Evaluation of the cytotoxic and apoptogenic effects of cinnamaldehyde on U87MG cells alone and in combination with doxorubicin

Abbasi, Abbas; Hajialyani, Marziyeh; Hosseinzadeh, Leila; Jalilian, Fereshteh; Yaghmaei, Parichehreh; Navid, Sahar Jamshidi; Motamed, Hajar

doi:10.4103/1735-5362.278712

Cited by 20 publications

(9 citation statements)

References 24 publications

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“…Briefly, the confluent cells (1×10 6 cells per well in 6-well plates) were incubated with the culture medium containing different CA preparations (MSN CA @GO DOX -HA, MSN CA @GO DOX , MSN CA and free CA, adjusted to 40μg/mL according to the concentration of free CA) or DOX preparations (MSN CA @GO DOX , GO DOX and free DOX solutions, adjusted to 5μg/mL according to the concentration of free DOX) for 24h. 25 Subsequently, cells were trypsinized and centrifuged at 1000rpm, then lysed with lysis buffer (50μL) and incubated on ice for 15min. The protein content of cells was extracted by the centrifugation of lysates (16,000–20,000rpm) at 4°C for 10min.…”

Section: Methodsmentioning

confidence: 99%

“…Recently, several studies revealed that the combination of CA and DOX significantly promoted the apoptosis and necrosis of tumor cells, which was much better than either of them. [23][24][25] However, the clinical application of CA is still limited due to its poor chemical stability and rapid clearance (short half-lives in human plasma) caused by the rapid oxidation of its aldehyde group, and the DOX also induced many side-effects (eg cardiotoxicity, skeletal muscle dysfunction and myelosuppression) due to the lack of effective tumor targeting mechanism. [26][27][28][29][30] Therefore, in this study, CA was first introduced into the tunnel structure of aminated MSN (MSN-NH 2 ), and GO was modified with HA and loaded DOX via π-π stacking.…”

Section: Introductionmentioning

confidence: 99%

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<p>Cinnamaldehyde and Doxorubicin Co-Loaded Graphene Oxide Wrapped Mesoporous Silica Nanoparticles for Enhanced MCF-7 Cell Apoptosis</p>

Dong¹,

Zhao²,

Kang³

et al. 2020

IJN

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Background Combined chemotherapy is often affected by the different physicochemical properties of chemotherapeutic drugs, which should be improved by the reasonable design of co-loaded preparations. Purpose A kind of simple but practical graphene oxide (GO) wrapped mesoporous silica nanoparticles (MSN) modified with hyaluronic acid (MSN@GO-HA) were developed for the co-delivery of cinnamaldehyde (CA) and doxorubicin (DOX), in order to enhance their combined treatment on tumor cells and reduce their application defects. Methods The MSN CA @GO DOX -HA was constructed by MSN CA (loading CA via physical diffusion) and GO DOX -HA (modified with HA and loading DOX via π–π stacking) through the electrostatic adsorption, followed by the physicochemical characterization, serum stability and in vitro release study. Cytotoxicity on different cells was detected, followed by the tumor cell uptake tests. The intracellular reactive oxygen species (ROS) changes, mitochondrial functions and activities of caspase-3/-9 in MCF-7 cells were also evaluated, respectively. Results The MSN CA @GO DOX -HA nanoparticles kept stable in FBS solution and achieved pH-responsive release behavior, which was beneficial to increase the accumulation of CA and DOX in tumor cells to enhance the treatment. MSN CA @GO DOX -HA exerted higher cytotoxicity to MCF-7 human breast cancer cells than H9c2 cardiac myocyte cells, which were not only attributed to the active targeting to tumor cells by HA, but also related with the activation of intrinsic apoptotic pathway in MCF-7 cells induced by CA, which was mediated by the specific ROS signal amplification and the interference with mitochondrial function. Moreover, the efficacy of DOX was also enhanced by the above process. Conclusion The establishment of the MSN CA @GO DOX -HA nanoparticles played a role in promoting strengths and restricting shortcomings of CA and DOX, thereby exerting their function and achieving efficient treatment against cancer.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

<p>Cinnamaldehyde and Doxorubicin Co-Loaded Graphene Oxide Wrapped Mesoporous Silica Nanoparticles for Enhanced MCF-7 Cell Apoptosis</p>

Dong¹,

Zhao²,

Kang³

et al. 2020

IJN

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“…Cinnamaldehyde has been found to be cytotoxic on several cancer cell lines, such as leukemia K562 [ 41 ] and breast cancer MCF-7 cells [ 42 ]. Furthermore, cinnamaldehyde has been found to be a promising adjuvant candidate in combination with 5-fluorouracil and oxaliplatin against colorectal carcinoma [ 43 ], and to enhance the apoptosis induced by hyperthermia against the A549 cells [ 44 ] and by doxorubicin on glioblastoma cells (U87MG) [ 45 ]. This cytotoxicity of cinnamaldehyde may be due to the presence of an electrophilic Michael acceptor (α,β-unsaturated aldehyde) pharmacophore, which has been anticipated to provide this scaffold with a potential anticancer activity [ 46 ].…”

Section: Resultsmentioning

confidence: 99%

Design, Synthesis, Biological Evaluation and In Silico Study of Benzyloxybenzaldehyde Derivatives as Selective ALDH1A3 Inhibitors

et al. 2021

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Aldehyde dehydrogenase 1A3 (ALDH1A3) has recently gained attention from researchers in the cancer field. Several studies have reported ALDH1A3 overexpression in different cancer types, which has been found to correlate with poor treatment recovery. Therefore, finding selective inhibitors against ALDH1A3 could result in new treatment options for cancer treatment. In this study, ALDH1A3-selective candidates were designed based on the physiological substrate resemblance, synthesized and investigated for ALDH1A1, ALDH1A3 and ALDH3A1 selectivity and cytotoxicity using ALDH-positive A549 and ALDH-negative H1299 cells. Two compounds (ABMM-15 and ABMM-16), with a benzyloxybenzaldehyde scaffold, were found to be the most potent and selective inhibitors for ALDH1A3, with IC50 values of 0.23 and 1.29 µM, respectively. The results also show no significant cytotoxicity for ABMM-15 and ABMM-16 on either cell line. However, a few other candidates (ABMM-6, ABMM-24, ABMM-32) showed considerable cytotoxicity on H1299 cells, when compared to A549 cells, with IC50 values of 14.0, 13.7 and 13.0µM, respectively. The computational study supported the experimental results and suggested a good binding for ABMM-15 and ABMM-16 to the ALDH1A3 isoform. From the obtained results, it can be concluded that benzyloxybenzaldehyde might be considered a promising scaffold for further drug discovery aimed at exploiting ALDH1A3 for therapeutic intervention.

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“…Evidences have shown that due to the high content of polyunsaturated fatty acids, the nervous system has particularly been vulnerable to oxidative stress ( 1 ). Also, doxorubicin (DOX) as a highly effective chemotherapy medication for the treatment of a wide variety of tumors, rises levels of reactive oxygen species (ROS) resulting in inducing oxidative stress ( 2 3 ). The overproduction of ROS causes damage in organelles’ functions such as mitochondria ( 4 ).…”

Section: Introductionmentioning

confidence: 99%

Oxypeucedanin and isoimperatorin extracted from Prangos ferulacea (L.) Lindl protect PC12 pheochromocytoma cells from oxidative stress and apoptosis induced by doxorubicin

et al. 2022

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Background and purpose: Doxorubicin (DOX) as a chemotherapeutic agent has been widely used in the treatment of various types of cancer. However, DOX exerts a toxic effect on normal tissues such as the brain. Furanocoumarins reduce the risk of cardiovascular and brain diseases because of their antioxidant activities. This study has been designed, for the first time, to evaluate the effect of known furanocoumarins oxypeucedanin and isoimperatorin extracted from Prangos ferulacea (L.) Lindl on oxidative stress and apoptosis induced by DOX toward pheochromocytoma cell line (PC12). Experimental approach: NMR and MASS spectrometers were used to characterize the isolated compounds. The protective effects of isolated compounds on DOX-induced cytotoxicity in PC12 cells were examined by MTT assay. PC12 cells were pretreated with oxypeucedanin and isoimperatorin for 2 and 21 h, respectively, subsequently exposure to DOX at IC 50 concentration. Then, mitochondrial membrane potential (MMP), Bax and Bcl2 mRNA expressions, caspase-3 activation, and the generation of intracellular reactive oxygen species (ROS) were measured after 24 h. Findings/Results: Pretreatment with oxypeucedanin and isoimperatorin significantly decreased DOX-induced apoptosis through reduction of caspase-3 activity and ROS generation and an increase in MMP. In addition, our finding showed pretreatment with these compounds leads to regulation of Bcl-2. Conclusion and implications: Taken together our observation indicated that oxypeucedanin and isoimperatorin have a protective effect against apoptosis induced by DOX in PC12 cells by inhibition of ROS production.

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Evaluation of the cytotoxic and apoptogenic effects of cinnamaldehyde on U87MG cells alone and in combination with doxorubicin

Cited by 20 publications

References 24 publications

<p>Cinnamaldehyde and Doxorubicin Co-Loaded Graphene Oxide Wrapped Mesoporous Silica Nanoparticles for Enhanced MCF-7 Cell Apoptosis</p>

<p>Cinnamaldehyde and Doxorubicin Co-Loaded Graphene Oxide Wrapped Mesoporous Silica Nanoparticles for Enhanced MCF-7 Cell Apoptosis</p>

Design, Synthesis, Biological Evaluation and In Silico Study of Benzyloxybenzaldehyde Derivatives as Selective ALDH1A3 Inhibitors

Oxypeucedanin and isoimperatorin extracted from Prangos ferulacea (L.) Lindl protect PC12 pheochromocytoma cells from oxidative stress and apoptosis induced by doxorubicin

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