No abstract

Tangeretin, shows cytotoxic effect on COLO 205 colon cancer cells. Combination of tangeretin with tamoxifen showed synergistic effect and increased the cancer cell sensitivity towards tamoxifen on T47D cells. However, the combination of tangeretin with chemotherapeutic agent doxorubicin on breast cancer cells have not been explored yet. Therefore, the aim of this research is to examine the improvement of cytotoxic effect of doxorubicin by tangeretin through cell death induction and cell cycle modulation on MCF-7 and T47D cells. The cytotoxic effect of tangeretin, doxorubicin, and their combination on tested cells were carried out by using MTT assay. Cell cycle distribution was determined by flowcytometer FACSCalibur and the flowcytometry data was analyzed using ModFit LT 3.0 program. Cell death assay were done by double staining method using ethydium bromide-acridin orange. Single treatment of tangeretin 5-100 μM did not show cytotoxic effect on MCF-7 and T47D cells. The combination of tangeretin 50 and 100 μM with doxorubicin 200 nM (MCF-7) and 7.5 nM (T47D) increased the cytotoxic effect of doxorubicin on both breast cancer cell lines. This improvement of cytotoxic effect is due to cell death induction and cell cycle modulation. Furthermore, single treatment of tangeretin showed cell death only on T47D cell and caused G1-phase arrest on MCF-7 cell and G2/M-phase arrest on T47D cell. While doxorubicin induced cell accumulation at G2/M phase in both cancer cell lines. However, combination of tangeretin and doxorubicin increased cell death on both cancer cell lines, compared with doxorubicin by itself. The combination also showed G1-phase arrest on MCF-7 cell and increased cell accumulation at G2/M phase on T47D cell. Based on this result, tangeretin is potential to be developed as cochemotherapeutic agent for breast cancer by inducing apoptosis and cell cycle arrest. However, the molecular mechanism need to be explored further.

Therapy of colon cancer by using 5-FU often causes problems of resistance. This encourages the development of co-chemotherapy agent. One of the compounds that could potentially be used as a co-chemotherapy agent is hesperidin. This study was conducted to determine the cytotoxic effects of hesperidin, 5-FU and the combination of them, as well as apoptosis induction in colon cancer cells WiDr. Cytotoxic effect of hesperidin, 5-FU, and its combination were observed using MTT assay. Observation of apoptosis was done by double staining method using ethidium bromide-acridin orange. Until 48 hours incubation, hesperidin showed no cytotoxic effects. Cytotoxic effects of 5-FU was observed after 48 hours with the IC50 value of 422 µM. However, hesperidin improved the cytotoxic effects of 5-FU at 48 hour incubation. Either single treatment of hesperidin 200µM or 5-FU 1500 µM did not trigger apoptosis, but combination of them led to the emergence of signs of apoptosis. Based on this study,it can be concluded thathesperidin is potential to be developed as a co-chemotherapy agent of 5-FU on colon cancer but still need further study on its molecular mechanisms.Keywords : hesperidin, 5-fluorouracil, WiDr cells, cytotoxic, apoptosis

The prognosis of breast cancer patients is closely associated with the response of tumor cells to chemotherapy agent. Doxorubicin is one of the primary chemotherapeutic agents used for the treatment of breast cancer. Resistance to chemotherapy is believed to cause treatment failure in cancer patients. Furthermore, long time exposure to chemotherapeutic agent induces cancer cells resistance. MCF-7 sensitive cells used as chemoresistance model have overexpression P-gp (P-glycoprotein). Chemoresistance was established by treating MCF-7 cells with 0.5 µg/ml doxorubicin-contained medium for a week. 50% inhibiting concentration (IC50) doxorubicin on MCF-7 cells/DOX were determined using MTT assay. Western blot assay and immunocytochemistry assay was performed to determine the expression of P-gp. Morphological of MCF-7 cell/DOX was changing to become larger and have lamellapodia. IC50 value of doxorubicin was 700 nM on MCF-7/DOX and 400 nM on sensitive MCF-7 cells. The MCF-7/DOX sensitivity to doxorubicin was decreased, shown by 1.5 fold higher IC50 of doxorubicin on MCF-7/DOX compared to MCF-7 sensitive cells. Treatment doxorubicin to sensitive MCF-7 cells leads to the increasing P-gp expression. The P-gp level expression has strong correlation with the low sensitivity of MCF-7/DOX to doxorubicin.Keywords: doxorubicin, resistance cells, sensitive MCF-7 cell

Celery (Apium graveolens L.) is commonly used to lower blood pressure, antirheumatic, relaxant, mild diuretic, antiseptic for the urinary tract, antioxidant, and anti-inflammation. According to previous studies, a number of the phytochemicals found in the plant show cytotoxicity toward some types of cancer cells. However, studies on the cytotoxic effects of celery herb ethanolic extract (CEE) on breast cancer cell (T47D), colon cancer cell (WiDr), and cervix cancer cell (HeLa), however, has not been done yet. Our research aims at doing so. Cytotoxicity test was conducted using MTT assay and its absorbance was read using ELISA reader at λ = 595 nm. Results of the assay show that CEE reduces cell viability at concentrations of 100-750 µg/ml on HeLa cells, while reduction of T47D and WiDr cell viability was not achieved until concentrations of 500-750 µg/ml. Based on these results, we conclude that CEE hold many potentials for further developments as preventive and therapeutive agent in cancer treatment.