Sankar Pajaniradje

Bio: Sankar Pajaniradje is an academic researcher from Pondicherry University. The author has contributed to research in topics: Curcumin & Apoptosis. The author has an hindex of 8, co-authored 13 publications receiving 225 citations.

Antiproliferative and Apoptotic Effects of Sesbania grandiflora Leaves in Human Cancer Cells

Abstract: Natural phytochemicals and their derivatives are good drug candidates for anticancer therapeutic approaches against multiple targets We report here the initial findings from our studies on the anticancer properties of the leaves of the medicinal plant Sesbania grandiflora In the current study, five different solvent fractions from the leaves of S grandiflora were tested on cancer cell lines such as MCF-7, HepG2, Hep-2, HCT-15, and A549 The methanolic fraction of S grandiflora was found to exert potent antiproliferative effects especially in the human lung cancer cell line, A549 Caspase 3 was activated in the methanolic fraction treated A549 cells thereby leading to cell death by apoptosis DAPI staining, DNA laddering, and decrease in mitochondrial membrane potential further confirmed the apoptotic mode of cell death The high levels of ROS intermediates as evidenced by DCF-DA staining could have played a role in the apoptotic induction Decrease in levels of cyclin D1 and decrease in the activation of NFkB were observed in A549 cells on treatment with methanolic fraction, giving a hint on the possible mechanism of action These results prove that the medicinal plant S grandiflora can be explored further for promising candidate molecules to combat cancer, especially lung cancer

Apoptosis induction by an analog of curcumin (BDMC-A) in human laryngeal carcinoma cells through intrinsic and extrinsic pathways

Abstract: Head and neck cancer is the sixth most frequently occurring cancer worldwide and accounts for about 2 % of all cancer-related deaths annually. Curcumin is a well-known chemopreventive agent, and apoptosis induction by curcumin has been reported in many cancer cell types. We synthesized an ortho-hydroxy substituted analog of curcumin, bisdemethoxycurcumin analog (BDMC-A), and aimed to demarcate the apoptotic effects induced by BDMC-A on human laryngeal cancer Hep-2 cells and to compare these effects with those induced by curcumin. We evaluated the apoptotic effects of BDMC-A in comparison to those of curcumin on Hep-2 cells by performing Western blotting, RT-PCR, fluorescent staining and DNA fragmentation assays. In addition, we carried out an in silico molecular docking study on the EGFR kinase domain. We found that BDMC-A can induce apoptosis in Hep-2 cells by regulating the expression of both intrinsic and extrinsic apoptotic proteins, i.e., Bcl-2, Bax, apoptososme complex and death receptors, more efficiently than curcumin. We also observed increased nuclear fragmentation and chromatin condensation after BDMC-A treatment compared to curcumin treatment. Depolarized mitochondria and ROS generation was well pronounced in both BDMC-A and curcumin treated Hep-2 cells. Our in silico molecular docking study on the EGFR kinase domain revealed that BDMC-A may dock more efficiently than curcumin. From our results we conclude that BDMC-A can induce apoptosis in Hep-2 laryngeal carcinoma cells more effectively than curcumin, and that this activity can be attributed to the presence of a hydroxyl group at the ortho position within this compound.

A Nanoparticle Size Series for In Vivo Fluorescence Imaging

Abstract: Any design of nanoparticle vectors for cancer therapy or imaging must take into account the interaction of the nanoparticles with the tumor microenvironment. Size, charge, and shape have been shown to dominate this interaction.[1, 2] In vivo probing of solid tumors with particles of different sizes simultaneously has thus far been challenging due to the limitations of available nano-sized probes.[3–5] Fluorescent dextrans and other macromolecule probes have been used in studies with intravital microscopy, but heterogeneities across samples has prevented their use for the simultaneous imaging of a size series of probes within the same tumour.[5] MRI contrast agents are another attractive set of probes due to the minimally-invasive nature of the technology,[6, 7] but the lower spatial resolution of MRI limits the imaging of heterogeneity within tumors, and the technique does not allow for simultaneous imaging and tracking of a size series of probes within the same tumor.

Mechanisms of tumour invasion and metastasis : emerging targets for therapy

Abstract: The progression of a tumour from one of benign and delimited growth to one that is invasive and metastatic is the major cause of poor clinical outcome in cancer patients. The invasion and metastasis of tumours is a highly complex and multistep process that requires a tumour cell to modulate its ability to adhere, degrade the surrounding extracellular matrix, migrate, proliferate at a secondary site and stimulate angiogenesis. Knowledge of the process has greatly increased and this has resulted in the identification of a number of molecules that are fundamental to the process. The involvement of these molecules has been shown to relate not only to the survival and proliferation of the tumour cell but, also to the processes of tumour cell adhesion, migration, and the tumour cells ability to degrade and escape the primary site as well as play a role in angiogenesis. These molecules may provide important therapeutic targets that represent the ability to target specific steps in the process of invasion and metastasis and provide additional therapies. The review focuses on representative key targets in each of these processes and summarises the state of play in each case.

Caspase-9 as a therapeutic target for treating cancer.

Abstract: Introduction: Caspase-9 is the apoptotic initiator protease of the intrinsic or mitochondrial apoptotic pathway, which is activated at multi-protein activation platforms. Its activation is believed to involve homo-dimerization of the monomeric zymogens. It binds to the apoptosome to retain substantial catalytic activity. Variety of apoptotic stimuli can regulate caspase-9. However, the mechanism of action of various regulators of caspase-9 has not been summarized and compared yet. In this article, we elucidate the regulators of caspase-9 including microRNAs, natural compounds that are related to caspase-9 and ongoing clinical trials with caspase-9 to better understand the caspase-9 in suppressing cancer.Areas covered: In this study, the basic mechanism of apoptosis pathways, regulators of caspase-9 and the development of drugs to regulate caspase-9 are reviewed. Also, ongoing clinical trials for caspase-9 are discussed.Expert opinion: Apoptosis has crucial role in cancer, brain disease, aging and heart di...

Curcumin enhances the apoptosis-inducing potential of TRAIL in prostate cancer.

Abstract: B85 Tumorigenesis or carcinogenesis is a multi-step process that is induced primarily by carcinogens leading to the development of cancer. Extensive research in the last few years has revealed that regular consumption of certain fruits, vegetables and dietary products can reduce the risk of acquiring cancers. Curcumin (a diferuloylmethane, the yellow pigment in turmeric) possesses inhibitory effects on growth of a variety of tumor cells by reducing cell proliferation and inducing apoptosis. TRAIL induces apoptosis by binding to specific cell surface death receptors (TRAIL-R1/DR4 and TRAIL-R2/DR5). The objectives of this research were to investigate the mechanisms by which curcumin induced apoptosis in prostate cancer cells, and sensitized TRAIL-resistant LNCaP cells. Curcumin induced apoptosis in PC-3 cells and sensitize TRAIL-resistant LNCaP cells. Curcumin inhibited the expression of Bcl-2 and Bcl-XL, and induced the expression of Bax, Bak, PUMA, Bim, and Noxa in PC-3 and LNCaP cells. Treatment of prostate cancer cells with curcumin resulted in generation of reactive oxygen species and drop in mitochondrial membrane potential. Thus, curcumin sensitized TRAIL-resistant LNCaP cells to undergo apoptosis through multiple mechanisms i.e. regulation of Bcl-2 family members, up-regulation of death receptors and engagement of mitochondrial pathway. The ability of curcumin to enhance the apoptosis-inducing potential of TRAIL, and sensitize TRAIL-resistant LNCaP cells suggests that curcumin may induce fundamental alterations in cell signaling pathways leading to apoptosis. Overall, our results suggest that curcumin alone or in combination with TRAIL can be used as promising new candidate for prostate cancer prevention and/or therapy.