Adam Hermawan

Combinational effects of hexane insoluble fraction of Ficus septica Burm. F. and doxorubicin chemotherapy on T47D breast cancer cells

OBJECTIVE To evaluate the effects of n-hexane insoluble fraction (HIF) of Ficus septica leaves in combination with doxorubicin on cytotoxicity, cell cycle and apoptosis induction of breast cancer T47D cell lines. METHODS The in vitro drugs-stimulated cytotoxic effects were determined using MTT assay. Analysis of cell cycle distribution was performed using flowcytometer and the data was analyzed using ModFit LT 3.0 program. Apoptosis assay was carried out by double staining method using ethydium bromide-acridin orange. The expression of cleaved-poly (ADP-ribose) polymerase (PARP) on T47D cell lines was identified using immunocytochemistry. RESULTS The combination exhibited higher inhibitory effect on cell growth than the single treatment of doxorubicin in T47D cells. In addition, combination of doxorubicin and HIF increased the incidence of cells undergoing apoptosis. HIF could improve doxorubicin cytotoxic effect by changing the accumulation of cell cycle phase from G2/M to G1 phase. The combination also exhibited upregulation of cleaved-PARP in T47D cells. CONCLUSIONS Based on this results, HIF is potential to be developed as co-chemotherapeutic agent for breast cancer by inducing apoptosis and cell cycle arrest. However, the molecular mechanism need to be explored further.

Cardioprotective and hepatoprotective effects of Citrus hystrix peels extract on rats model

OBJECTIVE To observe the combination effect of doxorubicin and Citrus hystrix (kaffir limes) peel ethanolic extract (ChEE) on blood serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity and cardio-hepato-histopathology of female Sprague Dawley rats. METHODS Doxorubicin and ChEE (5 rats per group) were administered in five groups of 3 rats each for 11 d. Group I: doxorubicin (dox) 4.67 mg/kg body weight; Group II: dox+ChEE 500 mg/kg body weight; Group III: dox+ChEE 1 000 mg/kg body weight; Group IV: ChEE 1 000 mg/kg body weight; Group V: untreated (control). RESULTS ChEE repaired cardiohistopathology profile of doxorubicin induced cardiotoxicity and hepatotoxicity rats, but did not repair neither hepatohistopathology profile nor reduce serum activity of ALT and AST. CONCLUSION ChEE has potency to be developed as cardioprotector agent in chemotherapy.

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 hexane insoluble fraction of ficus septica burm.F. In doxorubicin-treated rats

The use of chemotherapeutics induces cardiotoxicity and affects immune functions, therefore development of combinatorial agents against cardiotoxicity and immunosuppression needs to be explored. Previous studies of the hexane insoluble fraction (HIF) of an ethanolic extract of Ficus septica leaves showed anticancer effects singly and in combination with doxorubicin on T47D breast cancer cells. In this present study, it was evaluated for its immunomodulatory activities in doxorubicin-treated rats. Thirty male Sprague Dawley rats were divided into five groups consisting of six rats each as follows: Group 1, receiving oral saline 10 ml/kg BW (control group); Group 2, receiving HIF dose 750 mg/kg BW orally, once daily; Group 3, receiving HIF dose 1.500 mg/kg BW orally, once daily; Group 4, given oral saline 10 ml/kg BW (normal group); Group 5, receiving HIF dose 1.500 mg/kg BW orally, once daily. The rats of group 1-3 were intramuscularly administered with doxorubicin at a dose of 4.67 mg/kg BW at the days 1 and 4 to suppress immune functions. Concomitantly, the rats were treated with saline or HIF for seven consecutive days (1 to 7). Treatment of HIF succeeded in reducing side effects of doxorubicin based on increasing lymphocyte density and phagocytosis activity and capacity of macrophages, as well as increasing the CD8+blood level and decreasing spleen IL-10 expression. Hexane insoluble fraction of of ethanolic extract of Ficus septica leaves has potential as a protective agent combined with doxorubicin.

Hesperidin increase cytotoxic effect of doxorubicin in MCF-7 cells

Hesperidin, a flavonoid, shows strong cytotoxic effect in several cancer cell lines. The aim of this research was to investigate cytotoxic activities of hesperidin alone and in combination with doxorubicin. Cell viability assay of hesperidin, doxorubicin, and combination treatments were carried out by using MTT assay. Apoptosis assay was done using double staining method using Ethidium Bromide-Acridine Orange. Hesperidin did not show cytotoxic effect but doxorubicin showed cytotoxic effect with IC50 467 nM. Hesperidin (5, 50 and 100 μM) increased cytotoxic effect of doxorubicin compared with doxorubicin alone. The strongest cytotoxic activity was showed by the combination of 200 nM doxorubicin and 100 μM hesperidin. Combination treatment of doxorubicin 200 nM and hesperidin 100 μM induced apoptosis in MCF-7 cells. Hesperidin is potentially to be developed as co-chemotherapeutic agent for breast cancer, while molecular mechanism need to be explored.

Current report of natural product development against breast cancer stem cells

Chemotherapeutic agents are commonly used as neoadjuvant for breast cancer therapy. However, there is evidence of treatment failure for most of patients due to acquired resistance. Cancer stem cells, a small population of cells within tumors, contribute to cancer resistance, tumor relapse, and metastasis. Therefore breast cancer stem cells-targeted therapy is a strategic way of overcoming chemoresistance. Some natural products have been identified to target breast cancer stem cells. This article aims to discuss the current report of preclinical studies of natural products i.e., phytochemicals, compound isolated from mushroom and alkaloid from the sponge that target breast cancer stem cells. This review does not only describe biological effects of natural products i.e., its effect on the signaling pathway, but also discuss chemical structure modification as well as recent pharmaceutical technology of natural products to target breast cancer stem cells. In conclusion, those natural products posses as novel therapeutic agents for breast cancer stem cells eradication and lead compound for the development of breast cancer stem cells-targeted drug.