Identification of two novel thiophene analogues as inducers of autophagy mediated cell death in breast cancer cells

Gain, Chandrima; Sarkar, Arindam; Bural, Shrea; Rakshit, Moumita; Banerjee, Joydeep; Dey, Ankita; Biswas, Nabendu; Kar, Gandhi K.; Saha, Abhik

doi:10.1016/j.bmc.2021.116112

Cited by 6 publications

(3 citation statements)

References 67 publications

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“…The vast majority of studies focused on inhibiting autophagy to prevent the renewal of cellular proteins and other molecules that help cancer cells survive under stressful conditions such as hypoxia and nutrient deprivation and to enhance other cancer treatments including chemotherapy and radiation [24]. However, some scientists focused on using natural compounds to activate overautophagy and cause cell death [22,25,26].…”

Section: Discussionmentioning

confidence: 99%

The Synergistic Effects of Celastrol in combination with Tamoxifen on Apoptosis and Autophagy in MCF-7 Cells

Wang

Tang

Yao

et al. 2021

Journal of Immunology Research

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Breast cancer is one of the most common cancers among females and is associated with high mortality and morbidity rates. Several studies have demonstrated that combination treatments with natural products and tamoxifen can improve the sensitivity and cytotoxicity of oestrogen-positive breast cancer cells in response to tamoxifen. Celastrol, a triterpene from traditional Chinese medicine, has been proven to exert significant anticancer effects on various cancers. Our study is aimed at exploring the interactive antitumour effects of celastrol combined with tamoxifen and the potential underlying anticancer mechanisms in MCF-7 cells. The results from MTT assays, isobolographic analyses, and clonogenic cell survival assays revealed that a combination of celastrol and tamoxifen exerted synergistic cytotoxic effects in MCF-7 cells. The results from Annexin V/PI staining and flow cytometry analysis suggested that celastrol enhanced tamoxifen-mediated apoptosis. In addition, exposure to a combination of celastrol and tamoxifen inhibited cell proliferation by causing G1 phase cell cycle arrest. Moreover, the distribution of LC3 was monitored by immunofluorescence, and the changes in the LC3II and P62 levels detected by western blot analysis suggested that celastrol in combination with tamoxifen triggered autophagy. Furthermore, the decrease in p-Akt and p-mTOR in MCF-7 cells, along with the increase in the autophagy marker proteins LC3II and P62, suggested that the Akt/mTOR pathway might be involved in the triggering of cell autophagy by the combination treatment. However, in an MCF-7-implanted nude mouse model, it was possible to detect significantly decreased tumour volumes and tumour weights and decreased p-Akt and p-mTOR protein expression in the celastrol+tamoxifen group. Therefore, our study provides the first evidence that celastrol combined with tamoxifen exerts synergistic anticancer effects by inducing apoptosis and autophagy in MCF-7 cells. Considering the urgent need for novel therapeutic strategies in anticancer therapy, this combinatorial approach is worthy of further investigation.

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Section: Discussionmentioning

confidence: 99%

The Synergistic Effects of Celastrol in combination with Tamoxifen on Apoptosis and Autophagy in MCF-7 Cells

Wang

Tang

Yao

et al. 2021

Journal of Immunology Research

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“…Based on these limitations, it is necessary to optimize tanshinone’s structure and increase antitumor potency and drug-like properties. A recent study identified two tanshinone analogs, which increased antitumor potency as compared to the natural tanshinones both Tan-I and Tan-IIA ( Gain et al, 2021 ).…”

Section: Conclusion and Expectationmentioning

confidence: 99%

Anticancer Effect of Tanshinones on Female Breast Cancer and Gynecological Cancer

Zhou

Peng

2022

Front. Pharmacol.

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Female breast cancer, ovarian cancer, cervical cancer, and endometrial cancer are the most common tumors and the most common causes of cancer-related mortality worldwide in women. Drugs derived from natural plants play important roles in malignant tumor therapy. Salvia miltiorrhiza is a commonly used Chinese herb which has been used in the treatment of liver diseases and cardiovascular diseases because of its positive effect of promoting blood circulation, increasing oxidative stress, and removing blood stasis. Recently, studies have found that fat-soluble components of Salvia miltiorrhiza such as tanshinone II, tanshinone I, cryptotanshinone, and dihydrotanshinone I displayed good antitumor activity in vivo and in vitro for gynecological cancer by different molecular mechanisms. In this study, the latest research progress on the antitumor effect and mechanism of tanshinone compounds in breast cancer and gynecological cancer was reviewed to provide references for the research and clinical application of these compounds (tanshinone II, tanshinone I, cryptotanshinone, and dihydrotanshinone I).

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“…Furthermore, and according to the literature, thiophene-based compounds have applications ranging from anti-cancer chemotherapy to the treatment of a variety of other diseases [27,28]. Several human tumor cell lines, including cervical cancer, gastric cancer, colorectal cancer, oesophageal cancer, lung cancer, hepatocellular carcinoma, oral cancer, osteosarcoma, prostate cancer, ovarian cancer, and breast carcinoma, have shown inhibitory activity in vitro and in vivo [29][30][31][32][33][34][35][36]. The chloroacetamides possess key structural features, including an easy replacement of chlorine atoms, which make them highly attractive synthetic platforms for synthesizing diverse heterocyclic systems.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of some new thiophene-based compounds and evaluations of their cytotoxic activities

Mehdhar¹,

Alzahrani²,

Abdel‐Galil³

et al. 2022

Bull. Chem. Soc. Eth.

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ABSTRACT. A series of new thiophene derivatives was prepared through nucleophilic substitution reactions of the precursor N-(4-substituted-phenyl)-5-(2-chloroacetamido)-4-cyano-3-methylthiophene-2-‎carboxamides 4a and 4b with different sulfur and/or nitrogen nucleophilic reagents (namely; mercaptoacetic acid, 2-mercaptobenzothiazole, 5-(phenylamino)-1,3,4-thiadiazole-2-thiol, 2-mercapto-4,6-dimethylnicotinonitrile, 3-arylazo-4-mercapto-4-(phenylamino)-but-3-en-one derivatives, ammonium thiocyanate, piperidine and/or morpholine). The structures of the prepared thiophene compounds were characterized by spectral analysis. Their cytotoxicity was evaluated against two human cancer cell lines (HepG2 and MCF-7) and indicated promising results. Pretreatment of HepG2 cells with the tested compound 4b sensitized the cells to the cytotoxicity of sorafenib, leading to a significant decrease in the IC50 from 3.9 to 0.5 µM. KEY WORDS: N-(Thienyl)-2-chloroacetamide, Bis-thiophene, Thieno[2,3-d]pyrimidine, Ammonium thiocyanate, Cytotoxicity Bull. Chem. Soc. Ethiop. 2023, 37(2), 373-389. DOI: https://dx.doi.org/10.4314/bcse.v37i2.10

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Identification of two novel thiophene analogues as inducers of autophagy mediated cell death in breast cancer cells

Cited by 6 publications

References 67 publications

The Synergistic Effects of Celastrol in combination with Tamoxifen on Apoptosis and Autophagy in MCF-7 Cells

The Synergistic Effects of Celastrol in combination with Tamoxifen on Apoptosis and Autophagy in MCF-7 Cells

Anticancer Effect of Tanshinones on Female Breast Cancer and Gynecological Cancer

Synthesis of some new thiophene-based compounds and evaluations of their cytotoxic activities

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