Retno Murwanti

Curcumin and its analogues (PGV-0 and PGV-1) enhance sensitivity of resistant MCF-7 cells to doxorubicin through inhibition of HER2 and NF-kB activation.

Chemoresistance of breast cancer to doxorubicin is mediated mainly through activation of NF-kB and over expression of HER2. Curcumin and its analogues (PGV-0 and PGV-1) exert cytotoxic effects on T47D breast cancer cells. Suppression of NF-kB activation is suggested to contribute to this activity. The present study aimed to explore the effects of curcumin, PGV-0, and PGV-1 singly and in combination with doxorubicin on MCF-7/Dox cells featuring over-expression of HER2. In MTT assays, curcumin, PGV-0, and PGV-1 showed cytotoxicity effects against MCF-7/Dox with IC50 values of 80 μM, 21 μM, and 82 μM respectively. These compounds increased MCF-7/Dox sensitivity to doxorubicin. Cell cycle distribution analysis exhibited that the combination of curcumin and its analogues with Dox increased sub G-1 cell populations. Curcumin and PGV-1 but not PGV-0 decreased localization of p65 into the nucleus induced by Dox, indicating that activation of NF- kB was inhibited. Molecular docking of curcumin, PGV-0, and PGV-1 demonstrated high affinity to HER2 at ATP binding site. This interaction were directly comparable with those of ATP and lapatinib. These findings suggested that curcumin, PGV-0 and PGV-1 enhance the Dox cytotoxicity to MCF-7 cells through inhibition of HER2 activity and NF-kB activation.

Antiproliferative effect of gynura procumbens (lour.) Merr. Leaves etanolic extract on 7,12-dimethylbenz(a)antracene induced male rat liver

PURPOSE The leaves of Gynura procumbens (Lour.) Merr. has been traditionally used as anticancer. Ethanolic extract of G. procumbens leaves (EGP) showed cytotoxic activity and anticancer activity in animal cancer model. This study was conducted to observe antiproliferative effect using male rats liver cells induced by 7,12-dimethylbenz(a)antracene (DMBA). METHODS Forty days old Sprague Dawley male rats were divided into 4 groups, (1) 0.5 % CMC Na, (2) 20 mg/kg BW DMBA p.o ten times in three weeks, (3) DMBA+300 mg/kg BW of EGP, and (4) DMBA+750 mg/kg BW of EGP. The extract was dissolved into 0.5 % CMC-and administered daily per oral one week before, during and terminated 1 week after the DMBA induction. After sixthteen week experiment, rat livers were sectioned and stained with Haematoxyllene and Eosin (H&E) and AgNOR. RESULTS Histopatology profile showed no primary liver tumor on DMBA group. mAgNOR value of DMBA+300 mg/kg BW EGP showed significant antiproliferative effect compared to DMBA group. CONCLUSION Ethanolic extract of G. procumbens leaves showed antiproliferative activity on male rats liver induced by DMBA.

Immunomodulatory Effects of Ethanolic Extract of Thyphonium flagelliforme (Lodd) Blume in Rats Induced by Cyclophosphamide

The present study aimed to examine the immunomodulatory effect of ethanolic extract of Typhonium flagelliforme (Lodd) Blume in cyclophosphamide-treated rats. The immunomodulatory effects were determined by lymphocytes proliferation, phagocytic activity of macrophages, plasma cytokines of tumor necrosis factor-α, interleukin-1α, interleukin-10 levels, and killer T cells (CD8+ T cells) counts. The results showed that the administration of ethanolic extract of T flagelliforme reduced immunosupessive effect on lymphocyte proliferation, increase the number and phagocytic activity of macrophages in cyclophosphamide-treated rats. Moreover, the ethanolic extract of T flagelliforme also significantly (P < .05) improved the immune system activities especially the proliferation of CD8+T cells and reduced the suppressive effects on cytokines such as tumor necrosis factor-α and interleukin-1α. In conclusion, the ethanolic extract of T flagelliforme has immunomodulatory properties in cyclophosphamide-treated rats. The results suggest that T flagelliforme can reduce immunosuppresive effect caused by a chemotherapeutic agent.