Antioxidants as precision weapons in war against cancer chemotherapy induced toxicity - Exploring the armoury of obscurity.

Cancer is the leading cause of mortality worldwide, accounting for almost 13% of deaths in the world. Among the conventional cancer treatments, chemotherapy is most frequently carried out to treat malignant cancer rather than localised lesions which is amenable to surgery and radiotherapy. However, anticancer drugs are associated with a plethora of side effects. Each drug, within every class, has its own set of adverse reactions which may cause patient incompliance and deterioration of the quality of life. One of the major causes of adverse reactions, especially for drugs targeting DNA, is the excessive production of reactive oxygen species (ROS) and subsequent build up of oxidative stress. To curb these undesired side effects, several dietary supplements have been tested, amongst which antioxidants have gained increasing popularity as adjuvant in chemotherapy. However, many oncologists discourage the use of antioxidant rich food supplements because these may interfere with the modalities which kill cancer by generating free radicals. In the present review, all studies reporting concomitant use of several antioxidants with chemotherapy are indiscriminately included and discussed impartially. The effect of supplementation of thirteen different antioxidants and their analogues as a single agent or in combination with chemotherapy has been compiled in this article. The present review encompasses a total of 174 peer-reviewed original articles from 1967 till date comprising 93 clinical trials with a cumulative number of 18,208 patients, 56 animal studies and 35 in vitro studies. Our comprehensive data suggests that antioxidant has superior potential of ameliorating chemotherapeutic induced toxicity. Antioxidant supplementation during chemotherapy also promises higher therapeutic efficiency and increased survival times in patients.

Exploring the effect of vitamin E in cancer chemotherapy-A biochemical and biophysical insight.

Many oncologists contend that patient undergoing chemotherapy must avoid antioxidant supplementation as it may interfere with the activity of the drug. In the present investigation, we have explored the influence of vitamin E, a well-known antioxidant on Camptothecin (CPT), a potent anti-cancer drug induced cell apoptosis and death of cervical cancer cells. HeLa cells were treated with different concentrations of CPT in presence and absence of 100 µm vitamin E. Treated cells were subjected to cytotoxicity studies, catalase assay, DNA fragmentation assay, clonogenic assay and flow cytometry based apoptosis detection. Also, Raman spectroscopy a label free technique which provides global information, in conjunction with multivariate tools like PCA, PCLDA and FDA, was investigated to explore vitamin E supplementation induced alterations. Our data based on biochemical and biophysical experimental analysis reveals that CPT causes DNA damage along with protein and lipid alteration culminating in cell death. Importantly, Raman spectroscopic analysis could uniquely differentiate the cluster of control and vitamin E control from CPT and CPT + Vit E treated cells. We conclusively prove that presence of vitamin E at 100 µM concentration shows promising antioxidant activity and displays no modulatory role on CPT induced effect, thereby causing no possible hindrance with the efficacy of the drug. Vitamin E may prove beneficial to alleviate chemotherapy associated side effects in patients during clinical settings which may open the doors further for subsequent exploration in in vivo preclinical studies.

Milk-derived multi-fluorescent graphene quantum dot-based cancer theranostic system.

An economical green-chemistry approach was used for the synthesis of aqueous soluble graphene quantum dots (GQDs) from cow milk for simultaneous imaging and drug delivery in cancer. The GQDs synthesized using one-pot microwave-assisted heating were multi-fluorescent, spherical in shape having a lateral size of ca. 5nm. The role of processing parameters such as heating time and ionic strength showed a profound effect on photoluminescence properties of GQDs. The GQDs were N-doped and oxygen-rich as confirmed by X-ray photoelectron spectroscopy (XPS) analysis. Cysteamine hydrochloride (Cys) was used to attach an anti-cancer drug berberine hydrochloride (BHC) on GQDs forming GQDs@Cys-BHC complex with c.a. 88% drug loading efficiency. In vitro drug release was studied at the acidic-basic environment and drug kinetics was studied using pharmacokinetic statistical models. The GQDs were biocompatible on L929 cells whereas theranostic GQDs@Cys-BHC complex showed a potent cytotoxic effect on different cancerous cell line models: cervical cancer cell lines such as HeLa cells and breast cancer cells such as MDA-MB-231 confirmed by Trypan blue and MTT-based cytotoxic assays. Furthermore, multi-excitation based cellular bioimaging was demonstrated using confocal laser scanning microscopy (CLSM) and fluorescence microscopy using GQDs as well as GQDs@Cys-BHC complex. Thus, drug delivery (therapeutic) and bioimaging (diagnostic) properties of GQDs@Cys-BHC complex are thought to have a potential in vitro theranostic application in cancer therapy.

An in vitro study of the ameliorative role of α-tocopherol on methotrexate-induced oxidative stress in rat heart mitochondria.

BACKGROUND: Methotrexate (MTX) is a folic acid antagonist widely used as a cytotoxic chemotherapeutic agent for many malignancies. Its use is limited due to wide-ranging toxicities. MTX generates reactive oxygen species. Here, we investigated the efficacy of vitamin E supplementation on MTX-induced alterations in vitro. METHODS: Rat heart mitochondria were isolated and used to assess the extent of swelling, lipid peroxidation and alterations in mitochondrial-specific enzyme activities caused by the addition of 80 µM MTX in the presence and absence of 1.2 µM vitamin E. Control for both groups was maintained. RESULT: MTX substantially affects mitochondrial function by increasing lipid peroxidation and mitochondrial swelling. Significant losses in the activities of the tricarboxylic acid cycle enzymes, complex I, II and IV, and an increase in the activity of calcium ATPase were observed in MTX-treated rat mitochondria. Enrichment of the media with vitamin E led to a reduction in swelling and restoration of enzyme activities. CONCLUSIONS: The present study suggests that vitamin E plays a vital role in suppressing MTX-induced mitochondrial toxicity, and affords protection either by reversing the decline of antioxidants or by direct scavenging of free radicals.