16-Hydroxycleroda-3,13-dien-15,16-olide and N-Methyl-Actinodaphine Potentiate Tamoxifen-Induced Cell Death in Breast Cancer

Velmurugan, Bharath Kumar; Wang, Po-Chih; Weng, Ching‐Feng

doi:10.3390/molecules23081966

Cited by 8 publications

(7 citation statements)

References 27 publications

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“…Moreover, the results of the experiments with the ERα-negative MDA-MB-231 breast cancer cells revealed the marked suppression of cell growth and activation of apoptotic cell death under co-treatment with metformin and tamoxifen; moreover, even tamoxifen alone induced non-remarkable cell death supporting the existence of ERα-independent ways of tamoxifen action. Importantly, the tamoxifen ability to inhibit the growth of ERα-negative and/or resistant breast cancer cells was found in several observations [ 27 , 44 , 45 , 46 , 47 , 48 ]. We suggest that ERα-independent tamoxifen action may be realized via the suppression of growth-related or antiapoptotic transcription factors.…”

Section: Discussionmentioning

confidence: 99%

Metformin Restores the Drug Sensitivity of MCF-7 Cells Resistant Derivates via the Cooperative Modulation of Growth and Apoptotic-Related Pathways

et al. 2020

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The phenomenon of the primary or acquired resistance of cancer cells to antitumor drugs is among the key problems of oncology. For breast cancer, the phenomenon of the resistance to hormonal or target therapy may be based on the numerous mechanisms including the loss or mutation of estrogen receptor, alterations of antiapoptotic pathways, overexpression of growth-related signaling proteins, etc. The perspective approaches for overcoming the resistance may be based on the usage of compounds such as inhibitors of the cell energetic metabolism. Among the latter, the antidiabetic drug metformin exerts antitumor activity via the activation of AMPK and the subsequent inhibition of mTOR signaling. The experiments were performed on the ERα-positive MCF-7 breast cancer cells, the MCF-7 sublines resistant to tamoxifen (MCF-7/T) and rapamycin (MCF-7/Rap), and on triple-negative MDA-MB-231 breast cancer cells. We have demonstrated metformin’s ability to enhance the cytostatic activity of the tamoxifen and rapamycin on both parent MCF-7 cells and MCF-7-resistant derivates mediated via the suppression of mTOR signaling and growth-related transcriptional factors. The cooperative effect of metformin and tested drugs was realized in an estrogen-independent manner, and, in the case of tamoxifen, was associated with the activation of apoptotic cell death. Similarly, the stimulation of apoptosis under metformin/tamoxifen co-treatment was shown to occur in the MCF-7 cells after steroid depletion as well as in the ERα-negative MDA-MB-231 cells. We conclude that metformin co-treatment may be used for the increase and partial restoration of the cancer cell sensitivity to hormonal and target drugs. Moreover, the combination of metformin with tamoxifen induces the apoptotic death in the ERα-negative breast cancer cells opening the additional perspectives in the treatment of estrogen-independent breast tumors.

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Section: Discussionmentioning

confidence: 99%

Metformin Restores the Drug Sensitivity of MCF-7 Cells Resistant Derivates via the Cooperative Modulation of Growth and Apoptotic-Related Pathways

et al. 2020

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“…For breast cancer, HCD potentiates tamoxifen-induced cell death in both ER-positive and -negative breast cells via enhancing extracellular apoptotic signaling 35 . In the present study is the rst report about treating e cacy of HCD in Dox-S and Dox-R of NSCLC cells.…”

Section: Discussionmentioning

confidence: 99%

Diterpene 16-hydroxycleroda-3,13-dien-15,16-olide emerges non-canonical autophagic cell death in doxorubicin-resistant lung cancer

Chiu¹,

Shen²,

Wu³

et al. 2020

Preprint

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Background: The antitumor activity of HCD has been reported in numerous types of cancers. Moreover, the antitumor of HCD could also be applied in non-small-cell lung cancer (NSCLC) cells and further act on doxorubicin-resistant (Dox-R) of NSCLC cells. The underlying anti-cancer mechanism of HCD on Dox-R versus Dox-sensitive (Dox-S) of A549 cells was under this investigation. Methods: Cytotoxicity of HCD against two cell lines (Dox-S and Dox-R) were determined via MTT assay, flow cytometry, and Western blot; and further examination of its anti-cancer efficacy in A549-bearing xenograft mice via orthotopic intratrachea (IT) inoculation. Result: Regardless sensitive and resistant to Dox, HCD could arrest both Dox-S and Dox-R cells at G 2 /M phase without altering the sub-G 1 cycle along with increasing cleaved-PARP. HCD downregulated the mTOR/Akt/PI3K-p85 and PI 3 K-ClassIII/Beclin-1 and upregulated p62/LC3-I/II expressions, further confirmed the cell autophagy after HCD-induced. Morphological observations of the mouse lung sections illustrated that fewer cancer cells accumulated around the trachea while there were less neoplastic activities found in HCD orthotopic treatment mice without liver, kidney and spleen toxicity. Conclusion: HCD exhibited the chemotherapeutic potential for lung cancer in Dox-resistant cells, suggesting natural autophagic inducer HCD provides a promising clue of new drug discovery and development for lung cancer therapy.

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“…For the antitumor effect, HCD could activate apoptotic cell death in chronic myelogenous leukemia cells [39], renal carcinoma cells [40], autophagic cell death in oral squamous cell carcinoma [41], and glioma cells via ROS burst [42]. For breast cancer treatment, HCD pretreatment could potentiate tamoxifen tumoricidal efficacy via down-regulating anti-apoptotic signaling [43]. In renal cell carcinoma cells, HCD induced anoikis by decreasing focal adhesion kinase-related signaling, which blocks tumor cell invasion and turns into apoptosis [44].…”

Section: Discussionmentioning

confidence: 99%

Polyalthia Clerodane Diterpene Potentiates Hypoglycemia via Inhibition of Dipeptidyl Peptidase 4

Huang

Lin

Riyaphan

et al. 2019

IJMS

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Serine protease dipeptidyl peptidase 4 (DPP-4) is involved in self/non-self-recognition and insulin sensitivity. DPP-4 inhibitors are conventional choices for diabetic treatment; however, side effects such as headache, bronchus infection, and nasopharyngitis might affect the daily lives of diabetic patients. Notably, natural compounds are believed to have a similar efficacy with lower adverse effects. This study aimed to validate the DPP-4 inhibitory activity of clerodane diterpene 16-hydroxycleroda-3,13-dien-15,16-olide (HCD) from Polyalthia longifolia, rutin, quercetin, and berberine, previously selected through molecular docking. The inhibitory potency of natural DPP-4 candidates was further determined by enzymatic, in vitro Caco-2, and ERK/PKA activation in myocyte and pancreatic cells. The hypoglycemic efficacy of the natural compounds was consecutively analyzed by single-dose and multiple-dose administration in diet-induced obese diabetic mice. All the natural-compounds could directly inhibit DPP-4 activity in enzymatic assay and Caco-2 inhibition assay, and HCD showed the highest inhibition of the compounds. HCD down-regulated LPS-induced ERK phosphorylation in myocyte but blocked GLP-1 induced PKA expression. For in vivo tests, HCD showed hypoglycemic efficacy only in single-dose administration. After 28-days administration, HCD exhibited hypolipidemic and hepatoprotective efficacy. These results revealed that HCD performed potential antidiabetic activity via inhibition of single-dose and long-term administrations, and could be a new prospective anti-diabetic drug candidate.

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16-Hydroxycleroda-3,13-dien-15,16-olide and N-Methyl-Actinodaphine Potentiate Tamoxifen-Induced Cell Death in Breast Cancer

Cited by 8 publications

References 27 publications

Metformin Restores the Drug Sensitivity of MCF-7 Cells Resistant Derivates via the Cooperative Modulation of Growth and Apoptotic-Related Pathways

Metformin Restores the Drug Sensitivity of MCF-7 Cells Resistant Derivates via the Cooperative Modulation of Growth and Apoptotic-Related Pathways

Diterpene 16-hydroxycleroda-3,13-dien-15,16-olide emerges non-canonical autophagic cell death in doxorubicin-resistant lung cancer

Polyalthia Clerodane Diterpene Potentiates Hypoglycemia via Inhibition of Dipeptidyl Peptidase 4

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