Inhibition of the JAK-STAT3 Pathway by Andrographolide Enhances Chemo-Sensitivity of Cancer Cells to Doxorubicin

Biochem Pharmacol. 2009 Dec 17. [Epub ahead of print]

Inhibition of the JAK-STAT3 Pathway by Andrographolide Enhances
Chemo-Sensitivity of Cancer Cells to Doxorubicin.

Zhou J, Ong CN, Hur GM, Shen HM.

Department of Epidemiology and Public Health, Yong Loo Lin School of
Medicine, Republic of Korea.

Andrographolide (Andro), a diterpenoid lactone isolated from a
traditional herbal medicine Andrographis paniculata, is known to
possess potent anti-inflammatory and anticancer property. In this
study, we sought to examine the effect of Andro on Signal Transducer
and Activator of Transcription 3 (STAT3) pathway and evaluate whether
suppression of STAT3 activity by Andro could sensitize cancer cells to
a chemotherapeutic drug doxorubicin. First, we demonstrated that Andro
is able to significantly suppress both constitutively activated and
IL-6-induced STAT3 phosphorylation and subsequent nuclear
translocation in cancer cells. Such inhibition is found to be achieved
through suppression of Janus-activated kinase (JAK)1/2 and interaction
between STAT3 and gp130. For understanding the biological significance
of the inhibitory effect of Andro on STAT3, we next investigated the
effect of Andro on doxorubicin-induced apoptosis in human cancer
cells. In our study the constitutive activation level of STAT3 was
found to be correlated to the resistance of cancer cells to
doxorubicin-induced apoptosis. Both the short-term MTT assay and the
long-term colony formation assay showed that Andro dramatically
promoted doxorubicin-induced cell death in cancer cells, indicating
that Andro enhances the sensitivity of cancer cells to doxorubicin
mainly via STAT3 suppression. These observations thus reveal a novel
anti-cancer function of Andro and suggest a potential therapeutic
strategy of using Andro in combination with chemotherapeutic agents
for treatment of cancer. Copyright © 2009. Published by Elsevier Inc.

PMID: 20026083 [PubMed - as supplied by publisher]

Efficacy of botanical extracts against Japanese encephalitis vector, Culex tritaeniorhynchus

Parasitol Res. 2009 Dec 2. [Epub ahead of print]

Efficacy of botanical extracts against Japanese encephalitis vector, Culex tritaeniorhynchus.

Elango G, Rahuman AA, Bagavan A, Kamaraj C, Zahir AA, Rajakumar G, Marimuthu S, Santhoshkumar T.

Unit of Bioactive Natural Products, Post Graduate and Research Department of Zoology, C. Abdul Hakeem College, Melvisharam, 632 509, Vellore District, Tamil Nadu, India.

The purpose of the present study was to assess the effect of leaf hexane and chloroform extracts of Aegle marmelos, Andrographis lineata, Andrographis paniculata, Cocculus hirsutus, Eclipta prostrata, and Tagetes erecta on repellent, ovicidal, and oviposition-deterrent activities against Culex tritaeniorhynchus Giles (Diptera: Culicidae). The repellent action of the plant extracts tested varied depending on the plant species, part, solvent used in extraction, and the extract dose. The hexane extract of A. paniculata was more effective in exhibiting the repellent action against the mosquito as compared with A. lineata extract. Complete protections for 150 min were found in hexane extract of A. paniculata at 500 ppm against mosquito bites. Mean percent hatchability of the ovicidal activity was observed 24 h after treatment. The percent hatchability was inversely proportional to the concentration of extract and directly proportional to the eggs. No hatchability was observed with hexane, and chloroform extracts of A. lineata, A. paniculata, and hexane extract of T. erecta were exerted at 1,000 ppm. The percentage of effective oviposition repellency were 95.90, 94.75, 95.04, 90.58, 87.93, 87.14, 94.82, 95.71, 92.26, 90.58, 83.35, and 78.16 at 500 ppm, and the lowest repellency was 69.93, 53.06, 64.81, 70.06, 51.82, 54.54, 48.31, 66.71, 68.82, 61.85, 34.84, and 39.53 at 31.25 ppm in hexane and chloroform extracts of A. marmelos, A. lineata, A. paniculata, C. hirsutus, E. prostrata, and T. erecta, respectively. The oviposition activity index values revealed that the solvent plant extracts have deterrent effect, and they caused a remarkable negative response resulting in oviposition of very few eggs. These results clearly reveal that the hexane extracts of A. marmelos and A. paniculata served as a potential repellent, ovicidal, and oviposition deterrent against Japanese encephalitis vector, C. tritaeniorhynchus.

PMID: 19953270 [PubMed - as supplied by publisher]