore the antitumor effects of icariin and its underlying mechanisms in a tamoxifen-resistant breast cancer cell line MCF-7/TAM. Methods 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Lactate dehydrogenase (LDH) assay were performed to determine the effects of icariin on cell viability and cell death. Cell cycle progression and apoptosis were detected by flow cytometry analysis. Transmission electron microscopy (TEM) assay was utilized to observe cell autophagy. The downstream protein levels were measured using western blotting. Results Here, we observed that icariin treatment not only inhibited the growth of MCF-7 but also has a potential function to overcome tamoxifen resistance in MCF-7/TAM. Moreover, icariin significantly induced cell cycle G0/G1 phase arrest and apoptosis, as well as suppressed autophagy. At molecular levels, icariin treatment remarkably down-regulated the expression levels of CDK2, CDK4, Cyclin D1, Bcl-2, LC3-1, LC3-II, AGT5, Beclin-1, but upregulated the expression levels of caspase-3, PARP and p62. Most importantly, we found inhibition of autophagy via 3-MA treatment could significantly enhance the effects of icariin on cell viability and apoptosis. Enhanced autophagy via autophagy related 5 (ATG5) overexpression could partially reverse the effects of icariin on cell viability and apoptosis. Conclusion These results revealed that icariin might potentially be useful as an adjuvant agent in cancer chemotherapy to enhance the effect of tamoxifen through suppression of autophagy in vitro and provide insight into the therapeutic potential of icariin for the treatment of chemo-resistant breast cancer.

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Section: Introductionmentioning

confidence: 99%

Icariin induces apoptosis by suppressing autophagy in tamoxifen-resistant breast cancer cell line MCF-7/TAM

et al. 2019

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“…In addition, as CXCL12 exerts biological effects through binding with receptor CXCR4, future studies are required to further investigate the potential roles of CXCL12‐CXCR4 axis in MTX and/or DEX treatment‐associated growth plate cartilage resorption and thinning and the potential therapeutic effect with administration of a CXCR4 inhibitor as used in a rodent bone cancer‐induced bone lysis model (Diamond et al, 2009). Furthermore, while previous studies have demonstrated that cancer chemotherapy including MTX chemotherapy can cause significant damage to the bone marrow microvascular system accompanying the aggravated bone loss (Hassanshahi et al, 2017; Hassanshahi et al, 2019a; 2019b; 2019c), further studies are required to clarify any possible effects of MTX and DEX treatments on vasculogenesis and/or angiogenesis at the growth plate/metaphysis junction. This is important as vasculogenesis and/or angiogenesis are crucial for remodelling calcified hypertrophic growth plate cartilage into woven bone (primary spongiosa) and thus for the coupling of cartilage scaffold production and new endochondral bone formation during bone growth (Gerber et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Roles of apoptotic chondrocyte‐derived CXCL12 in the enhanced chondroclast recruitment following methotrexate and/or dexamethasone treatment

Fan

et al. 2021

Journal Cellular Physiology

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Intensive use of methotrexate (MTX) and/or dexamethasone (DEX) for treating childhood malignancies is known to cause chondrocyte apoptosis and growth plate dysfunction leading to bone growth impairments. However, mechanisms remain vague and it is unclear whether MTX and DEX combination treatment could have additive effects in the growth plate defects. In this study, significant cell apoptosis was induced in mature ATDC5 chondrocytes after treatment for 48 h with 10−5 M MTX and/or 10−6 M DEX treatment. PCR array assays with treated cells plus messenger RNA and protein expression confirmation analyses identified chemokine CXCL12 having the most prominent induction in each treatment group. Conditioned medium from treated chondrocytes stimulated migration of RAW264.7 osteoclast precursor cells and formation of osteoclasts, and these stimulating effects were inhibited by the neutralizing antibody for CXCL12. Additionally, while MTX and DEX combination treatment showed some additive effects on apoptosis induction, it did not have additive or counteractive effects on CXCL12 expression and its functions in enhancing osteoclastic recruitment and formation. In young rats treated acutely with MTX, there was increased expression of CXCL12 in the tibial growth plate, and more resorbing chondroclasts were found present at the border between the hypertrophic growth plate and metaphysis bone. Thus, the present study showed an association between induced chondrocyte apoptosis and stimulated osteoclastic migration and formation following MTX and/or DEX treatment, which could be potentially or at least partially linked molecularly by CXCL12 induction. This finding may contribute to an enhanced mechanistic understanding of bone growth impairments following MTX and/or DEX therapy.

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“…demonstrated that oral ICA treatment prevents bone loss in iron-overloaded mice and inhibited the differentiation and function of osteoclasts. In addition, ICA reduces bone loss induced by methotrexate chemotherapy in rats ( 23 ). As these studies demonstrate the osteoporosis-related activity of ICA, it was hypothesized that ICA may exert a protective effect on TAA-induced bone loss.…”

Section: Introductionmentioning

confidence: 99%

Icariin attenuates thioacetamide‑induced bone loss via the RANKL‑p38/ERK‑NFAT signaling pathway

et al. 2022

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There is an increasing incidence of destructive bone disease caused by osteoclast proliferation. This is characterized by reduced bone mass and imbalance of bone homeostasis. Icariin (ICA), a flavonoid compound isolated from Epimedium , has anti-osteoporosis activity and inhibits the formation of osteoclasts and bone resorption. The purpose of the present study was to investigate the protective effect of ICA on osteoclastic differentiation induced by thioacetamide (TAA) and its possible mechanism in Sprague Dawley (SD) rats. In the present study, SD rats were intraperitoneally injected with TAA (300 mg/kg) for the bone loss model, treated with ICA (600 mg/kg, intragastric gavage) in the ICA group and TAA+ICA group for treatment of bone loss for 6 weeks. Indexes associated with bone metabolism, such as alkaline phosphatase, N-terminal telopeptide of type-I collagen (NTX–I), calcium (Ca), phosphorus (P) and magnesium (Mg) in the serum, were detected. Osteoclast differentiation of femoral tissues was detected by hematoxylin and eosin and tartrate-resistant acid phosphatase staining. The femoral bone mass was evaluated using a three-point bending test and micro computed tomography. Western blotting was used to detect the expression levels of osteoclast-related proteins in each group. In the rats treated with TAA, the serum concentrations of Ca, P and Mg were decreased, the serum concentration of NTX–I was increased, osteoclast differentiation of the femur was increased, femur bone stress and bone mass were decreased and the bone loss and osteoclast formation were reduced after ICA treatment. In addition, ICA inhibited the protein expression of receptor activator of nuclear factor κ-Β ligand (RANKL), receptor activator of nuclear factor κ-B (RANK), p38, ERK, c-Fos and nuclear factor of activated T cells 1 (NFATc1) in the femur of rats treated with TAA. The results suggested that ICA may inhibit osteoclast differentiation by downregulating the RANKL-p38/ERK-NFAT signaling pathway and prevent TAA-induced bone loss. The results are helpful to understand the mechanism of osteoclast differentiation induced by TAA, as well as the antiresorptive activity and molecular mechanism of ICA, and to provide new ideas for the treatment of osteolytic diseases.

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Retracted: Icariin attenuates methotrexate chemotherapy‐induced bone marrow microvascular damage and bone loss in rats

Cited by 7 publications

References 49 publications

Icariin induces apoptosis by suppressing autophagy in tamoxifen-resistant breast cancer cell line MCF-7/TAM

Icariin induces apoptosis by suppressing autophagy in tamoxifen-resistant breast cancer cell line MCF-7/TAM

Roles of apoptotic chondrocyte‐derived CXCL12 in the enhanced chondroclast recruitment following methotrexate and/or dexamethasone treatment

Icariin attenuates thioacetamide‑induced bone loss via the RANKL‑p38/ERK‑NFAT signaling pathway

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