scholarly journals Insights into the mechanism of antiproliferative effects of primaquine-cinnamic acid conjugates on MCF-7 cells

2018 ◽  
Vol 68 (3) ◽  
pp. 337-348 ◽  
Author(s):  
Peace Mabeta ◽  
Kristina Pavić ◽  
Branka Zorc

Abstract In our previous paper, we showed that three primaquine-cinnamic acid conjugates composed of primaquine (PQ) residue and cinnamic acid derivatives (CADs) bound directly by an amide linkage (1) or through an acylsemicarbazide spacer (2 and 3) had significant growth inhibitory effects on some cancer cell lines. Compound 1 induced significant growth inhibition in the colorectal adenocarcinoma (SW620), human breast adenocarcinoma (MCF-7) and cervical carcinoma (HeLa) cell lines, while compounds 2 and 3 selectively inhibited the growth of MCF-7 cells. To better understand the underlying mechanisms of action of these PQ-CADs, morphological studies of the effects of test compounds on MCF-7 cells were undertaken using haematoxylin and eosin stain. Further analysis to determine the effects of test compounds on caspase activity and on the levels of apoptosis proteins were undertaken using the enzyme-linked immunosorbent assay (ELISA). Haematoxylin and eosin staining revealed that compounds 1 and 3 induced morphological changes in MCF-7 cells characteristic of apoptosis, while 2-treated cells were in interphase. Cell cycle analysis showed that cells treated with 1 and 3 were in sub-G1, while cells treated with 2 were mainly in interphase (G1 phase). Further, the study showed that the treatment of MCF-7 cells with 1 and 3 resulted in poly ADP ribose polymerase (PARP) cleavage as well as caspase-9 activation, indicating that they induced apoptotic cell death. We further investigated their effects on two important processes during metastasis, namely, migration and invasion. Compounds 1 and 3 inhibited the migration and invasion of MCF-7 cells, while compound 2 had a marginal effect.

Author(s):  
Chen Shi ◽  
Yue-Ling Peng ◽  
Juan He ◽  
Zheng-Hui Li ◽  
Ji-Kai Liu ◽  
...  

AbstractTwo undescribed Tricholoma triterpenoids, namely tricholopardins C (1) and D (2), were isolated from the wild mushroom Tricholoma pardinum. Their structures with absolute configurations were elucidated by spectroscopic methods, as well as the single crystal X-ray diffraction. Compounds 1 and 2 were further obtained by chemical conversions from the known analogues. Compound 1 showed significant cytotoxicity to MCF-7 and Hela cell lines with IC50 values of 4.7 μM and 9.7 μM, respectively. Its mechanism of inducing MCF-7 cell apoptosis was studied briefly. Graphical Abstract


2020 ◽  
Vol 9 (5) ◽  
pp. 367-370
Author(s):  
BN Satish ◽  
◽  
Mallya Suma V ◽  
Vishwanatha ◽  
◽  
...  

About: Habenaria longicorniculata J. Graham are tuberous orchid, the tubers utilized by flok healers in cancer managemnet, as a rejuvenator. A study has been planned to evaluate In-vitro cytotoxicity of tuber extract against selected cell lines. Materials and Methods: H. longicorniculata J.Graham identified, uprooted during their flowering time. Tuber extract of this plant used for its In-vitro cytotoxicity against selected cell lines of Human Breast cancer (MCF 7), Human Liver carcinoma (HepG2), and Human cervix adenocarcinoma (HeLa) cells as per standard protocol. Results: Tuber Extract exhibited a CTC50 value of >1000 on MCF 7, HepG2 and HeLa cell lines. The results from the MTT assay indicate that 72hr extract incubation with the combined extracts is toxic to the cells and the level of damage is concentration dependent.


2021 ◽  
Vol 71 (2) ◽  
pp. 245-266
Author(s):  
Qingfang Zeng ◽  
Cairong Luo ◽  
Junlae Cho ◽  
Donna Lai ◽  
Xiangchun Shen ◽  
...  

AbstractTryptanthrin is an indole quinazoline alkaloid from the indigo-bearing plants, such as Isatis indigotica Fort. Typically, this natural compound shows a variety of pharmacological activities such as antitumor, antibacterial, anti-inflammatory and antioxidant effects. This study was conducted to assess the antitumor activity of tryptanthrin in breast cancer models both in vitro and in vivo, and to explore the important role of the inflammatory tumor microenvironment (TME) in the antitumor effects of tryptanthrin. Human breast adenocarcinoma MCF-7 cells were used to assess the antitumor effect of tryptanthrin in vitro. MTT assay and colony formation assay were carried out to monitor the antiproliferative effect of tryptanthrin (1.56~50.0 μmol L−1) on inhibiting the proliferation and colony formation of MCF-7 cells, respectively. The migration and invasion of MCF-7 cells were evaluated by wound healing assay and Transwell chamber assay, respectively. Moreover, the 4T1 murine breast cancer model was established to examine the pharmacological activity of tryptanthrin, and three groups with different doses of tryptanthrin (25, 50 and 100 mg kg−1) were set in study. Additionally, tumor volumes and organ coefficients were measured and calculated. After two weeks of tryptanthrin treatment, samples from serum, tumor tissue and different organs from tumor-bearing mice were collected, and the enzyme-linked immunosorbent assay (ELISA) was performed to assess the regulation of inflammatory molecules in mouse serum. Additionally, pathological examinations of tumor tissues and organs from mice were evaluated through hematoxylin and eosin (H&E) staining. The expression of inflammatory proteins in tumor tissues was measured by immunohistochemistry (IHC) and Western blotting. Tryptanthrin inhibited the proliferation, migration and invasion of MCF-7 cells, up-regulated the protein level of E-cadherin, and down-regulated those of MMP-2 and Snail, as suggested by the MCF-7 cell experiment. According to the results from in vivo experiment, tryptanthrin was effective in inhibiting tumor growth, and it showed favorable safety without inducing the fluctuations of body mass and organ coefficient (p > 0.05). In addition, tryptanthrin also suppressed the expression levels of NOS1, COX-2 and NF-κB in mouse tumor tissues, and regulated those of IL-2, IL-10 and TNF-α in the serum of tumor cells-transplanted mice. Tryptanthrin exerted its anti-breast cancer activities through modulating the inflammatory TME both in vitro and in vivo.


2011 ◽  
Vol 47 (2) ◽  
pp. 279-287 ◽  
Author(s):  
Angel Treasa Thomas ◽  
Josyula Venkata Rao ◽  
Volety Mallikarjuna Subrahmanyam ◽  
Hariharapura Raghu Chandrashekhar ◽  
Naseer Maliyakkal ◽  
...  

Extracts from natural products, especially microorganisms, have served as a valuable source of diverse molecules in many drug discovery efforts and led to the discovery of several important drugs. Identification of microbial strains having promising biological activities and purifying the bio-molecules responsible for the activities, have led to the discovery of many bioactive molecules. Extracellular, as well as intracellular, extracts of the metabolites of thirty-six bacterial and twenty-four fungal isolates, grown under unusual conditions such as high temperature, high salt and low sugar concentrations, were in vitro tested for their cytotoxic potential on various cancer cell lines. The extracts were screened on HeLa and MCF-7 cell lines to study the cytotoxic potential. Nuclear staining and flow cytometric studies were carried out to assess the potential of the extracts in arresting the cell cycle. The crude ethylacetate extract of isolate F-21 showed promising results by MTT assay with IC50 as low as 20.37±0.36 µg/mL on HeLa, and 44.75±0.81 µg/mL on MCF-7 cells, comparable with Cisplatin. The isolate F-21 was identified as Aspergillus sp. Promising results were also obtained with B-2C and B-4E strains. Morphological studies, biochemical tests and preliminary chemical investigation of the extracts were also carried out.


2017 ◽  
Vol 93 (8) ◽  
pp. 757-763 ◽  
Author(s):  
Karim Khoshgard ◽  
Parvaneh Kiani ◽  
Abbas Haghparast ◽  
Leila Hosseinzadeh ◽  
Mohammad Taghi Eivazi

2020 ◽  
Author(s):  
Esraa Ahmed Mohamed El-Bondkly ◽  
Mervat Morsy El-Gendy ◽  
Aya Ahmed Mohamed El-Bondkly ◽  
Fareed Shawky El-Shenawy ◽  
Alaa Ahmed Mohamed El-Bondkly

Abstract In this investigation three ancient Egyptian medical plants; Plantago albicans L., Thymelaea hirsuta (L.) Endl. and Urginea maritima (L.) were chosen to explore their biochemical properties, anticancer and antimycotic activities against clinical dermatophytes. Growing of Trichophyton soudanense, Trichophyton erinacei, Microsporum audouinii, Microsporum gypseum, Microsporum gallinae, Microsporum ferrogenium, Microsporum cookie, Microsporum racemosum, Microsporum persicolor and Microsporum canis were totally inhibited by the 100 µg/mL of P. albicans methanolic extract. Whereas the growth of T. soudanense, T. erinacei, Trichophyton rubrum, Trichophyton tonsurance and Trichophyton mentagrophytes and Epidermophyton floccosum were 100% inhibited by the methanolic extract of T. hirsiuta at 100 µg/mL concentration, however its acetone extract was more active against Microsporum species. The highest fungi toxicity against all dermatophytic fungi was detected in both methanol and acetone extract of U. maritima at a concentration ranged between 50 to 100 µg/mL. Methanolic extract of P. albicans inhibited the viability of HCT-116, HepG-2, MCF-7 and HeLa cell lines by (41%, 40%, 80% and 81%); (30%, 20%, 66% and 70%); (19%, 0%, 49% and 57%); (5%, 0%, 35% and 45%) and (0%, 0%, 21% and 40%) at 25, 50, 100, 200 and 300 µg/mL, respectively. Moreover, the cells death after treatment with the same concentrations of T. hirsuta methanol extract were (10%, 20%, 23% and 60%); (16%, 40%, 58% and 80%); (40%, 50%, 80% and 100%); (51%, 65%, 100% and 100%) and (49%, 82%, 100% and 100%) in HCT-116, HepG-2, MCF-7 and HeLa cells, respectively. Viability of HCT-116, MCF-7 and HepG-2 cell lines was totally suppressed with 100 µg/mL whereas the HeLa cell growth was reduced to 10% and totally killed at 100 and 200 µg/mL, respectively of U. maritima methanolic extract. All data approve the significance of Egyptian ethnomedical plants as potent source of diverse bioactive pharmaceutical metabolites.


2021 ◽  
Vol 12 ◽  
Author(s):  
Chunmei Sai ◽  
Wei Qin ◽  
Junyu Meng ◽  
Li-Na Gao ◽  
Lufen Huang ◽  
...  

Macleayins A (MA), a novel compound, was isolated from Macleaya cordata (Willd.) R. Br. and Macleaya microcarpa (Maxim.) Fedde. The plant species are the member of Papaveraceae family and have been used traditionally for diverse therapeutic purposes. According to the reported studies, the chemical constituents, as well as crude extracts of these plants, could attenuate the proliferation of several cancer cell lines, such as HL-60, A549, HepG2, and MCF-7. The current study aimed to investigate the anticervical cancer activity of MA and its related molecular mechanism. Isolation of MA was carried out using various column chromatographic methods, and its structure was elucidated with 1H NMR. The cytotoxicity of MA was determined against HeLa cell lines via CCK-8 assay. The cell proliferation, apoptosis, cell cycle, migration, and invasion were measured by EdU labeling, Annexin-V APC/7-AAD double staining, PI staining, and transwell assay, respectively. The protein expression levels of c-Myc, β-catenin, cyclin D1, and MMP-7 in the cells were evaluated by western blotting. The Wnt/β-catenin signaling cascade activation was verified using the Dual-Glo® Luciferase assay. We found that MA inhibited the growth of HeLa cells at 72 h (IC50 = 26.88 µM) via inducing apoptotic process, reduced the proliferation rate by 29.89%, and decreased the cells migration and invasion as compared to the untreated group. It arrested the cell cycle at the G1 phase and its treatment inhibited the expression of related proteins c-Myc, β-catenin, cyclin D1, and MMP-7 in the Wnt/β-catenin signaling cascade. Further, the Wnt/β-catenin signaling cascade activation in MA-treated HeLa cells was attenuated in a dose-dependent manner. These findings demonstrate the anticancer effects of MA on a mechanistic level, thus providing a basis for MA to become a potential candidate drug for resistance of cervical carcinoma.


Author(s):  
WM Farhan Syafiq B WM Nor ◽  
Ivy Chung ◽  
Nur Akmarina B M Said

Breast cancer is the most commonly diagnosed cancer among women and one of the leading causes of cancer mortality worldwide, in which the most severe form happens when it metastasizes to other regions of the body. Metastasis is responsible for most treatment failures in advanced breast cancer. Epithelial-mesenchymal transition (EMT) plays a significant role in promoting metastatic processes in breast cancer. MicroRNAs (miRNAs) are highly conserved endogenous short non-coding RNAs that play a role in regulating a broad range of biological processes, including cancer initiation and development, by functioning as tumor promoters or tumor suppressors. Expression of miR-548m has been found in various types of cancers, but the biological function and molecular mechanisms of miR-548m in cancers have not been fully studied. Here, we demonstrated the role of miR-548m in modulating EMT in the breast cancer cell lines MDA-MB-231 and MCF-7. Expression data for primary breast cancer obtained from NCBI GEO datasets showed that miR-548m expression was downregulated in breast cancer patients compared with healthy group. We hypothesize that miR-548m acts as a tumor suppressor in breast cancer. Overexpression of miR-548m in both cell lines increased E-cadherin expression and decreased the EMT-associated transcription factors SNAI1, SNAI2, ZEB1 and ZEB2, as well as MMP9 expression. Consequently, migration and invasion capabilities of both MDA-MB-231 and MCF-7 cells were significantly inhibited in miR-548m-overexpressing cells. Analysis of 1059 putative target genes of miR-548m revealed common pathways involving both tight junction and the mTOR signaling pathway, which has potential impacts on cell migration and invasion. Furthermore, this study identified aryl hydrocarbon receptor (AHR) as a direct target of miR-548m in breast cancer cells. Taken together, our findings suggest a novel function of miR-548m in reversing the EMT of breast cancer by reducing their migratory and invasive potentials, at least in part via targeting AHR expression.


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