Drug Repurposing of Selected Antibiotics: An Emerging Approach in Cancer Drug Discovery.

Drug repurposing is a method of investigating new therapeutic applications for previously approved medications. This repurposing approach to "old" medications is now highly efficient, simple to arrange, and cost-effective and poses little risk of failure in treating a variety of disorders, including cancer. Drug repurposing for cancer therapy is currently a key topic of study. It is a way of exploring recent therapeutic applications for already-existing drugs. Theoretically, the repurposing strategy has various advantages over the recognized challenges of creating new molecular entities, including being faster, safer, easier, and less expensive. In the real world, several medications have been repurposed, including aspirin, metformin, and chloroquine. However, doctors and scientists address numerous challenges when repurposing drugs, such as the fact that most drugs are not cost-effective and are resistant to bacteria. So the goal of this review is to gather information regarding repurposing pharmaceuticals to make them more cost-effective and harder for bacteria to resist. Cancer patients are more susceptible to bacterial infections. Due to their weak immune systems, antibiotics help protect them from a variety of infectious diseases. Although antibiotics are not immune boosters, they do benefit the defense system by killing bacteria and slowing the growth of cancer cells. Their use also increases the therapeutic efficacy and helps avoid recurrence. Of late, antibiotics have been repurposed as potent anticancer agents because of the evolutionary relationship between the prokaryotic genome and mitochondrial DNA of eukaryotes. Anticancer antibiotics that prevent cancer cells from growing by interfering with their DNA and blocking growth of promoters, which include anthracyclines, daunorubicin, epirubicin, mitoxantrone, doxorubicin, and idarubicin, are another type of FDA-approved antibiotics used to treat cancer. According to the endosymbiotic hypothesis, prokaryotes and eukaryotes are thought to have an evolutionary relationship. Hence, in this study, we are trying to explore antibiotics that are necessary for treating diseases, including cancer, helping people reduce deaths associated with various infections, and substantially extending people's life expectancy and quality of life.

Exploiting transcription factors to target EMT and cancer stem cells for tumor modulation and therapy.

Transcription factors (TFs) are essential in controlling gene regulatory networks that determine cellular fate during embryogenesis and tumor development. TFs are the major players in promoting cancer stemness by regulating the function of cancer stem cells (CSCs). Understanding how TFs interact with their downstream targets for determining cell fate during embryogenesis and tumor development is a critical area of research. CSCs are increasingly recognized for their significance in tumorigenesis and patient prognosis, as they play a significant role in cancer initiation, progression, metastasis, and treatment resistance. However, traditional therapies have limited effectiveness in eliminating this subset of cells, allowing CSCs to persist and potentially form secondary tumors. Recent studies have revealed that cancer cells and tumors with CSC-like features also exhibit genes related to the epithelial-to-mesenchymal transition (EMT). EMT-associated transcription factors (EMT-TFs) like TWIST and Snail/Slug can upregulate EMT-related genes and reprogram cancer cells into a stem-like phenotype. Importantly, the regulation of EMT-TFs, particularly through post-translational modifications (PTMs), plays a significant role in cancer metastasis and the acquisition of stem cell-like features. PTMs, including phosphorylation, ubiquitination, and SUMOylation, can alter the stability, localization, and activity of EMT-TFs, thereby modulating their ability to drive EMT and stemness properties in cancer cells. Although targeting EMT-TFs holds potential in tackling CSCs, current pharmacological approaches to do so directly are unavailable. Therefore, this review aims to explore the role of EMT- and CSC-TFs, their connection and impact in cellular development and cancer, emphasizing the potential of TF networks as targets for therapeutic intervention.

Flavonoid Myricetin as Potent Anticancer Agent: A Possibility towards Development of Potential Anticancer Nutraceuticals.

Good nutrition plays a crucial role in maintaining a balanced lifestyle. The beneficial effects of nutrition have been found to counteract nutritional disturbances with the expanded use of nutraceuticals to treat and manage cardiovascular diseases, cancer, and other developmental defects over the last decade. Flavonoids are found abundantly in plant-derived foods such as fruits, vegetables, tea, cocoa, and wine. Fruits and vegetables contain phytochemicals like flavonoids, phenolics, alkaloids, saponins, and terpenoids. Flavonoids can act as anti-inflammatory, anti-allergic, anti-microbial (antibacterial, antifungal, and antiviral) antioxidant, anti-cancer, and anti-diarrheal agents. Flavonoids are also reported to upregulate apoptotic activity in several cancers such as hepatic, pancreatic, breast, esophageal, and colon. Myricetin is a flavonol which is naturally present in fruits and vegetables and has shown possible nutraceutical value. Myricetin has been portrayed as a potent nutraceutical that may protect against cancer. The focus of the present review is to present an updated account of studies demonstrating the anticancer potential of myricetin and the molecular mechanisms involved therein. A better understanding of the molecular mechanism(s) underlying its anticancer activity would eventually help in its development as a novel anticancer nutraceutical having minimal side effects.

Targeted Inhibition of Hsp90 in Combination with Metformin Modulates Programmed Cell Death Pathways in A549 Lung Cancer Cells.

The pathophysiology of lung cancer is dependent on the dysregulation in the apoptotic and autophagic pathways. The intricate link between apoptosis and autophagy through shared signaling pathways complicates our understanding of how lung cancer pathophysiology is regulated. As drug resistance is the primary reason behind treatment failure, it is crucial to understand how cancer cells may respond to different therapies and integrate crosstalk between apoptosis and autophagy in response to them, leading to cell death or survival. Thus, in this study, we have tried to evaluate the crosstalk between autophagy and apoptosis in A549 lung cancer cell line that could be modulated by employing a combination therapy of metformin (6 mM), an anti-diabetic drug, with gedunin (12 µM), an Hsp90 inhibitor, to provide insights into the development of new cancer therapeutics. Our results demonstrated that metformin and gedunin were cytotoxic to A549 lung cancer cells. Combination of metformin and gedunin generated ROS and promoted MMP loss and DNA damage. The combination further increased the expression of AMPKα1 and promoted the nuclear localization of AMPKα1/α2. The expression of Hsp90 was downregulated, further decreasing the expression of its clients, EGFR, PIK3CA, AKT1, and AKT3. Inhibition of the EGFR/PI3K/AKT pathway upregulated TP53 and inhibited autophagy. The combination was promoting nuclear localization of p53; however, some cytoplasmic signals were also detected. Further increase in the expression of caspase 9 and caspase 3 was observed. Thus, we concluded that the combination of metformin and gedunin upregulates apoptosis by inhibiting the EGFR/PI3K/AKT pathway and autophagy in A549 lung cancer cells.

Untangling the complexity of heat shock protein 27 in cancer and metastasis.

Heat shock protein 27 is a type of molecular chaperone whose expression gets up-regulated due to reaction towards different stressful triggers including anticancer treatments. It is known to be a major player of resistance development in cancer cells, whereby cells are sheltered against the therapeutics that normally activate apoptosis. Heat shock protein 27 (HSP27) is one of the highly expressed proteins during various cellular insults and is a strong tumor survival factor. HSP27 influences various cellular pathways associated with cancer cell survival and growth such as apoptosis, autophagy, metastasis, angiogenesis, epithelial to mesenchymal transition, etc. HSP27 is molecular machinery which prevents the clumping of numerous substrates or client proteins which get mutated in cancer. It has been reported in several studies that targeting HSP27 is difficult because of its dynamic structure and absence of an ATP-binding site. Here, in this review, we have summarized different modulators of HSP27 and their mechanism of action as well. Effect of deregulated HSP27 in various cancer models, limitations of targeting HSP27, resistance against the conventional drugs generated due to the overexpression of HSP27, and measures to counteract this effect have also been discussed here in detail.

Molecular chaperones in DNA repair mechanisms: Role in genomic instability and proteostasis in cancer.

Cells are exposed to several environmental or chemical stressors that may cause DNA damage. DNA damage alters the normal functioning of the cell and contributes to several diseases, including cancer. Cells either induce DNA damage repair pathways or programmed cell death pathways to prevent disease formation depending on the severity of the stress and the damage caused. The DNA repair mechanisms are crucial to maintaining genome stability. During this adaptive response, the heat shock proteins (HSPs) are the key players. HSPs are overexpressed during genotoxic stress, but the role of different molecular players in the interaction between HSPs and DNA repair proteins is still poorly understood. As DNA damage promotes genomic instability and proteotoxic stress, modulating the protein quality control systems like the HSPs network could be a promising strategy for targeting disease pathologies associated with genomic instability, such as cancer. Hence, this review highlights the role of HSPs in DNA repair pathways. Further, the review also provides an outlook on the role of genomic instability and protein homeostasis in cancer, which is crucial to understanding the mechanisms behind its survival and developing novel targeted therapies.

Crosstalk Between ROS and Autophagy in Tumorigenesis: Understanding the Multifaceted Paradox.

Cancer formation is a highly regulated and complex process, largely dependent on its microenvironment. This complexity highlights the need for developing novel target-based therapies depending on cancer phenotype and genotype. Autophagy, a catabolic process, removes damaged and defective cellular materials through lysosomes. It is activated in response to stress conditions such as nutrient deprivation, hypoxia, and oxidative stress. Oxidative stress is induced by excess reactive oxygen species (ROS) that are multifaceted molecules that drive several pathophysiological conditions, including cancer. Moreover, autophagy also plays a dual role, initially inhibiting tumor formation but promoting tumor progression during advanced stages. Mounting evidence has suggested an intricate crosstalk between autophagy and ROS where they can either suppress cancer formation or promote disease etiology. This review highlights the regulatory roles of autophagy and ROS from tumor induction to metastasis. We also discuss the therapeutic strategies that have been devised so far to combat cancer. Based on the review, we finally present some gap areas that could be targeted and may provide a basis for cancer suppression.

Dietary factors and SARS-CoV-2 contagion: in silico studies on modulation of viral and host proteins by spice actives.

The SARS-CoV-2 contagion has had a huge impact on world population. It has been observed that despite massive spread of the contagion in India particularly during the second wave, the overall case fatality rates remain low. This prompted us to look into dietary factors that can possibly modulate the viral impact and/or host response. In silico studies were carried out on forty-two commonly used spices and their 637 known active compounds with an aim of identifying such compounds that may have propensity to reduce viral impact or boost host immune response. We chose to study SARS-Cov-2 helicase on account of its functional importance in maintaining viral load within the host, and the human tank binding protein (TBK1) for its important role in host immunity. We carried out in silico virtual screening, docking studies with 637 phytochemical against these two proteins, using in silico methods. Upon assessing the strength of the ligand-target interactions and post simulation binding energy profile, our study identifies procyanidin-B4 from bay leaf, fenugreekine from fenugreek seed and gallotannin from pomegranate seed as active interactors that docked to viral helicase. Similarly, we identified eruboside B from garlic, gallotannin from pomegranate seed, as strong interacting partners to human TBK1. Our studies thus present dietary spice constituents as potential protagonists for further experimentation to understand how spices in the diet might help the hosts in countering the viral assault and mount a robust protective response against COVID and other infections.Communicated by Ramaswamy H. Sarma.

Probing the Structure-Function relationship and amyloidogenic propensities in natural variants of apolipoprotein A-I.

BACKGROUND: Apolipoprotein A-I (apoA-I) protects against atherosclerosis and participates in the removal of excess cellular cholesterol from peripheral organs. Several naturally occurring apoA-I mutations are associated with familial systemic amyloidosis, with deposition of amyloid aggregates in peripheral organs, resulting in multiple organ failure. Systematic studies on naturally occurring variants are needed to delineate their roles and involvement in pathogenesis. METHODS: We performed a comparative structure-function analysis of five naturally occurring apoA-I variants and the wild-type protein. Circular dichroism, Fourier-transform infrared spectroscopy, thioflavin T and congo red fluorescence assays, thermal, chemical, and proteolytic stability assays, and 1,2-Dimyristoyl-sn-glycero-3-phosphocholine clearance analyses were used to assess the effects of mutations on the structure, function, stability, aggregation, and proteolytic susceptibility of the proteins to explore the mechanisms underlying amyloidosis and hypercholesterolemia. RESULTS: We observed structural changes in the mutants independent of fibril formation, suggesting the influence of the surrounding environment. The mutants were involved in aggregate formation to varying degree; L170P, R173P, and V156E showed an increased propensity to aggregate under different physiological conditions. ß sheet formation indicates that L170P and R173P participate in amyloid formation. Compared to WT, V156E and L170P exhibited higher capacity for lipid clearance. CONCLUSIONS: The selected point mutations, including those outside the hot spot regions of apoA-I structure, perturb the physiochemical and conformational behavior of the protein, influencing its function. GENERAL SIGNIFICANCE: The study provides insights into the structure-function relationships of naturally occurring apoA-I variants outside the hot spot mutation sites.

Hsp90 inhibitor gedunin causes apoptosis in A549 lung cancer cells by disrupting Hsp90:Beclin-1:Bcl-2 interaction and downregulating autophagy.

AIMS: Hsp90 is regarded as an important therapeutic target in cancer treatment. Client proteins of Hsp90 like Beclin-1, PI3K, and AKT, are associated with tumor development, poor prognosis, and resistance to cancer therapies. This study aims to analyze the role of Gedunin, an Hsp-90 inhibitor, in mediation of crosstalk between apoptosis and autophagy by targeting Beclin-1:Bcl-2 interaction, and ER stress. MAIN METHODS: A549 cells were treated with different concentrations of gedunin, and inhibitory rate was evaluated by MTT assay. Effect of gedunin on generation of reactive oxygen species, mitochondrial membrane potential, and chromatin condensation was studied by staining methods like DCFH-DA, MitoTracker, and DAPI. Expression of EGFR, PIK3CA, AKT, marker genes for apoptosis and autophagy were studied using semi-quantitative RT-PCR. Interaction study of Hsp90:Beclin-1:Bcl-2 was done by immunoprecipitation analysis. Protein expression of autophagy and apoptosis markers along with Grp78, Hsp70, and Hsp90 was analyzed by immunoblotting. KEY FINDINGS: Gedunin exerts cytotoxic effects, causes increase in ROS generation, downregulates mitochondrial membrane potential and induces loss in DNA integrity. mRNA expression analysis revealed that gedunin sensitized A549 cells towards apoptosis by downregulating EGFR, PIK3CA, AKT, and autophagy. Gedunin also inhibited interaction between Hsp90:Beclin-1:Bcl-2, leading to downregulation of autophagy (Beclin-1, Atg5-12 complex, and LC3) and antiapoptotic protein Bcl-2, which may result in ER stress-induced apoptosis. Moreover, Hsp90 inhibition by gedunin did not cause upregulation of Hsp70 expression. SIGNIFICANCE: Gedunin induces apoptosis in lung cancer cells by disrupting Hsp90:Beclin-1:Bcl-2 interaction and autophagy downregulation, thus making gedunin a good drug lead for targeting lung cancer.

Advanced glycation end products (AGEs), protein aggregation and their cross talk: new insight in tumorigenesis.

Protein glycation and protein aggregation are two distinct phenomena being observed in cancer cells as factors promoting cancer cell viability. Protein aggregation is an abnormal interaction between proteins caused as a result of structural changes in them after any mutation or environmental assault. Protein aggregation is usually associated with neurodegenerative diseases like Alzheimer's and Parkinson's, but of late, research findings have shown its association with the development of different cancers like lung, breast and ovarian cancer. On the contrary, protein glycation is a cascade of irreversible nonenzymatic reaction of reducing sugar with the amino group of the protein resulting in the modification of protein structure and formation of advanced glycation end products (AGEs). These AGEs are reported to obstruct the normal function of proteins. Lately, it has been reported that protein aggregation occurs as a result of AGEs. This aggregation of protein promotes the transformation of healthy cells to neoplasia leading to tumorigenesis. In this review, we underline the current knowledge of protein aggregation and glycation along with the cross talk between the two, which may eventually lead to the development of cancer.

Hydroxyl Group Difference between Anthraquinone Derivatives Regulate Different Cell Death Pathways via Nucleo-Cytoplasmic Shuttling of p53.

BACKGROUND: Despite a number of measures having been taken for cancer management, it is still the second leading cause of death worldwide. p53 is the protein principally being targeted for cancer treatment. Targeting p53 localization may be an effective strategy in chemotherapy as it controls major cell death pathways based on its cellular localization. Anthraquinones are bioactive compounds widely being considered as potential anticancer agents but their mechanism of action is yet to be explored. It has been shown that the number and position of hydroxyl groups within the different anthraquinones like Emodin and Chrysophanol reflects the number of intermolecular hydrogen bonds which affect its activity. Emodin contains an additional OH group at C-3, in comparison to Chrysophanol and may differentially regulate different cell death pathways in cancer cell. OBJECTIVE: The present study was aimed to investigate the effect of two anthraquinones Emodin and Chrysophanol on induction of different cell death pathways in human lung cancer cells (A549 cell line) and whether single OH group difference between these compounds differentially regulate cell death pathways. METHODS: The cytotoxic effect of Emodin and Chrysophanol was determined by the MTT assay. The expression of autophagy and apoptosis marker genes at mRNA and protein level after treatment was checked by the RT-PCR and Western Blot, respectively. For cellular localization of p53 after treatment, we performed immunofluorescence microscopy. RESULTS: We observed that both compounds depicted a dose-dependent cytotoxic response in A549 cells which was in concurrence with the markers associated with oxidative stress such as an increase in ROS generation, decrease in MMP and DNA damage. We also observed that both compounds up-regulated the p53 expression where Emodin causes nuclear p53 localization, which leads to down-regulation in mTOR expression and induces autophagy while Chrysophanol inhibits p53 translocation into nucleus, up-regulates mTOR expression and inhibits autophagy. CONCLUSION: From this study, it may be concluded that the structural difference of single hydroxyl group may switch the mechanism from one pathway to another which could be useful in the future to improve anticancer treatment and help in the development of new selective therapies.

Blocking mutation independent p53 aggregation by emodin modulates autophagic cell death pathway in lung cancer.

Loss of p53 function via mutation is a very common cause of human cancers. Recent studies have provided evidence on presence of self aggregated p53 in cancer cells leading to its altered functions towards cause of cancer. The general notion has been that mutated p53 exposes adhesive sites that promote self aggregation, however a complete mechanistic understanding to this has been lacking. We embarked on the present study towards exploring the differential aggregation pattern in cells expressing mutated TP53 (HaCaT keratinocytes) vs those expressing the wild type copy of the p53 protein (A549 lung cancer cell line). The studies led us to interesting observation that formation of p53 protein aggregates is not always associated with TP53 mutation. The A549 lung cancer cells, having wild type TP53, showed the appearance of p53 protein aggregates, while no protein aggregates were observed in normal HaCaT keratinocytes carrying mutant TP53. We went on to study the effect of blocking protein aggregation by emodin (1,3,8-trihydroxy-6-methyl-anthraquinone) and figured that inhibiting p53 protein aggregation can elevate the level of autophagy in A549 lung cancer cell line while there is no significant effect on autophagy in normal non-cancerous HaCaT cells. Moreover, ATG5 was found to be coaggregated with p53 aggregates which dissociated after emodin treatment, indicating further induction of autophagy in A549 cells only. From these observations, we conclude that the increased level of autophagy might be the mechanism for the removal of p53 protein aggregates which restores p53 function in A549 cells after emodin treatment .This encourages further studies towards deciphering related mechanistic aspects vis-à-vis potential therapeutic strategies against cancer.

ER chaperone GRP78 regulates autophagy by modulation of p53 localization.

GRP78 (glucose regulated protein 78) is a major Endoplasmic Reticulum (ER) chaperone that plays a pivotal role in normal ER functioning. Its increased expression also works as an indicator of ER stress. Its anti-apoptotic and pro-autophagic activity makes it an intriguing target to study the relationship between GRP78 and p53, which is also a major regulator of apoptosis and autophagy. Here, we studied the effect of Rotenone and Parathion on human lung cancer cells (A549 cell line) specifically with respect to ER stress and its association with different cell death pathways. In our study, we observed that both compounds increase reactive oxygen species (ROS) generation, down regulate mitochondrial membrane potential (MMP) and affect DNA integrity. Our results indicate that Parathion causes ER stress, up regulates the expression of GRP78, leads to nuclear localization of p53 and induces autophagy while Rotenone down regulates GRP78, causes cytoplasmic localization of p53 and inhibits autophagy. Therefore, it may be concluded that GRP78 affects p53 localization which in turn regulates autophagy.

Nexrutine inhibits azoxymethane-induced colonic aberrant crypt formation in rat colon and induced apoptotic cell death in colon adenocarcinoma cells.

Colon cancer is the third most common cause of death in the United States. Therefore, new preventive strategies are warranted for preventing colon cancer. Nexrutine (NX), an herbal extract from Phellodendron amurense, has been shown to have anti-inflammatory, anti-microbial and anti-cancer activity for various tissue specific cancers, but its chemopreventive efficacy has not been evaluated against colon cancer. Here, we explored the mechanism of chemopreventive/chemotherapeutic efficacy of NX against colon cancer. We found that dietary exposure of NX significantly reduced the number of azoxymethane (AOM)-induced aberrant crypt foci (ACF) in rats. In addition, significant inhibition in AOM-induced cell proliferation and reduced expression of the inflammatory markers COX-2, iNOS as well as the proliferative markers PCNA and cyclin D1 were also seen. Moreover, NX exposure significantly enhanced apoptosis in the colon of AOM treated rats. Furthermore, in in vitro studies, NX (2.5, 5, 10 µg/ml, 48 h) decreased cell survival and colony formation while inducing G0/G1 cell cycle arrest and apoptosis in colon adenocarcinoma cells COLO205 and HCT-15. However, NX had minimal cytotoxic effect on IEC-6 normal rat intestinal cells, suggesting its high therapeutic index. NX treatment also modulates the level of Bax and Bcl-2 proteins along with cytochrome c release, cleavage and enhanced expression of poly (adenosine diphosphate-ribose) polymerase as well as the catalytic activity of caspase 3 and caspase 9 in both COLO205 and HCT-15 cells. Based on these in vivo and in vitro findings, we suggest that NX could be useful candidate agent for colon cancer chemoprevention and treatment. © 2015 Wiley Periodicals, Inc.

The Chromone Alkaloid, Rohitukine, Affords Anti-Cancer Activity via Modulating Apoptosis Pathways in A549 Cell Line and Yeast Mitogen Activated Protein Kinase (MAPK) Pathway.

The field of cancer research and treatment has made significant progress, yet we are far from having completely safe, efficient and specific therapies that target cancer cells and spare the healthy tissues. Natural compounds may reduce the problems related to cancer treatment. Currently, many plant products are being used to treat cancer. In this study, Rohitukine, a natural occurring chromone alkaloid extracted from Dysoxylum binectariferum, was investigated for cytotoxic properties against budding yeast as well as against lung cancer (A549) cells. We endeavored to specifically study Rohitukine in S. cerevisiae in the context of MAPK pathways as yeast probably represents the experimental model where the organization and regulation of MAPK pathways are best understood. MAPK are evolutionarily conserved protein kinases that transfer extracellular signals to the machinery controlling essential cellular processes like growth, migration, differentiation, cell division and apoptosis. We aimed at carrying out hypothesis driven studies towards targeting the important network of cellular communication, a critical process that gets awry in cancer. Employing mutant strains of genetic model system Saccharomyces cerevisiae. S. cerevisiae encodes five MAPKs involved in control of distinct cellular responses such as growth, differentiation, migration and apoptosis. Our study involves gene knockouts of Slt2 and Hog1 which are functional homologs of human ERK5 and mammalian p38 MAPK, respectively. We performed cytotoxicity assay to evaluate the effect of Rohitukine on cell viability and also determined the effects of drug on generation of reactive oxygen species, induction of apoptosis and expression of Slt2 and Hog1 gene at mRNA level in the presence of drug. The results of this study show a differential effect in the activity of drug between the WT, Slt2 and Hog1 gene deletion strain indicating involvement of MAPK pathway. Further, we investigated Rohitukine induced cytotoxic effects in lung cancer cells and stimulated the productions of ROS after exposure for 24 hrs. Results from western blotting suggest that Rohitukine triggered apoptosis in A549 cell line through upregulation of p53, caspase9 and down regulation of Bcl-2 protein. The scope of this study is to understand the mechanism of anticancer activity of Rohitukine to increase the repertoire of anticancer drugs, so that problem created by emergence of resistance towards standard anticancer compounds can be alleviated.

Effect of various classes of pesticides on expression of stress genes in transgenic C. elegans model of Parkinson's disease.

Neurodegenerative diseases are known to be associated with genetic and environmental factors. The multifactorial Parkinson's disease (PD) is triggered and/or further worsened by exposure to certain pesticides. Existing literature suggests a link between pesticide exposure and increased incidence of PD. We carried out the present study to look into the stress gene expression pattern of transgenic Caenorhabditis elegans (C. elegans) model of PD after exposure to pesticides from different classes. Expression level of sod-1, sod-2, sod-3, hsp-70, hsp-60, and hsp-16.2 stress responsive genes was determined using qPCR. Our findings demonstrate that the expression of stress related genes does not follow a generalized pattern to different toxicants; rather each pesticide class has a specific expression signature.