Strategy to enhance efficacy of doxorubicin in solid tumor cells by methyl-β-cyclodextrin: Involvement of p53 and Fas receptor ligand complex

Mohammad, Naoshad; Singh, Shivendra V.; Malvi, Parmanand; Chaube, Balkrishna; Athavale, Dipti; Vanuopadath, Muralidharan; Nair, Sudarslal Sadasivan; Nair, Bipin G.; Bhat, Manoj Kumar

doi:10.1038/srep11853

Cited by 106 publications

(76 citation statements)

References 53 publications

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“…Recent study shows that the efficacy of DOX is significantly increased by cholesterol depleting agent methyl-β-cyclodextrin (MCD) with an involvement of p53. The p53 activation has been shown to be mediated by the induction of FasR/FasL (Fas Receptor Ligand) pathway [92]. Breast cancers with positive expression of Estrogen Receptor (ER+) are treated with anti-hormone/ endocrine therapy which targets the activity of the receptor.…”

Section: Discussionmentioning

confidence: 99%

Breast cancer pathogenesis is linked to the intra-tumoral estrogen sulfotransferase (hSULT1E1) expressions regulated by cellular redox dependent Nrf-2/NFκβ interplay

Nazmeen¹,

Chen²,

Ghosh³

et al. 2020

Cancer Cell Int

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Background: Estrogen sulfotransferase catalyzes conjugation of sulfuryl-group to estradiol/estrone and regulates E2 availability/activity via estrogen-receptor or non-receptor mediated pathways. Sulfoconjugated estrogen fails to bind estrogen-receptor (ER). High estrogen is a known carcinogen in postmenopausal women. Reports reveal a potential redox-regulation of hSULT1E1/E2-signalling. Further, oxidatively-regulated nuclear-receptor-factor 2 (Nrf2) and NFκβ in relation to hSULT1E1/E2 could be therapeutic-target via cellular redox-modification. Methods: Here, oxidative stress-regulated SULT1E1-expression was analyzed in human breast carcinoma-tissues and in rat xenografted with human breast-tumor. Tumor and its surrounding tissues were obtained from the district-hospital. Intracellular redox-environment of tumors was screened with some in vitro studies. RT-PCR and western blotting was done for SULT1E1 expression. Immunohistochemistry was performed to analyze SULT1E1/Nrf2/NFκβ localization. Tissue-histoarchitecture/DNA-stability (comet assay) studies were done. Results: Oxidative-stress induces SULT1E1 via Nrf2/NFκβ cooperatively in tumor-pathogenesis to maintain the required proliferative-state under enriched E2-environment. Higher malondialdehyde/non-protein-soluble-thiol with increased superoxide-dismutase/glutathione-peroxidase/catalase activities was noticed. SULT1E1 expression and E2-level were increased in tumor-tissue compared to their corresponding surrounding-tissues. Conclusions: It may be concluded that tumors maintain a sustainable oxidative-stress through impaired antioxidants as compared to the surrounding. Liver-tissues from xenografted rat manifested similar E2/antioxidant dysregulations favoring pre-tumorogenic environment.

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Section: Discussionmentioning

confidence: 99%

Breast cancer pathogenesis is linked to the intra-tumoral estrogen sulfotransferase (hSULT1E1) expressions regulated by cellular redox dependent Nrf-2/NFκβ interplay

Nazmeen¹,

Chen²,

Ghosh³

et al. 2020

Cancer Cell Int

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“…[17,18] Juglone (5-hydroxy-1,4-naphthoquinone), present in the roots, leaves, nut hulls, bark, and wood of the black walnuts, possesses antimicrobial, anti-inflammatory, immunomodulatory, diuretic, and laxative properties. [20,21] Juglone also acts as a natural inhibitor of Pin1, which is elevated in cancerous conditions. [20,21] Juglone also acts as a natural inhibitor of Pin1, which is elevated in cancerous conditions.…”

Section: Introductionmentioning

confidence: 99%

Indomethacin and juglone inhibit inflammatory molecules to induce apoptosis in colon cancer cells

Seetha

Devaraj

Sudhandiran

2020

J Biochem & Molecular Tox

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Colorectal cancer (CRC) is the third most common fatal cancer. Indomethacin, a nonsteroidal anti-inflammatory drug, is known to reduce the occurrence of CRC.This study evaluated the potential anticolon cancer effects of juglone (5-hydroxy-1,4-naphthoquinone) in combination with indomethacin. Human colon adenocarcinoma cells (HT29) were subjected to treatment with indomethacin, juglone, and a combination of both. Morphological analysis, cell cycle regulation, and dual staining using acridine orange and ethidium bromide in control and treated cells revealed the apoptotic potential of these compounds. Bcl2 and inflammatory molecules (tumor necrosis factor-α, nuclear factor kappa B, and Cox-2) were found to be decreased with a concomitant increase in the expression of proapoptotic molecules (Bad, Bax, cytochrome c, and PUMA) as a result of the molecular regulation of Wnt, Notch, and peroxisome proliferator-activated receptor-γ signaling. Treatment with juglone was not as effective as with indomethacin; however, a combination of both was shown to be more effective, suggesting that juglone may be considered for therapeutic intervention of colon cancer.

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“…Tumor growth was retarded and survival increased in mice that were administered methyl-β-cyclodextrin together with doxorubicin to as compared to either agent alone. 32 Combined with modern experimental research, emodin has antitumor effect with low toxicity and has synergistic effect with various antitumor drugs, which is a potential effective drug for clinical tumor treatment. 33 Therefore, we aimed at emodin which is a natural product.…”

Section: Discussionmentioning

confidence: 99%

<p>Emodin sensitizes human pancreatic cancer cells to EGFR inhibitor through suppressing Stat3 signaling pathway</p>

Wang¹,

Chen²,

Chen³

et al. 2019

CMAR

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Background: Excessive expression of EGFR is closely related to tumor formation, transfer and deterioration, which has attracted much attention. EGFR overexpression may be detected in up to 90% of pancreatic tumors. However, drug resistance of EGFR inhibitors targeting treatment severely limits its clinical application. Methods: In this study, Western blotting was used to detect the expression of p-Stat3, EGFR, Bcl-2, cleaved-caspase3 and Bax. Cell apoptosis was evaluated via flow cytometry. The colon assay and MTT assay were applied for detecting the cell proliferation in vitro. The xenograft mouse model was used to examine the cell proliferation in vivo. Results: Emodin remarkably enhanced the anti-cancer effect of EGFR inhibitor on pancreatic cancer cells. In addition, emodin promoted afatinib-induced apoptosis by inhibiting the Stat3 signaling pathway. Meanwhile, siRNAs against Stat3 significantly increased the apoptosis of pancreatic cancer cells. EGFR inhibitor promoted phosphorylation of Stat3 in pancreatic cancer cells. Interestingly, emodin combined with EGFR inhibitor inhibited the proliferation of pancreatic cancer cells in vitro. The tumor xenograft mice model was further confirmed that emodin possessed a synergy anticancer effect with afatinib on pancreatic cancer cells by regulating the Stat3 expression. Conclusion: These results indicate that the combination of emodin with EGFR inhibitor is an effective therapeutic strategy to sensitize human pancreatic cancer.

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Strategy to enhance efficacy of doxorubicin in solid tumor cells by methyl-β-cyclodextrin: Involvement of p53 and Fas receptor ligand complex

Cited by 106 publications

References 53 publications

Breast cancer pathogenesis is linked to the intra-tumoral estrogen sulfotransferase (hSULT1E1) expressions regulated by cellular redox dependent Nrf-2/NFκβ interplay

Breast cancer pathogenesis is linked to the intra-tumoral estrogen sulfotransferase (hSULT1E1) expressions regulated by cellular redox dependent Nrf-2/NFκβ interplay

Indomethacin and juglone inhibit inflammatory molecules to induce apoptosis in colon cancer cells

<p>Emodin sensitizes human pancreatic cancer cells to EGFR inhibitor through suppressing Stat3 signaling pathway</p>

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