Apoptosis-inducing Activity Research Articles

Investigation of antiproliferative and apoptotic effects of Rosmarinus officinalis essential oil obtained by hydrodistillation on neuroblastoma cells

This study was designed to determine the potential antiproliferative and apoptosis inducing activities of Rosmarinus officinalis essential oil (RE) on neuroblastoma cancer cells. For this purpose, different concentrations of RE were applied to SH-SY5Y cells for 24 hours and cell viability was determined by MTT. In addition, the percentage of early, late and non-apoptotic cells was determined by AnnexinV/propodium iodide staining to determine the induction of apoptosis. In addition, the composition of RE was determined by GC-MS. In MTT assay, it was determined that the viability of SH-SY5Y cells decreased dose-dependently as a result of the application of different concentrations of RE. Moreover, 200 mg/ml RE treatment increased the percentage of cells in the late apoptotic phase. The main compounds of RE were determined as (1R)-2,6,6-Trimethylbicyclo[3.1.1]hept-2-ene, Bicyclo[3.1.1]hept-3-en-2-one, 4,6,6-trimethyl, 1,8-Cineole, Camphor by GC-MS. In conclusion, RE is thought to be an important source of anti-proliferative and apoptosis inducing activity on neuroblastoma cells.

DNA binding, and apoptosis-inducing activities of a β-ionone-derived ester in human myeloid leukemia cells: multispectral and molecular dynamic simulation analyses

β-Ionone is the end-ring counterpart of β-carotenoids, which are widely found in fruits and vegetables. Recent studies have illustrated the antimetastatic, anti-proliferative, and apoptosis-inducing activities of β-ionone both in vitro and in vivo. We aimed to explore the anti-cancer potency of β-Ionone-derived ester, (E)-4-(2,6,6-trimethylcyclohex-1-enyl) but-3-en-2-ylpyrazine-2-carboxylate (4-TM.P). The cytotoxic effects of the compound on K562 cells were evaluated by MTT assay. The mechanisms of apoptosis induction were investigated by acridine orange/ethidium bromide (AO/EtBr) double staining, cell cycle analysis, and Annexin V/PI staining. Furthermore, the 4-TM.P-DNA interactions have been thoroughly elucidated by various methods, such as ultraviolet–visible spectroscopy, fluorescence assays, viscosity measurements, molecular docking, and dynamic simulation. The MTT cytotoxicity assay revealed that the growth of K562 cells was inhibited by treatment with β-ionone-derived ester, with an IC50 of 25 ± 5.0 µM at 72 h. Morphological studies revealed the occurrence of apoptosis in treated cells, and G0/G1 cell cycle arrest was observed after treatment of the cells with the IC50 value of the compound. Analyses of multi-spectroscopy and viscosity assays revealed that 4-TM.P binds to DNA in the minor groove mode, which was supported by molecular docking studies. The dynamic stability of the complex was also confirmed using molecular dynamic simulation analyses.

Evaluation of Anti-Proliferative and Apoptosis-Inducing Activities of the New Ciprofloxacin Derivative on Human Leukemia NB4 Cells

Backgrounds:: Leukemic stem cells are considered to be the main cause of treatment failure and disease recurrence due to their resistance to most common therapies. Apoptosis induction is one of the highly effective methods for treating cancer. Ciprofloxacin is among the compounds whose antitumor effects have been confirmed. Objectives: In this study, we investigated the anti-proliferative effect and induction of apoptosis by one of the derivatives of this family called 1-Cyclopropyl-6-fluoro-7-[4-(2-{[(1R,2S,5R)- 2- isopropyl-5-methylcyclohexyl]oxy}-2-oxoethyl)-piperazin-1-yl]-4-oxo-1,4-dihydroquinoline-3- carboxylic acid (ICH-CP) on NB4 cell line as an in vitro model of Acute promyelocytic leukemia (APL). NB4 cells were treated using the ICH-CP combination in various concentrations. Methods: The viability of NB4 cells was evaluated by MTT assay, and their morphology of apoptosis was examined by fluorescence microscopy. Flow cytometry and Annexin V/PI staining were used to quantify apoptosis. Finally, the expression of three genes, Bax, Bcl-2, and Survivin was inquired by real-time PCR. Results: According to the results, ICH-CP was able to destroy about 60% of NB4 cells in a dose and time-dependent manner. Light microscopy and fluorescence microscopy studies on treated cells confirmed the induction of apoptosis. Also, the real-time PCR analysis showed that ICH-CP induces apoptosis in the NB4 cell line via the down-regulation of Survivin and Bcl-2, in contrast to the up-regulation of the Bax gene. Conclusion: Based on the present data, it seems that the novel compound can be a good candidate for the treatment of acute myeloid leukemia. Furthermore, it is recommended to evaluate the qualification of ICH-CP as an adjunctive agent for other cancer cell lines.

Effective anti-tumor immune responses are orchestrated by immune cell partnership network that functions through tissue homeostatic pathways, not direct cytotoxicity.

The liver hosts a diverse array of immune cells that play pivotal roles in both maintaining tissue homeostasis and responding to disease. However, the precise contributions of these immune cells in the progression of nonalcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC) remain unclear. Utilizing a systems immunology approach, we reveal that liver immune responses are governed by a dominant-subdominant hierarchy of ligand-receptor-mediated homeostatic pathways. In healthy individuals, inflammatory immune responses operate within these pathways, challenging the notion of the liver as a purely tolerogenic organ. Chronic consumption of a Western diet (WD) disrupts hepatocyte function and reconfigures immune interactions, resulting in hepatic stellate cells (HSCs), cancer cells, and NKT cells driving 80% of the immune activity during NAFLD. In HCC, 80% of immune response involves NKT cells and monocytes collaborating with hepatocytes and myofibroblasts to restore disrupted homeostasis. Interestingly, dietary correction during NAFLD yields nonlinear outcomes: tumor progression coincides with the failure of mounting homeostatic immune responses, whereas tumor prevention is associated with sustained immune responses, predominantly orchestrated by monocytes. These monocytes actively target fibroblasts and myofibroblasts, creating a tumor-suppressive microenvironment. Notably, only 5% of T cells displayed apoptosis-inducing activity, selectively contributing to the turnover of hepatic stromal cells, particularly myofibroblasts and fibroblasts. Our findings suggest that effective anti-tumor immune responses in the liver are primarily mediated by immune cells sustaining tissue homeostasis, rather than relying on direct cytotoxic mechanisms.

Comparison the impact of mesenchymal stromal cells, their microvesicles and plasma enriched with soluble platelet factors on survival and apoptosis of rat spleen lymphocytes <i>in vitro</i>

BACKGROUND: The trophic function is one of the important but insufficiently studied features of mesenchymal stromal cells (MSCs), their microvesicles (MVs), and plasma enriched with soluble platelet factors (PRPs), which ensure the viability of target cells. AIM: To analyze the capability of MSCs, MVs, and PRP to affect the viability and spontaneous and activation-induced apoptosis of rat spleen lymphocytes during culturing in vitro. MATERIALS AND METHODS: MSCs were isolated from the mononuclear cell fraction of the femoral bone marrow of Wistar rats using the plastic adhesion method. MVs were obtained from the conditioned medium of MSCs by centrifugation at 14,500 g. PRP was prepared by freezing/thawing rat peripheral blood platelet concentrate. Rat spleen lymphocytes were isolated on a density gradient of 1.077 g/cm3. The viability and degree of lymphocyte apoptosis in vitro were assessed by flow cytometry for 7-AAD incorporation and binding to annexin V. RESULTS: The presence of MSCs at 10 and 20% concentrations caused an increase in the number of living intact and PMA-activated lymphocytes by the end of 3-day in vitro cultivation. Compared with controls, the amount of necrotic cells decreased 8.3–13.5 times, and the number of apoptotic cells decreased 2.3–4.0 times, mainly due to lymphocytes at the late stage of apoptosis. MVs of MSCs at the indicated concentrations did not significantly affect the viability of lymphocytes cultured in vitro but reduced the level of apoptosis of intact and PMA-activated lymphocytes by 3.6 (р=0.03) and 4.8–5.2 (р=0.048; р=0.03) times respectively. Studies have shown that 1.25% rat PRP has a growth-stimulatory activity against MSCs but not against lymphocytes cultured in vitro. In the culture of intact lymphocytes, PRPs did not significantly affect cell viability with a slight decrease (2.7–2.9 fold, p 0.05) in the number of necrotic cells. In the culture of PMA-activated lymphocytes, 1.25–2.50% PRP increased the number of living cells by 1.6–2.2 times (р=0.002; р=0.01) and the number of necrotic cells by two times (р=0.02). CONCLUSION: MSCs, MVs of MSCs, and PRP, in decreasing order, enhanced the viability of rat spleen lymphocytes and suppressed late apoptosis during in vitro cultivation. Lymphocytes activated by phorbol myristate acetate are more sensitive to their vital action compared with resting cells.

Steroidal constituents in the whole plants of Helleborus niger and their cytotoxic activity in vitro

Phytochemical investigation of the whole plants of Helleborus niger L. (Ranunculaceae) resulted in the isolation of five undescribed compounds, including one bufadienolide (1), two bufadienolide rhamnosides (2 and 3), and two ecdysteroids (12 and 13), along with eight known compounds (4–11). The chemical structures of 1–3, 12, and 13 were determined by spectroscopic studies, including 2D NMR, and chromatographic and spectroscopic analyses of the hydrolyzed products. Compounds 1–13 were evaluated for their cytotoxic activity against HL-60 human leukemia cells, A549 human lung adenocarcinoma cells, SBC-3 human small-cell lung cancer cells, and TIG-3 human normal diploid lung cells. Compounds 1–12 showed cytotoxic activity against HL-60, A549, and SBC-3 cells, with IC50 values ranging from 0.0016 to 6.1 μM. Bufadienolide rhamnoside 2 exhibited potent cell proliferation inhibitory activity against SBC-3 cells after 24–48 h of treatment and apoptosis-inducing activity in SBC-3 cells via an intrinsic pathway after 72 h of treatment. The JFCR39 panel screening of 2 suggests that the molecular target of 2 is Na+,K+-ATPase.

Activation of Piezo1 by intracranial hypertension induced neuronal apoptosis via activating hippo pathway.

Most of the subarachnoid hemorrhage (SAH) patients experienced the symptom of severe headache caused by intracranial hypertension. Piezo1 is a mechanosensitive ion channel protein. This study aimed to investigate the effect of Piezo1 on neurons in response to intracranial hypertension. The SAH rat model was performed by the modified endovascular perforation method. Piezo1 inhibitor GsMTx4 was administered intraperitoneally after SAH induction. To investigate the underlying mechanism, the selective Piezo1 agonist Yoda1, Piezo1 shRNA, and MY-875 were administered via intracerebroventricular injection before SAH induction. Invitro, we designed a pressurizing device to exclusively explore the effect of Piezo1 activation on primary neurons. Neurons were pretreated with Piezo1 inhibition followed by intracranial hypertension treatment, and then apoptosis-related proteins were detected. Piezo1 inhibition significantly attenuated neuronal apoptosis and improved the outcome of neurological deficits in rats after SAH. The Hippo pathway agonist MY-875 reversed the anti-apoptotic effects of Piezo1 knockdown. Invitro, intracranial hypertension mimicked by the pressurizing device induced Piezo1 expression, resulting in Hippo pathway activation and neuronal apoptosis. The Hippo pathway inhibitor Xmu-mp-1 attenuated Yoda1-induced neuronal apoptosis. In addition, the combination of hypertension and oxyhemoglobin treatment exacerbated neuronal apoptosis. Intracranial hypertension induced Piezo1 expression, neuronal apoptosis, and the Hippo pathway activation; the Hippo signaling pathway is involved in Piezo1 activation-induced neuronal apoptosis in respond to intracranial hypertension. Primary neurons treated with intracranial hypertension and oxyhemoglobin together can better characterize the circumstance of SAH invivo, which is contributed to construct an ideal invitro SAH model.

TFEB activation hallmarks antigenic experience of B lymphocytes and directs germinal center fate decisions

Ligation of the B cell antigen receptor (BCR) initiates humoral immunity. However, BCR signaling without appropriate co-stimulation commits B cells to death rather than to differentiation into immune effector cells. How BCR activation depletes potentially autoreactive B cells while simultaneously primes for receiving rescue and differentiation signals from cognate T lymphocytes remains unknown. Here, we use a mass spectrometry-based proteomic approach to identify cytosolic/nuclear shuttling elements and uncover transcription factor EB (TFEB) as a central BCR-controlled rheostat that drives activation-induced apoptosis, and concurrently promotes the reception of co-stimulatory rescue signals by supporting B cell migration and antigen presentation. CD40 co-stimulation prevents TFEB-driven cell death, while enhancing and prolonging TFEB’s nuclear residency, which hallmarks antigenic experience also of memory B cells. In mice, TFEB shapes the transcriptional landscape of germinal center B cells. Within the germinal center, TFEB facilitates the dark zone entry of light-zone-residing centrocytes through regulation of chemokine receptors and, by balancing the expression of Bcl-2/BH3-only family members, integrates antigen-induced apoptosis with T cell-provided CD40 survival signals. Thus, TFEB reprograms antigen-primed germinal center B cells for cell fate decisions.

Biological Evaluation of Dinuclear Platinum(II) Complexes with Aromatic N-Heterocycles as Bridging Ligands.

The history of effective anti-cancer medications begins with the discovery of cisplatin's anti-cancer properties. Second-generation analogue, carboplatin, with a similar range of effectiveness, made progress in improving these drugs with fewer side effects and better solubility. Renewed interest in platinum-based drugs has been increasing in the past several years. These developments highlight a revitalized enthusiasm and ongoing exploration in platinum chemotherapy based on the series of dinuclear platinum(II) complexes, [{Pt(L)Cl}2(μ-bridging ligand)]2+, which have been synthesized and evaluated for their biological activities. These complexes are designed to target various cancerous conditions, exhibiting promising antitumor, antiproliferative, and apoptosis-inducing activities. The current work aims to shed light on the potential of these complexes as next-generation platinum-based therapies, highlighting their enhanced efficacy and reduced side effects, which could revolutionize the approach to chemotherapy.

Cytotoxicity and apoptosis activities of passion fruit (Passiflora edulis Sims) seed extract on HSC-2, HSC-3, MCF-7, and HaCaT cell lines

Context: Passion fruit (Passiflora edulis Sims) is a well-known plant in the tropical islands, especially in North Sumatra, Indonesia, because of its sweet and refreshing taste. Although the fruit is often used as a syrup and sweetener, the efficacy of P. edulis fruit seed extract for anticancer activity has not been widely studied. Aims: To evaluate the ability of P. edulis fruit seed extract to induce cytotoxicity and apoptosis in HSC-2, HSC-3, MCF-7, and HaCaT cell lines. Methods: P. edulis fruit seed extract was extracted by using 96% ethanol. The cytotoxicity activity was measured by using an MTT assay for 48 hours. Apoptosis was examined using a TUNEL assay, and the morphology of the apoptosis bodies was analyzed using electron microscopy. Results: The IC50 values of P. edulis fruit seed extract were 572.79 µg/mL and 439.54 µg/mL for HSC-3 and MCF-7, respectively. The seed did not show cytotoxic activity on the HSC-2 cell line, but it induced proliferation of the HaCaT cell line in the maximum dose. The P. edulis fruit seed extract induced apoptosis activity in HSC-3, MCF-7, and HaCaT cell lines. Most DNA fragments were found in the cytosol of HSC-3 cells and the nucleus of MCF-7 cells. Conclusions: The P. edulis fruit seed extract has cytotoxicity and apoptosis activities in oral cancer (HSC-3 cells) and breast cancer (MCF-7 cells), as well as being safe in normal human keratinocytes (HaCaT cell line). The P. edulis fruit seed extract can be considered an adjuvant agent in cancer treatment.

Quantification of collective signalling in time-lapse microscopy images.

Live-cell imaging of fluorescent biosensors has demonstrated that space-time correlations in signalling of cell collectives play an important organisational role in morphogenesis, wound healing, regeneration, and maintaining epithelial homeostasis. Here, we demonstrate how to quantify one such phenomenon, namely apoptosis-induced ERK activity waves in the MCF10A epithelium. We present a protocol that starts from raw time-lapse fluorescence microscopy images and, through a sequence of image manipulations, ends with ARCOS, our computational method to detect and quantify collective signalling. We also describe the same workflow in the interactive napari image viewer to quantify collective phenomena for users without prior programming experience. Our approach can be applied to space-time correlations in cells, cell collectives, or communities of multicellular organisms, in 2D and 3D geometries.

Anticancer activity of the ethylacetate fraction of Vernonia amygdalina Delile towards overexpression of HER-2 breast cancer cell lines

Vernonia amygdalina Delile, coming from the Asteraceae tribe, contains active compounds that can treat breast cancer. This study examines the anticancer activity of Vernonia amygdalina Delile leaves, an active fraction of MCF-7/HER-2 breast cancer cells. Thin-layer chromatography determines the phytochemical screening. Cytotoxic and proliferation analyses were determined using the MTT method for the MCF-7/HER-2 breast cancer cell line. The cell cycle and apoptosis profiles were examined using flow cytometry. The results can be summarized in this study: Vernonia amygdalina Delile fraction contains a flavonoid with great potential for pharmacological activities, for instance, inhibiting the growth of cancer cells. The ethyl acetate fraction was more potent and cytotoxic on MCF-7/HER-2 cells (IC50 = 66 μg/mL) than extract ethanol (IC50 = 130 μg/mL). The ethylacetate fraction of Vernonia amygdalina Delile has been proven to inhibit cell proliferation by decreasing cell viability with an IC50 of 66 μg/mL concentration incubated for 24, 48, and 72 hrs with cell viability values of 64.46%, 61.67%, and 53.89%, respectively, compared to the ethanol extract IC50 of 130 μg/mL concentration with cell viability values of 56.0%, 50.19%, and 58.67%, respectively, which induced apoptosis and inhibited the cell cycle in the G2-M phase. To conclude, the ethyl acetate fraction of Vernonia amygdalina Delile can be used as an anticancer against the MCF-7/HER-2 cell line with an IC50 of 66 μg/mL, inhibiting cell proliferation and the cell cycle and inducing apoptosis activity in the MCF-7/HER-2 cell.

PEG-lipid-modified agonistic antibody against tumor necrosis factor receptor family elicits superior apoptosis-inducing activity against human carcinoma

We have recently developed a novel PEG-lipid-modified antibody to enhance the induction of apoptosis by the agonistic antibody. The chemically modified TRA-8 antibody [anti-death receptor 5 (DR5) antibody] with PEG-lipid (DSPE-PEG) demonstrated significant cytotoxic activity in vitro without the need for crosslinking with a secondary antibody, which is typically required. We investigated the correlation between the PEG-lipid structure and the cytotoxic activity of the modified antibodies by varying the PEG length or lipid structure. However, when the DSPE-PEG-modified TRA-8 antibody was incubated with plasma, it lost its cytotoxic activity, likely due to degradation in the DSPE-PEG component. Nevertheless, by designing new PEG-lipids that are intended to be resistant to enzymatic degradation, we were able to prevent this degradation and restore the cytotoxic activity of the modified antibody. These findings provide valuable insights for the design of PEG-lipid-modified antibodies and suggest their potential effectiveness in enhancing cancer therapy.

Harnessing molecular hybridization approach to discover novel quinoline EGFR-TK inhibitors for cancer treatment.

Aim: Using molecular hybridization approach, novel 18 quinoline derivatives (6a-11) were designed and synthesized as EGFR-TK inhibitors. Materials & methods: The antiproliferative activity was assessed against breast (MCF-7), leukemia (HL-60) and lung (A549) cancer cell lines. Moreover, the most active quinoline derivatives (6d and 8b) were further investigated for their potential as EGFR-TK inhibitors. In addition, cell cycle analysis and apoptosis induction activity were conducted. Results: A considerable cytotoxic activity was attained with IC50 values spanning from 0.06 to 1.12μM. Besides, the quinoline derivatives 6d and 8b displayed potent inhibitory activity against EFGR with IC50 values of 0.18 and 0.08μM, respectively. Conclusion: Accordingly, the afforded quinoline derivatives can be used as promising lead anticancer candidates for future optimization.

Cytotoxic and Apoptosis-Inducing Activities of Iridium Complexes Bearing 2-Phenylimidazo[4,5-f][1,10]-Phenanthroline Derivatives in Human Cancer Cells

Cytotoxic and Apoptosis-Inducing Activities of Iridium Complexes Bearing 2-Phenylimidazo[4,5-f][1,10]-Phenanthroline Derivatives in Human Cancer Cells

New Polyether Macrocycles as Promising Antitumor Agents-Targeted Synthesis and Induction of Mitochondrial Apoptosis.

A series of previously unknown aromatic polyether macrodiolides containing a cis,cis-1,5-diene moiety in the molecule were synthesized in 47-74% yields. Macrocycle compounds were first obtained by intermolecular esterification of aromatic polyether diols with α,ω-alka-nZ,(n+4)Z-dienedioic acids mediated by N-(3-(dimethylamino)propyl)-N'-ethylcarbodiimide hydrochloride (EDC·HCl) and 4-(dimethylamino)pyridine (DMAP). For the synthesized compounds, studies of cytotoxicity on tumor (Jurkat, K562, U937), conditionally normal (HEK293) cell lines, and normal fibroblasts were carried out. CC50 was determined, and the therapeutic selectivity index of cytotoxic action (SI) in comparison with normal fibroblasts was evaluated. With the involvement of modern methods of flow cytometry for the most promising macrocycles, their effect on mitochondria and the cell cycle was investigated. It was found that a new macrocycle exhibits pronounced apoptosis-inducing activity toward Jurkat cells and can retard cell division by blocking at the G1/S checkpoint. Also, it was shown that the synthesized macrodiolides influence mitochondria due to their high ability to penetrate the mitochondrial membrane.

A drug repurposing approach of Atorvastatin calcium for its antiproliferative activity for effective treatment of breast cancer: In vitro and in vivo assessment

Breast cancer, the most common cancer among women, caused over 500,000 deaths in 2020. Conventional treatments are expensive and have severe side effects. Drug repurposing is a novel approach aiming to reposition clinically approved non-cancer drugs into newer cancer treatments. Atorvastatin calcium (ATR Ca) which is used for the treatment of hypercholesterolemia has potential to modulate cell growth and apoptosis. The study aimed at utilizing gelucire-based solid lipid nanoparticles (SLNs) and lactoferrin (Lf) as targeting ligand to enhance tumor targeting of atorvastatin calcium for effective management of breast cancer. Lf-decorated-ATR Ca-SLNs showed acceptable particle size and PDI values <200 nm and 0.35 respectively, entrapment efficiency >90% and sustained drug release profile with 78.97 ± 12.3% released after 24 h. In vitro cytotoxicity study on breast cancer cell lines (MCF-7) showed that Lf-decorated-ATR Ca-SLNs obviously improved anti-tumor activity by 2 to 2.5 folds compared to undecorated ATR Ca-SLNs and free drug. Further, In vivo study was also carried out using Ehrlich breast cancer model in mice. Caspase-3 apoptotic marker revealed superior antineoplastic and apoptosis-inducing activity in the groups treated with ATR Ca-SLNs either decorated/ undecorated with Lf in dosage 10 mg/kg/day p < 0.001 with superior activity for lactoferrin-decorated formulation.

RETRACTED: Alhakamy et al. Optimized Icariin Phytosomes Exhibit Enhanced Cytotoxicity and Apoptosis-Inducing Activities in Ovarian Cancer Cells. Pharmaceutics 2020, 12, 346.

The journal retracts the article, "Optimized Icariin Phytosomes Exhibit Enhanced Cytotoxicity and Apoptosis-Inducing Activities in Ovarian Cancer Cells" [...].

Gaillardin inhibits autophagy and induces apoptosis in MCF-7 breast cancer cells by regulating JAK/STAT pathway.

Gaillardin is a potent anti-cancer sesquiterpene lactone found in Inula oculus-christi. The present study examined the effects of gaillardin on apoptosis and autophagy in the MCF-7 breast cancer cell line. The MTT assay was used to unravel the antiproliferative effects of gaillardin on MCF-7 cells. The expression of apoptosis-related genes including CASP3, BAX, BCL2, STAT3, and JAK2, and key markers of autophagy such as ATG1, ATG4, ATG5, ATG7, ATG12, BECN1, and MAP1LC3A were measured by real time-PCR method. The protein expression of Caspase 3, phosphorylated JAK2, phosphorylated STAT3, ATG1, ATG4, ATG5, ATG12, Beclin1, and LC-III was determined using western blotting. Gaillardin treatment significantly decreased the proliferation of MCF-7 cells with a parallel upregulation of the level of pro-apoptotic caspase-3 enzyme with no effect on Bax and Bcl2 expression. The levels of phosphorylated and active forms of JAK2 and STAT3 proteins were reduced following the treatment of MCF-7 cells with gaillardin. This sesquiterpene lactone com-pound considerably downregulated the levels of six autophagy markers, including ATG1, ATG4, ATG5, ATG12, Beclin1, and LC-III in MCF-7 cells. These data indicated the apoptosis-inducing activity of gaillardin in MCF-7 cells by a mechanism that inhibits the JAK/STAT signaling pathway. Further, autophagy inhibition was the other phenomenon caused by gaillardin in MCF-7 cells. These results can provide evidence to highlight the role of gaillardin as a novel therapeutic for the treatment of breast cancer.

Benzothiazole-based apoptosis inducers: A comprehensive overview and future prospective.

Cancer has become a major concern in healthcare globally, and over time, incidences and prevalence of cancer are increasing. To counter this, a lot of anticancer drugs are approved and are in clinical use, playing a pivotal role in its treatment. Due to drug resistance and adverse effects, a continuous demand for novel, potent, and safe candidates to treat cancer is always there. Over the last few decades, various heterocyclic ring-based derivatives have been explored and reported in the literature. In this regard, benzothiazole scaffold-based compound emerged as the versatile ring for developing novel and safe anticancer candidates. In this article, we have reported various benzothiazole heterocyclic ring-based derivatives demonstrating potent antiproliferative activity by induction of apoptosis via an intrinsic pathway in a dose-dependent manner. These compounds also displayed inhibition of different enzymes, for example, Aurora kinase, epidermal growth factor receptor, vascular endothelial growth factor receptor, phosphoinositide kinases, DNA topoisomerase, and tubulin polymerases. This study focused on a comprehensive overview of antiproliferative activity, structure-activity relationship, apoptosis induction activity, and enzyme inhibition by benzothiazole-based compounds.