A serine/threonine protein PIM kinase as a biomarker of cancer and a target for anti-tumor therapy.

The PIM Kinases belong to the family of a proto-oncogene that essentially phosphorylates the serine/threonine residues of the target proteins. They are primarily categorized into three types PIM-1, PIM-2, PIM-3 which plays an indispensable regulatory role in signal transduction cascades, by promoting cell survival, proliferation, and drug resistance. These kinases are overexpressed in several solid as well as hematopoietic tumors which supports in vitro and in vivo malignant cell growth along with survival by regulating cell cycle and inhibiting apoptosis. They lack regulatory domain which makes them constitutively active once transcribed. PIM kinases usually appear to be important downstream effectors of oncoproteins which overexpresses and helps in mediating drug resistance to available agents, such as rapamycin. Structural studies of PIM kinases revealed that they have unique hinge regions where two Proline resides and makes ATP binding unique, by offering a target for an increasing number of potent PIM kinase inhibitors. Preclinical studies of those inhibitory compounds in various cancers indicate that these novel agents show promising activity and some of them currently being under examination. In this review, we have outlined PIM kinases molecular mechanism and signaling pathways along with matriculation in various cancer and list of inhibitors often used.

An in vivo and in vitro potential of Indian ayurvedic herbal formulation Triphala on experimental gouty arthritis in mice.

In the present study, we have investigated the efficacy of Indian ayurvedic herbal formulation Triphala on monosodium urate crystal-induced inflammation in mice; an experimental model for gouty arthritis and compared it with that of the non-steroidal anti-inflammatory drug, Indomethacin. The anti-arthritic effect of Triphala was evaluated by measuring changes in the paw volume, lysosomal enzyme activities, lipid peroxidation, anti-oxidant status and inflammatory mediator TNF-alpha in control and monosodium urate crystal-induced mice. The levels of beta-glucuronidase and lactate dehydrogenase were also measured in monosodium urate crystal-incubated polymorphonuclear leucocytes (PMNL). Triphala treatment (1 gm/kg/b.w. orally) significantly inhibited the paw volume and the levels of lysosomal enzymes, lipid peroxidation and inflammatory mediator tumour necrosis factor-alpha; however the anti-oxidant status was found to be increased in plasma, liver and spleen of monosodium urate crystal-induced mice when compared to control mice. In addition, beta-glucuronidase and lactate dehydrogenase level were reduced in Triphala (100 microg/ml) treated monosodium urate crystal-incubated polymorphonuclear leucocytes. In conclusion, the results obtained clearly indicated that Triphala exerted a strong anti-inflammatory effect against gouty arthritis.

Antiinflammatory effect of the Indian Ayurvedic herbal formulation Triphala on adjuvant-induced arthritis in mice.

In the present study, attempts have been made to evaluate the antiarthritic effect of the Indian Ayurvedic herbal formulation Triphala on adjuvant-induced arthritis in mice and to compare it with that of the non-steroidal antiinflammatory drug indomethacin. Arthritis was induced by intradermal injection of complete Freund's adjuvant (0.1 mL) into the right hind paw of Swiss albino mice. Triphala (1 g/kg/bxwt) and indomethacin (3 mg/kg/bxwt) were administered orally for 8 days (from day 11 to 18) after adjuvant injection. The levels of lysosomal enzymes, tissue marker enzymes, glycoproteins and paw thickness were increased in adjuvant-induced arthritic animals. The body weight was found to be reduced when compared with the control animals. These physical and biochemical changes observed in arthritic animals were altered significantly to near normal conditions after oral administration of Triphala (1 g/kg/bxwt). The results obtained clearly indicate the fact that the Indian Ayurvedic herbal formulation Triphala has promising antiinflammatory activity.