Nerolidol assists Cisplatin to induce early apoptosis in human laryngeal carcinoma Hep 2 cells through ROS and mitochondrial-mediated pathway: An in vitro and in silico view.

The objective of this study was to examine Nerolidol (NER) and Cisplatin (CIS) performed against human laryngeal carcinoma (Hep 2) cells. We evaluated the effect of NER, CIS, and NER + CIS on cell viability, cell migration, oxidative stress, mitochondrial membrane depolarization, nuclear condensation, apoptotic induction, and DNA damage in Hep 2 cells. We used the MTT assay to assess the cytotoxicity effect of NER and CIS on Hep 2 cells in terms of morphological alterations. Present results demonstrated that IC50 values of NER and CIS have potential cytotoxicity against Hep 2 cells. NER effectively inhibited cell viability, increased reactive oxygen species generation, apoptotic induction, and DNA damage in Hep 2 cells. In addition, the docking study evaluated the structural binding interaction of NER with PI3K/Akt and PCNA protein. Furthermore, NER with PI3K/Akt, PCNA has a higher crucial score and affinity. Present results infer that NER could be used to target signaling molecules in anticancer studies. PRACTICAL APPLICATIONS: Nerolidol is a dietary phytochemical with high biological activity that can find in a variety of plants. Many researchers focused on Nerolidol to treat various diseases including cancer. However, there is no studies exist on laryngeal cancer. This study uses Nerolidol and Cisplatin to generate oxidative stress and stimulate apoptosis and DNA damage in human laryngeal cancer cells. Based on present findings, Nerolidol could be a choice of anticancer medication, either alone or in combination against oral squamous cell carcinomas in both in vitro and in vivo experimental systems.

Anticancer and antioxidant profiling effects of Nerolidol against DMBA induced oral experimental carcinogenesis.

The objective of this study is to examine the chemopreventive effects of Nerolidol (NER) on hamster buccal pouch carcinogenesis (HBC) induced by 7,12-dimethylbenz(a)anthracene (DMBA) in male golden Syrian hamsters. In this study, oral squamous cell carcinoma was developed in the buccal pouch of an oral painted hamster with 0.5% DMBA in liquid paraffin three times weekly for 12 weeks. To assess DMBA-induced hamster buccal tissue carcinogenesis, biochemical endpoints such as Phase I and II detoxification enzymes, antioxidants, lipid peroxidation (LPO) by-products, and renal function markers, as well as histopathological examinations, were used. Furthermore, the immunohistochemical studies of interleukin-6 were investigated to find the inflammatory link in the HBC carcinogenesis. In our results, DMBA alone exposed hamsters showed 100% tumor growth, altered levels of antioxidants, detoxification agents, LPO, and renal function identifiers as compared to the control hamsters. The outcome in  present biochemical, histopathological, and immunohistochemistry studies has been found a reverse in NER-treated hamsters against the tumor. This study concluded that NER modulated the biochemical profiles (antioxidants, detoxification, LPO, and renal function markers) and inhibited tumor development in DMBA induced oral carcinogenesis.

Mitochondria Associated Membranes (MAMs): Emerging Drug Targets for Diabetes.

MAMs, the physical association between the Endoplasmic Reticulum (ER) and mitochondria are, functional domains performing a significant role in the maintenance of cellular homeostasis. It is evolving as an important signaling center that coordinates nutrient and hormonal signaling for the proper regulation of hepatic insulin action and glucose homeostasis. Moreover, MAMs can be considered as hot spots for the transmission of stress signals from ER to mitochondria. The altered interaction between ER and mitochondria results in the amendment of several insulin-sensitive tissues, revealing the role of MAMs in glucose homeostasis. The development of mitochondrial dysfunction, ER stress, altered lipid and Ca2+ homeostasis are typically co-related with insulin resistance and ß cell dysfunction. But little facts are known about the role played by these stresses in the development of metabolic disorders. In this review, we highlight the mechanisms involved in maintaining the contact site with new avenues of investigations for the development of novel preventive and therapeutic targets for T2DM.

Preventive effect of D-carvone during DMBA induced mouse skin tumorigenesis by modulating xenobiotic metabolism and induction of apoptotic events.

The structural integrity and excellent immune system of the skin makes it a protective covering, inspite of its exposure to hazardous compounds. In the present study, the chemopreventive efficacy of D-carvone was studied in 7, 12-dimethylbenz[a]anthracene (DMBA) induced skin carcinogenesis. DMBA (25 µg in 0.1 m L-1acetone) was used to induce skin cancer in Swiss albino mice. Animals were randomly divided into six groups of six animals in each. Different concentrations of D-carvone (10, 20, 30 mg/kg body weight) were used to assess its anticancer effect. Tumor incidence, tumor volume, tumor burden, histological examination and levels of phase I and phase II detoxification agents were analyzed in experimental animals. Further, expression of p53 and various apoptotic proteins including- Bcl-2, Bax was analyzed using immunohistochemistry and enzymatic expression of apoptotic proteins caspase-3 and caspase-9 was carried out by using ELISA. We observed 100% tumor incidence in DMBA-painted animals and our results showed that D-carvone at 20 mg dose significantly prevents skin carcinogenesis. Our results also showed decreased levels of phase I enzymes (Cyt P450 and-Cyt b5) with increased levels of phase II enzymes (GR, GST and GSH) and increased expression of Bax, caspase-3 and caspase-9 with decreased expression of mutated p53 and Bcl-2 in animals treated with DMBA and D-carvone at 20 mg dose. The results of the present study suggest that D-carvone can be used as a chemopreventive agent against skin cancer, as it induces apoptosis in cancer. However, further studies are warranted to check chemopreventive efficacy of D-carvone on cell proliferation, angiogenesis, and metastasis before going to human trial.